共查询到20条相似文献,搜索用时 31 毫秒
1.
Acharya B Shirakawa T Pungky A Damanik P Massi MN Miyata M Matsuo M Gotoh A 《American journal of nephrology》2005,25(1):30-35
BACKGROUND/AIMS: Minimal change nephrotic syndrome (MCNS) in children is frequently associated with allergy and immunoglobulin E (IgE) production. T-helper subtype 2 cytokines, such as interleukin (IL)-4 and IL-13, have been implicated in the regulation of IgE production. We investigated the associations of gene polymorphisms of IL-4, IL-13, and signal transducer and activator 6 (STAT6) in Indonesian children with MCNS (n = 84) and controls with neither allergic nor renal disease (n = 61). METHODS: Polymerase chain reaction-restriction fragment length polymorphism was used to determine the IL-4 promoter gene polymorphism (-590C/T) and IL-13 gene polymorphism (4257G/A), and direct sequencing was used for the STAT6 3S untranslated region (2964G/A) polymorphism. RESULTS: There was a significant difference between the MCNS group and the controls in the genotypic distribution of IL-4 and IL-13 gene polymorphism. In the case of the IL-4 promoter gene, the frequency of the CC homozygote was significantly lower in the MCNS group than in the controls, while, in the case of IL-13, the frequency of the GG homozygote was significantly lower in the MCNS group. However, there was no difference between the MCNS group and the controls in the STAT6 gene polymorphism. CONCLUSION: The genetic variations in the IL-4 and IL-13 genes may be associated with predisposition to MCNS. 相似文献
2.
Chang-Li Wei Wai Cheung Chew-Kiat Heng Novi Arty Samuel S Chong Bee-Wah Lee Ken-Lee Puah Hui-Kim Yap 《Nephrology, dialysis, transplantation》2005,20(4):728-734
BACKGROUND: Minimal-change nephrotic syndrome (MCNS) has been associated with atopy. As interleukin-13 (IL-13) has been implicated in the pathogenesis of MCNS, we postulated that IL-13 genetic polymorphisms could influence either susceptibility or clinical course of the disease. METHODS: Seventy-two Singapore Chinese children with MCNS and 78 normal controls were screened for single nucleotide polymorphisms (SNPs) in the IL-13 gene by direct sequencing. Allele and genotype frequencies of these SNPs were determined and their relationship with different clinical courses was analysed. RESULTS: Six SNPs were identified in the 5' promoter, exon 4 and 3' untranslated region (3'UTR). The three SNPs in the 3'UTR--4738 (G/A), 4793 (C/A) and 4926 (C/T)--were in tight linkage disequilibrium (Delta > or = 0.99). There was no difference in allele or genotype frequencies between MCNS children and normal controls. However, there was a significantly lower frequency of allele 4738G in those MCNS children who were still relapsing after 5 years of follow-up (G = 0.52), compared with those in complete remission (G = 0.72; P<0.05) and normal controls (G = 0.69; P<0.05). Haplotype analysis showed a significantly higher frequency of the GCC haplotype in controls and MCNS patients in complete remission (chi2 = 6.35; P<0.02), while the frequency of AAT haplotype was higher in those MCNS children still relapsing after 5 years of follow-up (chi2 = 5.38; P<0.02). Moreover, peripheral blood mononuclear cell IL-13 mRNA expression in patients with haplotype AAT was significantly higher than in those with haplotype GCC. CONCLUSIONS: These results suggest that genetic polymorphisms in the 3'UTR of the IL-13 gene correlate with long-term outcome of MCNS, rather than disease susceptibility, in Singapore Chinese children. 相似文献
3.
J. Yamaguchi Y. Hasegawa M. Kawasaki T. Masui T. Kanoh N. Ishiguro N. Hamajima 《Osteoporosis international》2006,17(6):908-913
Introduction Osteoporosis is a multifactorial genetic disease which greatly increases the risk of bone fracture in elderly persons.
Methods Four hundred and three recipients of a community health screening program were examined for the presence/absence of osteoporosis
and 11 kinds of gene polymorphisms as a means of determining the relation between these gene polymorphisms and osteoporosis.
The gene polymorphisms screened were: alcohol sensitivity-associated polymorphisms of alcohol dehydrogenase (ADH2) Arg47His,
aldehyde dehydrogenase (ALDH2) Glu487Lys, smoking sensitivity-associated polymorphisms of glutathione S transferase (GST)
M1, (GST)T1, NAD(P)H quinone oxidoreductase 1 (NQO1) C609T, inflammation-associated polymorphisms of interleukin-1β (IL-1B)T-31C,
tumor necrosis factor α (TNF-α) T-1031C, endothelial constitutive nitric oxide synthase (ecNOS) Glu298Asp, longevity-associated
polymorphism of mitochondrial DNA (mtDNA) 5178 A/C, allergy-associated polymorphism of interleukin-4 (IL-4), and immunity-associated
polymorphism of CD14.
Results A significant association was found between the ALDH2Glu478Lys gene polymorphisms and osteoporosis. In the osteoporosis group
of patients, a significant difference was noted between the Lys/Lys group and the group comprising Glu/Lys and Glu/Glu groups
(namely, the genotypes including Glu alleles). In the Lys/Lys group, after age, sex, BMI, smoking history and alcohol consumption
history had been adjusted for, the morbidity rate was significantly elevated [odds ratio (OR): 3.33; 95% confidence interval
(95% CI): 1.28–8.71; p=0.014], and the effect was even more evident in the sub-group of women with osteoporosis (OR: 4.31; 95% CI: 1.24–14.92; p=0.021).
Conclusions The present results suggest that active prophylactic interventions such as dietary, exercise, and pharmacological therapies
should be offered to non-carriers of the Glu allele (Lys/Lys). 相似文献
4.
Knudsen S Harsløf T Husted LB Carstens M Stenkjaer L Langdahl BL 《Calcified tissue international》2007,80(1):21-30
Interleukin-1α (IL-1α) stimulates bone resorption via osteoclasts. Mononuclear cells from patients with osteoporosis show
increased IL-1α production, and IL-1α mRNA is more often detected in bone biopsies from osteoporotic compared to normal postmenopausal
women. Polymorphisms have been identified in the IL-1α gene; however, none of these has been examined for an effect on bone
phenotypes in Caucasians. We investigated if the polymorphisms in the IL-1α gene affect the risk of osteoporotic fractures,
bone mineral density (BMD), and bone turnover in 462 osteoporotic patients and 336 normal controls. Based on previous studies
of polymorphisms in the gene and data from the International Hap-Map Project, four polymorphisms needed examination in order
to investigate the effect of known polymorphisms in the IL-1α gene. We examined C−1202-T(rs1800794), C–889-T(rs1800587), T155 + 209-C(rs2071373), C155 + 320-T(rs2856838), and G398-T(rs 17561) by Taqman and restriction fragment-length polymorphism assays. BMD was examined by dual-energy X-ray absorptiometry.
Bone turnover was evaluated by serum osteocalcin, serum carboxy-terminal propeptide of human type I procollagen, serum bone-specific
alkaline phosphatase, serum carboxy-terminal telopeptide of type I collagen, and urinary hydroxyproline/creatinine. Genotype
distributions were in Hardy-Weinberg equilibrium. All polymorphisms were in strong linkage disequilibrium. The C allele of the C155 + 320-T polymorphism tended to be more common among patients with vertebral fractures (P = 0.06) and patients with BMD T score <–2.5 (P = 0.05). Furthermore, haplotype 1 was associated with reduced risk of having BMD T score <–2.5 (P = 0.02). None of the other polymorphisms or haplotypes was associated with fracture risk or BMD T score <–2.5. BMD and bone
turnover were not associated with any of the genetic variants. In conclusion, all the polymorphisms within the IL-1α gene
are in strong linkage disequilibrium and not convincingly associated with fracture risk, BMD, or bone turnover. 相似文献
5.
Hoshino S Hosoi T Miyao M Shiraki M Orimo H Ouchi Y Inoue S 《Journal of bone and mineral metabolism》2000,18(3):153-157
A novel variation of the estrogen receptor-α (ERα) gene was identified by polymerase chain reaction–single-strand conformational
polymorphism (PCR-SSCP). It is one base substitution in codon 325 (CCC [allele M] to CCG [allele m]) in exon 4 of the human
ERα gene. This substitution did not cause an amino acid change. We categorized 306 unrelated Japanese postmenopausal women
into three genotypes: MM, Mm, and mm; the frequency of each genotype was 26.5%, 43.1%, and 30.4%, respectively. Then, the
association of this polymorphism with bone mineral density (BMD) of lumbar spine and bone–calcium metabolic markers was studied.
There was no significant difference in BMD of the lumbar spine or most of the bone metabolic markers. However, the urinary
calcium (Ca) excretion ratio (u-Ca/Cre) corrected by creatinine was significantly lower in the genotype mm group compared
with the genotype MM group (MM vs mm, 0.247 ± 0.158 vs 0.200 ± 0.105; P < 0.05). We examined the relationship of restriction fragment length polymorphisms (RFLPs) (PvuII, XbaI) in intron 1 and the polymorphism in exon 4. The frequency of genotype MM was higher in the genotype PPxx, which was reported
to be associated with lower BMD in the same population of Japanese postmenopausal women. The ER polymorphism identified in
this study might be related to some biological mechanisms that regulate calcium metabolism.
Received: Oct. 6, 1997 / Accepted: Sept. 28, 1999 相似文献
6.
Relations between interleukin-1, its receptor antagonist gene polymorphism, and bone mineral density in postmenopausal Korean women 总被引:15,自引:0,他引:15
We investigated the relation between polymorphisms in the interleukin-1(IL-1) and IL-1 receptor antagonist (IL-1ra) gene,
and bone mineral density (BMD) in postmenopausal Korean women. The IL-1α C−889T polymorphism, and IL-1β C−511T polymorphism were examined by restriction fragment length polymorphism, and 86-bp variable number tandem repeat polymorphism
in the IL-1ra gene was analyzed by the polymerase chain reaction and electrophoresis in 202 postmenopausal Korean women. Serum
osteocalcin, and C-telopeptide of type I collagen were measured using a radioimmunoassay and enzyme-linked immunosorbent assay,
respectively. BMD at the lumbar spine and proximal femur was measured by dual-energy X-ray absorptiometer. No significant
differences in BMD or in serum bone markers levels were noted across the IL-1α or IL-1β genotype. There were no significant
differences in the distribution of IL-1α or IL-1β genotype according to the status of bone mass. BMD in women carrying the
A2 allele of the IL-1ra gene was significantly lower than those without this allele, and the A2 allele was more frequent in
osteoporotic women than in normal women. These data suggest that IL-1ra gene VNTR polymorphism is a genetic factor that may
affect BMD in Korean women. 相似文献
7.
CRP Genetic Polymorphism Is Associated with Lymph Node Metastasis in Thoracic Esophageal Squamous Cell Cancer 总被引:1,自引:0,他引:1
Satoru Motoyama MD PhD Masatomo Miura PhD Yudai Hinai PhD Kiyotomi Maruyama MD PhD Shuetsu Usami MD Hajime Saito MD PhD Yoshihiro Minamiya MD PhD Shigeru Satoh MD PhD Katsuyuki Murata MD PhD Toshio Suzuki PhD Jun-ichi Ogawa MD PhD 《Annals of surgical oncology》2009,16(9):2479-2485
Background Lymph node involvement is the most important prognostic factor in thoracic esophageal cancer. A more accurate molecular technique
for diagnosing lymph node metastasis and a better understanding of the molecular mechanisms governing lymph node metastasis
would be highly desirable. The purpose of this study is to examine the association between inflammation-related genetic polymorphisms
and lymph node metastasis.
Methods The study participants were 113 Japanese patients undergoing curative surgery for thoracic esophageal squamous cell cancer.
DNA was extracted from blood samples and genetic polymorphisms in C-reactive protein (CRP), tumor necrosis factor (TNF)-α
and -β, interferon (IFN)-γ, transforming growth factor (TGF)- β, interleukin (IL)-1β, IL-1 receptor antagonist, IL-2, IL-4,
IL-6, IL-6 receptor, IL-10, and IL-12β were investigated using the polymerase chain reaction–restriction fragment length polymorphism
method. We then assessed the association between inflammation-related genes and lymph node metastasis.
Results For CRP 1846C>T polymorphism, the frequency of the 1846T/T genotype was significantly higher in patients with lymph node metastasis
(P = 0.0043), and the odds ratio (3.040) derived from logistic regression models indicated that the 1846T/T genotype significantly
increases the likelihood of lymph node metastasis. In submucosal cancer, the utility of CRP 1846C>T polymorphism for predicting
lymph node involvement was superior to usual methods (computed tomography and ultrasonography), with positive and negative
predictive values of 69% and 75%, respectively.
Conclusions These findings suggest that CRP polymorphism is a potentially effective predictor of lymph node metastasis and may thus be
useful for deciding on treatment strategy. 相似文献
8.
Suzuki M Iizasa T Nakajima T Kubo R Iyoda A Hiroshima K Nakatani Y Fujisawa T 《Annals of surgical oncology》2007,14(9):2636-2642
Background Interleukin-12 receptor β2 (IL-12Rβ2) knock-out mice develop lung adenocarcinoma, and epigenetic silencing by CpG methylation leads to loss of this gene in B-cell
malignancies. The aim of this study was to determine whether IL-12Rβ2 methylation is a common feature in human lung cancer.
Methods We examined mRNA expression of IL-12Rβ2 in lung cancer cell lines, and normal bronchial, and tracheal epithelial cells using RT-PCR, and we examined the methylation
status of IL-12Rβ2 in primary lung cancers.
Results Loss of expression was found in 10 of 13 (77%) NSCLC cell lines, and 2 of 5 (40%) SCLC cell lines compared with normal bronchial
or tracheal cells. Treatment of 11 expression-negative cell lines with a demethylating agent restored expression in all cases.
Aberrant methylation status of IL-12Rβ2 gene was reversely concordant with its mRNA expression. IL-12Rβ2 methylation was detected in 96 of 230 primary NSCLCs (42%) and 3 of 6 primary SCLCs (50%). IL-12Rβ2 methylation correlated with poorer prognosis in lung adenocarcinomas (hazard ratio = 2.33, P = 0.0059).
Conclusions We conclude that epigenetic silencing of IL-12Rβ2 is a frequent event in lung cancers. Aberrant methylation of this gene seems to be a useful predictor of long-term outcome
for adenocarcinoma of the lung. 相似文献
9.
Feng D Ishibashi H Yamamoto S Hosoi T Orimo H Machida T Koshihara Y 《Journal of bone and mineral metabolism》2003,21(4):225-228
Recently, a G/C polymorphism was found at position −573 of the interleukin-6 (IL-6) gene promoter. We investigated how this genetic polymorphism relates to IL-6 production and osteoporosis in elderly Japanese
women. Genomic DNA was extracted from an aliquot of monocytes in the bone marrow; the monocytes were simultaneously used to
form osteoclast-like multinucleated cells (MNCs) and to produce IL-6. Of the 47 subjects with fractures, 96% had a C allele
at position −573 of the IL-6 gene. Only 2 subjects possessed homozygotes of G at that position. We investigated IL-6 levels, MNC formation in bone marrow
culture, and femoral neck bone mineral density (BMD) in the subjects with the GC and CC genotypes. There were no significant
differences between these genotypes as regards IL-6 levels, MNC formation, and femoral neck BMD. However, in the CC genotype,
there was a negative relationship between femoral neck BMD and IL-6 levels, and between femoral neck BMD and MNC formation,
whereas in the GC genotype and combined (GC + CC) genotypes, femoral neck BMD tended to be related to IL-6 levels and MNC
formation. Moreover, the stromal cells in the CC genotype showed higher IL-1α-stimulated IL-6 production than did the stromal
cells in the GC genotype. Our findings suggest that important information might be obtained not only by continued comparison
of different genotypes but also by comparative study within each particular genotype.
Received: April 30, 2002 / Accepted: January 23, 2003
RID="*"
ID="*" Offprint requests to: Y. Koshihara 相似文献
10.
Association of a G2014A Transition in Exon 8 of the Estrogen Receptor-α Gene with Postmenopausal Osteoporosis 总被引:4,自引:0,他引:4
B. Ongphiphadhanakul S. Chanprasertyothin P. Payattikul S. Saetung N. Piaseu L. Chailurkit R. Rajatanavin 《Osteoporosis international》2001,12(12):1015-1019
We report the association of a newly identified synonymous G2014A single nucleotide polymorphism (SNP) which does not alter
the amino acid sequence in exon 8 of the estrogen receptor-α (ERα) gene with osteoporosis in Thai postmenopausal women. Subjects
consisted of 228 postmenopausal women aged more than 55 years divided into two groups – with vertebral or femoral osteoporosis
(n= 106) or without osteoporosis (n= 122) – according to bone mineral density (BMD) criteria. The exon 8 G2014A SNP, which is 6 nucleotides upstream from the
end of the stop codon, was identified by PCR-RFLP. Data are expressed as the mean and 95% CI. The allele frequency of the
G2014A polymorphism was 26.4% in osteoporotic subjects and was significantly higher than that in non-osteoporotic women (15.2%)
(p<0.05). By stepwise logistic regression analysis, it was found that the G2014A polymorphism was related to the presence of
osteoporosis (odds ratio 2.7 per A allele, 95% CI 1.49–4.76) independently of body weight (odds ratio 0.93 per kg, 95% CI
0.89–0.96) and years since menopause (odds ratio 1.12 per year, 95% CI 1.08–1.19). In a multiple linear regression model,
L2–L4 BMD of osteoporotic subjects was associated with body weight (p<0.05), endogenous estradiol levels (p<0.05) and the G2014A genotype (p<0.001), while it was related only to body weight (p<0.05) and estradiol levels in non-osteoporotic women (p<0.05). We conclude that a G2014A SNP in exon 8 of ERα is associated with the presence and severity of postmenopausal osteoporosis.
Linkage disequilibrium between this polymorphism and the 3′-untranslated region of the ERα gene which may participate in the
regulation of ERα gene expression remains to be determined.
Received: 17 October 2000 / Accepted: 11 June 2001 相似文献
11.
Polymorphisms of four bone mineral density candidate genes in Chinese populations and comparison with other populations of different ethnicity 总被引:13,自引:0,他引:13
Lei SF Deng FY Liu XH Huang QR Qin Y Zhou Q Jiang DK Li YM Mo XY Liu MY Chen XD Wu XS Shen H Dvornyk V Zhao L Recker RR Deng HW 《Journal of bone and mineral metabolism》2003,21(1):34-42
Studies on polymorphisms of candidate genes and their association with bone mineral density (BMD) have been reported in many
populations, but few have been reported in Chinese populations. We investigated polymorphisms of the following five commonly
used markers of four prominent BMD candidate genes with the purpose of identifying useful genetic markers for osteoporosis
genetic research in Chinese: the Sp1 and RsaI polymorphisms of the collagen type 1 alpha l (Col1a1) gene, the −174G/C promoter
polymorphism of the interleukin 6 (IL-6) gene, the Asn363Ser polymorphism of the glucocorticoid receptor (GR) gene, and the
T → C polymorphism in intron 5 of the transforming growth factor β1 (TGF-β1) gene. We evaluated these polymorphisms using PCR-RFLP in samples of at least 124 random individuals. We compared the polymorphisms
of these five markers with other populations using the χ2 test and Fisher's exact two-tailed test. For the RsaI polymorphism, only three heterozygotes but no variant homozygote were
identified. For the −174G/C polymorphic site, only one GC heterozygote and no CC homozygote were found. Alleles s, Ser, and A
1
at the Sp1, Asn363Ser, and T → C marker sites that have been found to be polymorphic in other populations were not found
in Chinese. Significant differences of allele and genotype frequency distributions were observed at these polymorphisms (P < 0.001) after comparing with other populations. Our results suggest that variant alleles of the five markers are absent
or too rare to be useful genetic makers in Chinese, despite the fact that they have been commonly used as polymorphic markers
in osteoporosis genetic research in other populations.
Received: April 22, 2002 / Accepted: July 2, 2002
Acknowledgments. The study was partially supported by the Hunan Province Special Professor Start-up Fund (25000612), Chinese National Science
Foundation (CNSF) Outstanding Young Scientist Award (30025025), CNSF Grant (30170504), a grant from Huo Ying-Dong Education
Foundation, and a Seed Fund from the Ministry of Education of P.R. China (25000106). Some investigators (R.R.R., V.D., H.W.D.)
were partially supported by grants from the Health Future Foundation of USA, grants of National Health Institute (K01 AR02170-01,
R01 GM60402-01A1), grants from the State of Nebraska Cancer and Smoking Related Disease Research Program, and U.S. Department
of Energy grant (DE-FG03-00ER63000/A00). We thank all the study subjects for volunteering to participate in the study.
Offprint requests to: H.-W. Deng 相似文献
12.
Rezan Topaloĝlu Ümit Saatçi Meltem Arikan Hande Canpinar Ayşin Bakkaloĝlu Emin Kansu 《Pediatric nephrology (Berlin, Germany)》1994,8(6):649-652
This study was designed to investigate T-lymphocyte subsets interleukin-2 receptor (IL-2R) expression and IL-2 production in minimal change nephrotic syndrome (MCNS). Peripheral blood T-lymphocytes and IL-2R expression were analysed using fluorescein isothiocyanatelabelled CD3, CD4, CD8 and CD25 monoclonal antibodies with flow cytometry. IL-2 production was determined by enzyme immunoassay. Ten children with MCNS in relapse and in remission were evaluated. Thirteen healthy children served as controls. The patients in relapse demonstrated a moderate decrease in the total absolute lymphocyte counts and CD8(+) T-lymphocytes compared with controls (P<0.05) and had a greatly increased IL-2R expression in frashly isolated, unstimulated peripheral lymphocytes compared with patients in remission and controls. While this was not statistically significant, IL-2R expression on cultured lymphocytes stimulated with phytohaemagglutinin was significantly elevated in relapse compared with those in remission and controls (P<0.05). IL-2 production did not correlate well with IL-2R expression and there was no significant difference between the groups. Our results suggest that T-cell subset changes and high IL-2R expression on peripheral lymphocytes may indicate the presence of stimulated T-cell populations in MCNS which could contribute to the immunopathogenesis. 相似文献
13.
Shih-Ching Chang MD PhD Pei-Ching Lin MD Shung-Haur Yang MD PhD Huann-Sheng Wang MD Anna Fen-Yau Li MD PhD Jen-Kou Lin MD PhD 《Annals of surgical oncology》2009,16(8):2323-2330
Background The SDF-1/CXCR4 axis plays an important role in cancer metastasis. SDF1α genetic polymorphisms, including SDF1α-G801A, have been associated with increased cancer risk and may be predictive of distant metastasis. The present study compared
the frequency of 6 SDF1α single-nucleotide polymorphisms (SNPs) in patients with colorectal cancer (CRC) with and without lymph node (LN) metastasis
and determined whether fibroblasts with different SDF-1α genotypes influenced cancer cell proliferation and migration.
Methods The study enrolled 424 patients with primary T3 stage CRC, with and without lymph node metastasis, and a median follow-up
of 48 months. The polymerase chain reaction-sequence specific primers (PCR-SSP) technique was used to identify polymorphisms.
Fibroblasts were harvested from 14 patients with stage II CRC and fibroblast-mediated enhancement of cancer cell proliferation
and migration was evaluated.
Results Only the SDF1α-G801A polymorphism was associated with LN metastasis. The frequency of GA/AA genotypes was significantly higher in patients
with LN metastasis (54.8%) than in patients without LN metastasis (40.7%). In the latter group, disease-free survival was
shorter in patients with the GA/AA genotype (74%) than in patients with the GG genotype (87.6%). In patients with LN metastasis,
disease-free survival was similar regardless of genotype. Expression of SDF-1α mRNA in GA/AA fibroblasts was three times that in GG fibroblasts. GA/AA (but not GG) fibroblasts enhanced colon cancer cell
(HCT116) proliferation and migration. These effects were blocked by an SDF-1α neutralizing antibody.
Conclusions The SDF1α-G801A polymorphism may increase expression of SDF-1α mRNA and be a predictive marker of lymph node metastasis in colorectal cancer. 相似文献
14.
Z. Efstathiadou V. Kranas J. P. A. Ioannidis I. Georgiou A. Tsatsoulis 《Osteoporosis international》2001,12(4):326-331
Several genetic polymorphisms are implicated as determinants of bone mineral density (BMD) in postmenopausal women. These
include the Sp1 polymorphism of the collagen type Iα 1 (COLIA1) gene, the FokI and BsmI polymorphisms of the vitamin D receptor (VDR) gene, and the PvuII and XbaI polymorphisms of the estrogen receptor (ER) gene. The relative importance and the independence of these genetic effects
have not been studied simultaneously in the same population. We evaluated the effects of these polymorphisms on lumbar spine
BMD among 154 postmenopausal Greek women. BMD tended to differ across Sp1 genotypes (mean 0.842 g/cm2 in SS, 0.851 g/cm2 in Ss, 0.763 in ss, age-adjusted p = 0.056), mostly because ss homozygotes had lower BMD (p = 0.018 compared with SS and Ss). No other polymorphisms were associated with BMD in this population (p= 0.53 for FokI, p= 0.94 for BsmI, p = 0.80 for PvuII, p = 0.91 for XbaI). In multivariate modeling, the effect of ss homozygosity was clinically and statistically significant (–0.105 g/cm2, p= 0.013) after adjusting for age, weight, height, hormone replacement use, and the other four polymorphisms. None of the other
four polymorphisms was retained as an independent predictor of BMD in a backward elimination model and no significant synergistic
effects were observed when gene interactions were tested. When all five polymorphisms are considered simultaneously, the Sp1
COLIA1 polymorphism seems to have the most unequivocal effect on BMD, at least in postmenopausal women.
Received: 3 July 2000 / Accepted: 14 November 2000 相似文献
15.
G. Michael Taylor Thomas J. Neuhaus Vanita Shah Susannah Dillon T. Martin Barratt 《Pediatric nephrology (Berlin, Germany)》1997,11(4):404-410
Experimental studies have pointed to charge selectivity as an important determinant of glomerular permeability to macromolecules.
Loss of glomerular basement membrane (GBM) polyanion has been proposed as a cause of the selective proteinuria in minimal
change nephrotic syndrome (MCNS). However, the presence of less-anionic albumin in urine than plasma from MCNS and focal and
segmental glomerulosclerosis (FSGS) patients has been interpreted both as evidence for partial maintenance of charge selectivity
and for involvement of other pathogenic mechanisms. The exact role of charge selectivity in the pathogenesis of nephrotic
proteinuria remains controversial. We have examined the clearance of endogenous proteins of differing size and charge in children
with idiopathic nephrotic syndrome (NS). Chromatofocusing was used to determine the isoelectric points (pIs) of albumins in
paired plasma and urine samples from patients with FSGS (n = 6) and MCNS (n = 6). Charge selectivity was assessed by comparing the pIs of the fractions with the highest albumin concentration (modal
pI) in plasma and urine. The difference between the modal pIs was defined as the delta modal pI. Charge selectivity was also
assessed from the albumin/transferrin and IgG4/IgG1 clearance ratios; size selectivity from the IgG1/albumin and IgG1/transferrin
as well as the IgG4/albumin and IgG4/transferrin clearances. In children with FSGS, the mean (± SD) delta modal pI was – 0.05
± 0.16, and in MCNS – 0.05 ± 0.11. Neither value differed significantly from zero. The albumin/transferrin clearance ratio
showed no significant difference between FSGS and MCNS, but the IgG4/IgG1 clearance ratio was significantly higher in MCNS
(P<0.05). Size selectivity was significantly reduced in FSGS compared with MCNS (for IgG1/transferrin P<0.01 and for IgG1/albumin P<0.05). For IgG4/transferrin and IgG4/albumin, P was <0.05. In conclusion, there was no evidence for residual charge selectivity in idiopathic NS associated with either MCNS
or FSGS during nephrotic-range proteinuria. There was a significant loss of GBM size selectivity in children with FSGS with
heavy proteinuria compared with children with MCNS with heavy proteinuria.
Received August 7, 1996; received in revised form and accepted December 16, 1996 相似文献
16.
Lau HH Ng MY Cheung WM Paterson AD Sham PC Luk KD Chan V Kung AW 《Journal of bone and mineral metabolism》2006,24(3):226-234
Bone mineral density (BMD), an important risk factor for osteoporosis, is a complex trait likely affected by multiple genes.
The linkage and/or association of 13 polymorphic loci of seven candidate genes (estrogen receptor alpha [ERα] and beta [ERβ], calcium-sensing receptor, vitamin D receptor, collagen type 1α1, low-density lipoprotein [LDL] receptor-related protein
5 [LRPS], and transforming growth factor β1) were evaluated in 177 southern Chinese pedigrees of 674 subjects, with each pedigree
identified through a proband having a BMD Z score of −1.28 or less at the hip or spine. A suggestive linkage was detected
between the IVS1-351A/G polymorphism of ERα and spine BMD, and between the 1082G/A, 1730G/A, and D14S1026 polymorphisms of ERβ and BMD at both spine and hip. The quantitative transmission disequilibrium test (QTDT) detected total family association
between 1730G/A of ERβ and BMD at spine and hip; between D14S1026 of ERβ and hip BMD; and between the 266A/G and 2220C/T polymorphisms of LRP5 and hip BMD. Similar total family associations were detected when only the females were analyzed. In addition, the IVS1-397T/C
polymorphism of ERα was associated with spine BMD, and the 266A/G and 2220C/T polymorphisms of LRP5 were associated with femoral neck BMD in the females. A within-family association was detected with the IVS1-397T/C polymorphism
of ERα, and the 266A/G and 2220C/T polymorphisms of LRP5 in the females. The effect of each polymorphism on BMD variance ranged from 1% to 4%. In conclusion, ERα, ERβ and LRP5 are important candidate genes determining BMD variation, especially in females. 相似文献
17.
Wen-Chi Chen Hsi-Chin Wu Huey-Yi Chen Mei-Chen Wu Cheng-Der Hsu Fuu-Jen Tsai 《Urological research》2001,29(5):321-324
Interleukin-1 (IL-1) might play a role in the process of bone loss and hypercalciuria and is therefore considered to be involved in the formation of urinary stones. The aim of this study is to test whether the IL-1beta promoter region, exon 5 region and IL-1 receptor antagonist gene intron 2 polymorphisms could be genetic markers for the susceptibility to the formation of urinary stones. A control group of 152 healthy people and a group of 105 patients with recurrent calcium oxalate stone were examined in this study. Polymerase chain reaction (PCR) analyzed the variable number tandem repeats at intron 2 of the IL-1Ra gene for the polymorphisms. PCR-based restriction analysis was done for the IL-1beta gene polymorphisms of the promoter region and exon 5 by the endonucleases Ava I and Taq I, respectively. The polymorphisms studied in the IL-1beta genes did not reveal a strong association with calcium oxalate stone disease when compared with the control group (promoter region by chi-square test, P=0.627: exon 5 region by Fisher's exact test, P = 0.403). Only two frequent alleles of the IL-1Ra gene corresponding to one and two copies of an 86-bp sequence repeat were identified by PCR. The result revealed significant differences between control individuals and stone patients (P < 0.01. Fisher's exact test). In addition, the frequency of the type I allele in the stone group (99.0%) was higher than in the control group (94.0%). The odds ratio for the type I allele of the IL-1Ra gene in calcium oxalate stone disease is 6.041 (95% CI: 1.683 approximately 21.687). There is an association between urolithiasis and polymorphism in the IL-1Ra gene. No significant difference was found when dividing the stone patients into groups with normocalciuria and hypercalciuria in relation to these genetic polymorphisms. Further studies of the type I allele of the IL-IRa gene are worthwhile because of its correlation with stone disease. In our study, neither the IL-1beta promoter region nor the exon 5 polymorphisms were significantly different when comparing control subjects and calcium oxalate stone patients. 相似文献
18.
Klepstad P Rakvåg TT Kaasa S Holthe M Dale O Borchgrevink PC Baar C Vikan T Krokan HE Skorpen F 《Acta anaesthesiologica Scandinavica》2004,48(10):1232-1239
BACKGROUND: Dispositions for genes encoding opioid receptors may explain some variability in morphine efficacy. Experimental studies show that morphine and morphine-6-glucuronide are less effective in individuals carrying variant alleles caused by the 118 A > G polymorphism in the mu-opioid receptor gene (OPRM1). The purpose of the study was to investigate whether this and other genetic polymorphisms in OPRM1 influence the efficacy of morphine in cancer pain patients. METHODS: We screened 207 cancer pain patients on oral morphine treatment for four frequent OPRM1 gene polymorphisms. The polymorphisms were the -172 G > T polymorphism in the 5'untranslated region of exon 1, the 118 A > G polymorphism in exon 1, and the IVS2 + 31 G > A and IVS2 + 691 G > C polymorphisms, both in intron 2. Ninety-nine patients with adequately controlled pain were included in an analysis comparing morphine doses and serum concentrations of morphine and morphine metabolites in the different genotypes for the OPRM1 polymorphisms. Results: No differences related to the -172 G > T, the IVS2 + 31 G > A and the IVS2 + 691 G > C polymorphisms were observed. Patients homozygous for the variant G allele of the 118 A > G polymorphism (n = 4) needed more morphine to achieve pain control, compared to heterozygous (n = 17) and homozygous wild-type (n = 78) individuals. This difference was not explained by other factors such as duration of morphine treatment, performance status, time since diagnosis, time until death, or adverse symptoms. CONCLUSION: Patients homozygous for the 118 G allele of the mu-opioid receptor need higher morphine doses to achieve pain control. Thus, genetic variation at the gene encoding the mu-opioid receptor contributes to variability in patients' responses to morphine. 相似文献
19.
20.
Host Cytokine Genotype is Related to Adverse Prognosis and Systemic Inflammation in Gastro-Oesophageal Cancer 总被引:8,自引:0,他引:8
Deans C Rose-Zerilli M Wigmore S Ross J Howell M Jackson A Grimble R Fearon K 《Annals of surgical oncology》2007,14(2):329-339
Background Systemic inflammation has been linked with reduced survival in cancer, however, the role of the host cytokine genotype versus
tumour phenotype in the generation of this response is not clearly established. This study examined the relationship between
cytokine polymorphisms (IL-1β 511, IL-6 174, IL-10 1082, TNFα 308 and LTα +252) and serum cytokine concentrations, serum CRP
concentration and survival duration in patients with gastro-oesophageal malignancy.
Methods Two hundred and three newly diagnosed patients with gastric or oesophageal cancer had serum CRP and cytokine concentrations
determined by ELISA. SNP genotyping was performed by Taqman allelic discrimination genotyping and compared with the genotype
observed in 266 healthy volunteers. Clinico-pathological information was collected prospectively and survival duration was
recorded.
Results Distribution of the cytokine genotypes was similar between patients and controls. The IL-6 174 CC and IL-10 1082 GG genotypes
were associated with elevated serum CRP (P = .03, P = .01, respectively; Mann–Whitney U test) and sTNF-R (P = .015, P = .02) concentrations. These genotypes were also associated with reduced survival duration (P = .01, P = .047; log-rank test). TNFα AA genotype was also associated with reduced survival duration on univariate (P = .032) and multivariate analysis (P = .006, multivariate model), but not with inflammatory markers. No other cytokine polymorphisms were associated with systemic
inflammatory markers or prognosis.
Conclusions There is a pro-inflammatory cytokine haplotype (IL-6 CC, IL-10 GG, TNFα AA) that is associated with adverse prognosis that
may act, at least in part, through an inflammatory mediated mechanism. Determining patients’ cytokine haplotype may improve
prognostication and allow stratification for intervention studies. 相似文献