Association between respiratory function and osteoporosis in pre- and postmenopausal women

OBJECTIVE: To investigate the relationships between respiratory function and osteoporosis, 132 premenopausal and 98 postmenopausal women were evaluated. METHODS: Bone mineral density (BMD) was measured with dual-energy X-ray absorptiometry. Pulmonary function and anthropometric parameters were measured using a spirometer and a body composition analyzer. RESULTS: Lumbar spine and proximal femur BMDs in postmenopausal women with forced expiratory volume in 1s (FEV1) > or = 92.0% averaged 0.83 +/- 0.12 g/cm2 and 0.67 +/- 0.11 g/cm2, which were significantly above the values (0.76 +/- 0.14 g/cm2 and 0.61 +/- 0.12 g/cm2, P < 0.05) in those with FEV1 <92.0%. The prevalences of osteoporosis at lumbar spine and proximal femur were 59.2 and 46.9% in the postmenopausal women with peak expiratory flow rate (PEFR) <5.12 l/s, significantly higher than those of osteoporosis at the corresponding sites in the women with > or = 5.12 l/s (36.7 and 20.4%, P < 0.05). Lumbar spine and proximal femur BMDs were positively correlated with FEV1 (r = 0.28, P < 0.05; r = 0.31, P < 0.05) and PEFR (r = 0.35, P < 0.05; r = 0.23, P < 0.05) in postmenopausal women; however, no significant correlations were observed in premenopausal women. CONCLUSION: Pulmonary function seems to be more closely associated with BMD in postmenopausal women than in premenopausal women. Poor respiratory function may be an indicator of postmenopausal women at increased risk of osteoporosis.     

Association between polymorphisms of TP53 and MDM2 and prostate cancer risk in southern Chinese

Alterations in the TP53 and MDM2 genes appear to be important in the development of many human tumors, but evidence is conflicting on associations between polymorphisms in these genes and risk of prostate cancer (PCa). The influence of TP53 codon 72, MDM2 SNP309, and MDM2 C1797G polymorphisms in southern Chinese PCa patients was investigated. In the comparison of genotype distributions of TP53 codon 72 between cases and controls, the adjusted odds ratios for PCa associated with the Pro/Pro, Arg/Pro, and Arg/Arg genotypes were 1.00, 1.89 (95% CI = 1.20-2.97), and 2.01 (95% CI = 1.11-3.64), respectively; however, MDM2 SNP309 and C1797G did not show any significant difference between cases and controls. When TP53 and MDM2 polymorphisms were combined based on the numbers of variant risk alleles (i.e., G-allele of TP53 codon 72, G-allele of MDM2 SNP309, and G-allele of MDM2 C1797G), individuals with 3-5 variants had a 1.56-fold greater risk of PCa than those with 0-2 variants (95% CI = 1.07-2.26). Moreover, subjects with 0-2 variants had 33.3% positive p53 expression, whereas subjects with 3-5 variants had 23.3% p53 expression (P = 0.39). These findings suggest that TP53 and MDM2 polymorphisms play a role in PCa susceptibility in southern Chinese Han population.     

A meta-analysis about the association between −1082G/A and −819C/T polymorphisms of IL-10 gene and risk of type 2 diabetes

The present meta-analysis was conducted to investigate the association between the −1082G/A and −819C/T polymorphisms of the IL-10 gene and risk of type 2 diabetes mellitus (T2DM). Relevant articles were identified by searching PubMed, Embase, and Web of Science. Pooled odds ratios (ORs) were used to assess the strength of the association between target polymorphisms and the risk of T2DM. Significant associations between the −1082G/A polymorphism and T2DM were found for the allele contrast (OR = 0.90, 95% CI: [0.83, 0.98], P = 0.02), homozygote contrast (OR = 0.82, 95% CI: [0.69, 0.97], P = 0.02), and recessive genetic model (OR = 0.85, 95% CI: [0.74, 0.96], P = 0.01). However, no significant association was found for the dominant genetic model (OR = 0.91, 95% CI: [0.80, 1.05], P = 0.08). The association between −819C/T polymorphism and T2DM was significant for the allele contrast (OR = 0.73, 95% CI: [0.64, 0.84], P < 0.01); however, no significant associations were found for −819C/T in the homozygote contrast (OR = 1.01, 95% CI: [0.38, 2.67], P = 0.99), dominant genetic model (OR = 0.94, 95% CI: [0.50, 1.77], P = 0.86), and recessive genetic model (OR = 0.92, 95% CI: [0.50, 1.68], P = 0.78). No significant publication bias was detected. This meta-analysis suggests that allele A of −1082G/A and allele C of −819C/T in the IL-10 gene have potentially protective effects in terms of risk of T2DM.     

Association between STAT5 polymorphisms and glioblastoma risk in Han Chinese population

The aim of this study was to investigate the associations between STAT5 gene polymorphisms and glioblastoma (GBM) risk predisposition. We undertook a case–control study to analyze two STAT5 polymorphisms (STAT5a rs11079041 and STAT5b rs2293157) in a Han Chinese population, by extraction of genomic DNA from the peripheral blood of 328 patients with glioma and 342 control participants, and performed STAT5 genotyping using DNA sequencing. The obtained results indicated that overall, no statistically significant association was observed in STAT5a rs11079041. Nevertheless, STAT5b rs2293157 G/T genotype was at increased risk of glioma (P = 0.001). Furthermore, rs2293157T allele was more significantly prognostic in patients suffering from glioblastoma compared to other subtypes of gliomas (P < 0.001; odds ratio (OR) = 5.14, CI 95%: 2.70–9.79). These findings led us to conclude that polymorphism in STAT5b rs2293157 G/T was observed to be associated with susceptibility of glioblastoma. Nevertheless, further investigation with a later confirmation in another ethnical or geographical cohort is required.     

Association analysis between polymorphisms in the dopamine D2 receptor (DRD2) and dopamine transporter (DAT1) genes with cocaine dependence

Genetic research on cocaine dependence (CD) may help clarify our understanding of the disorder as well as provide novel insights for effective treatment. Since dopamine neurotransmission has been shown to be involved in drug reward, related genes are plausible candidates for susceptibility to CD. The dopamine receptor D₂ (DRD2) protein and dopamine transporter (DAT1) protein play regulatory roles in dopamine neurotransmission. The TaqI A single-nucleotide polymorphism (SNP) in the DRD2 gene and the 3′ variable number tandem repeat (VNTR) polymorphism in the DAT1 gene have been implicated in psychiatric disorders and drug addictions. In this study, we hypothesize that these polymorphisms contribute to increased risk for CD. Cocaine-dependent individuals (n = 347) and unaffected controls (n = 257) of African descent were genotyped for the polymorphisms in the DRD2 and DAT1 genes. We observed no statistically significant differences or trends in allele or genotype frequencies between cases and controls for either of the tested polymorphisms. Our study suggests that there is no association between the DRD2 and DAT1 polymorphisms and CD. However, additional studies using larger sample sizes and clinically homogenous populations are necessary before confidently excluding these variants as contributing genetic risk factors for CD.     

骨代谢相关基因多态性与盐酸雷洛昔芬对绝经后骨质疏松妇女骨密度和骨转换指标影响的关系

目的了解骨代谢相关基因多态性与盐酸雷洛昔芬( raloxifene,RLX)对绝经后骨质疏松妇女骨密度(bone mineral density, BMD)和骨转换指标影响的关系.方法为随机、对照和双盲试验,入选47～74岁68例无亲缘关系的绝经后骨质疏松汉族妇女,随机分为RLX组和安慰剂组(各34例),RLX组日服RLX 60 mg,安慰剂组服与RLX外观一致的安慰剂,共1年.在服药前、服药后6月和12月时,检测BMD和骨转换指标包括血清1型胶原羧基末端肽(C-telopeptide, CTX)和骨钙素(osteocalcin, BGP).分析雌激素受体1基因(estrogen receptor 1 gene,ESR1)Xba Ⅰ和PvuⅡ位点、ESR2基因RasⅠ位点、维生素D受体基因(vitamin D receptor, VDR)FokⅠ和CDX2结合位点的多态性. 结果共58例完成整个试验,研究结束时RLX组腰椎2～4(L2～4)、全髋部和大转子BMD增加的百分数,以及血清CTX和BGP水平下降的百分数与安慰剂组比较差异均有统计学意义(P<0.05或P<0.01).治疗后12个月,RLX组VDR FokⅠ FF基因型者(n=8)全髋部和大转子BMD值平均下降各为1.98%±4.86%和2.26%±4.73%,而Ff/ff基因型者(n=21)平均增加各为2.52%±2.75%和2.74%±2.97%(P<0.05);ESR1 PvuⅡ位点PP/Pp基因型者(n=17)全髋部BMD明显增加(2.12%±2.78%),而pp基因型者(n=12)呈下降(-1.34%±3.73%)(P<0.05).但上述5个位点多态性与安慰剂组各指标变化均无相关性. 结论 RLX对绝经后骨质疏松妇女BMD的作用受VDR基因FokⅠ和ESR1基因PvuⅡ多态性的调节.在临床选择该药物时,可根据应用对象的基因型做有益决策之用.     

Association of estrogen receptor alpha gene polymorphisms and lifestyle factors with calcaneal quantitative ultrasound and osteoporosis in postmenopausal Vietnamese women

Abtract Genetic and lifestyle factors are important in the pathogenesis of osteoporosis. We investigated the relationships of PvuII and XbaI polymorphisms of the estrogen receptor alpha (ER-α) gene, lifestyle factors with speed of sound at the calcaneus (calcaneal SOS) and osteoporosis in a population-based study of 140 healthy postmenopausal women. By an analysis of covariates, women with higher copies of P or X alleles had higher calcaneal SOS compared with others (P=0.012, PP vs. pp; P=0.045, Xx vs. xx). Women with lower copies of px or higher copies of PX haplotypes had higher calcaneal SOS compared with others (P=0.021, 0 px vs. 2 px; P=0.011, 1 PX vs. 0 PX). The px and PX haplotypes, age and years since menopause were found to be independent predictors of calcaneal SOS in multiple linear regression models. Using logistic regression, we found an increased osteoporosis risk with evidence for a px haplotype dose effect (OR=2.82, 95% CI=1.50–5.31, P=0.001) and for a PX haplotype dose effect (OR=0.42, 95% CI=0.19−0.93, P=0.033). An increased educational level was associated with a reduced risk of osteoporosis (P=0.035 in the model with px, P=0.044 in the model with PX). In conclusion, the present study suggests that PvuII and XbaI polymorphims of the ER-α gene, age, years since menopause and educational level are associated with bone density, as assessed by calcaneal SOS, and osteoporosis in postmenopausal Vietnamese women.     

Associations between ABO blood groups and osteoporosis in postmenopausal women

To investigate whether any significant differences exist in the prevalence of osteoporosis in relation to ABO blood groups, 227 postmenopausal women were evaluated for bone mineral density (BMD), body composition, and anthropometric variables. There were no significant differences in age, anthropometric parameters, or body composition between women with O blood type and those with non-O blood types. However, lumbar spine and proximal femur BMDs in subjects with blood type O averaged 0.87+/-0.13 g/cm2 and 0.76+/-0.12 g/cm2, respectively, which were significantly above the values in those with non-O blood types (0.72+/-0.11 g/cm2 and 0.61+/-0.09 g/cm2, p<0.05, respectively). Among the ABO blood groups, the women with blood type AB showed the lowest BMDs (0.71+/-0.10 g/cm2 and 0.59+/-0.09 g/cm2) in the lumbar spine and proximal femur. The prevalences of osteoporosis in the proximal femur and lumbar spine averaged 2.3- and 1.7-fold higher in women with blood type AB than in those with blood type O. Thus, ABO blood group status seems to have a significant relationship to the prevalence of osteoporosis in postmenopausal women.     

Relationship between plasminogen activator inhibitor type-1 (PAI-1) gene polymorphisms and osteoporosis in Turkish women

OBJECTIVE:

The development of osteoporosis is associated with several risk factors, such as genetic structures that affect bone turnover and bone mass. The impact of genetic structures on osteoporosis is not known. Plasminogen activator inhibitor type-1 regulates the bone matrix and bone balance. This study assessed the correlation between plasminogen activator inhibitor type-1 gene 4G/5G polymorphisms and osteoporosis in a population of Turkish women.

METHODS:

A total of 195 postmenopausal female patients who were diagnosed with osteoporosis (Group I) based on bone mineral density measurements via dual-energy x-ray absorptiometry and 90 females with no osteoporosis (Group II) were included in this study. Correlations between PAI-1 gene 4G/5G polymorphisms and osteoporosis were investigated through the identification of PAI-1 gene 4G/5G polymorphism genotypes using the polymerase chain reaction.

RESULTS:

No significant differences in the genotype and allele frequency of 4G/5G plasminogen activator inhibitor type-1 polymorphisms were observed between the two groups, and both groups exhibited the most frequently observed 4G5G genotype.

CONCLUSION:

No correlation between the development of osteoporosis in the female Turkish population and 4G/5G plasminogen activator inhibitor type-1 gene polymorphisms was observed.     

Association between two single nucleotide polymorphisms of PDCD6 gene and increased endometriosis risk

Programmed cell death 6 (PDCD6), a calcium binding protein of the penta EF-hand protein family, and its receptors are involved in regulation of apoptosis pathways. To evaluate the relationship between genetic polymorphisms of PDCD6 gene and endometriosis (ED) risk, we investigated the association of two single nucleotide polymorphisms (SNPs) of PDCD6 gene (rs4957014 and rs3756712) in 220 endometriosis patients and 386 unrelated healthy controls. The genotypes of these two SNPs were determined by using polymerase chain reaction (PCR)–restriction fragment length polymorphism (RFLP) and DNA sequencing methods. Significantly increased endometriosis risk was observed to be associated with G allele of rs4957014 locus (OR = 1.31, 95% CI = 1.03–1.69). We have also observed increased ED risk was statistically associated with rs4957014 polymorphism in a dominant model (OR = 1.52, 95% CI = 1.09–2.13). Although no association has been found between ED risk and the allele frequencies of rs3756712 locus (a marginal P = 0.066, OR = 1.27, 95% CI = 0.98–1.65), but in a dominant model, increased endometriosis risk was significantly associated with rs3756712 polymorphism (OR = 1.54, 95% CI = 1.11–2.17). In conclusion, the current study indicates that PDCD6 gene may be a new susceptibility gene to endometriosis.     

Association of the osteoprotegerin gene polymorphisms with bone mineral density in postmenopausal women

OBJECTIVES: Osteoprotegerin (OPG) is a recently discovered member of the tumour necrosis factor receptor superfamily. It plays a crucial role in the control of bone resorption and its gene could therefore be a good candidate gene for osteoporosis. The aim of our work was to find polymorphisms in the OPG gene and to investigate their possible contribution to the genetic susceptibility to osteoporosis by testing for their association with bone mineral density (BMD). METHODS: The whole OPG gene coding region was screened for the presence of polymorphisms in a group of 60 osteoporotic women by single-strand conformation polymorphism analysis (SSCP) approach. Association of the discovered polymorphisms with bone mineral density was investigated in 136 Slovenian postmenopausal women. RESULTS: We detected eight OPG gene polymorphisms that were confirmed by direct DNA sequencing, deletion 4752_4753delCT and nucleotide substitutions 1181G>C, 1217C>T, 1284G>A, 4501C>T, 6893A>G, 6950A>C and 8738T>A. Nucleotide substitutions 1284G>A and 8738T>A have not been previously described. Polymorphisms 4752_4753delCT, 6893A>G and 6950A>C were in complete linkage and the same was true for 1217C>T and 4501C>T. The association with BMD was found only for polymorphism 1181G>C. Subjects with genotype 1181GG had significantly lower lumbar spine BMD than subjects displaying 1181GC. CONCLUSIONS: By our approach we detected eight polymorphisms in the OPG gene. According to our analysis polymorphism 1181G>C is associated with BMD and could therefore be considered as an element of genetic susceptibility to osteoporosis.     

Association of TLR4 and TLR5 gene polymorphisms with Graves’ disease in Chinese Cantonese population

Graves’ disease (GD) is postulated to be caused by the combined effects of susceptibility genes and environmental triggers. Toll like receptors (TLRs) play a role in the activation of innate and adaptive immune responses in mammalians. The aim of this study was to evaluate the potential association of TLR4 and TLR5 gene polymorphisms with GD in Chinese Cantonese population. Four single nucleotide polymorphisms (SNPs), rs11536889 and rs7873784 in TLR4, rs2072493 and rs5744174 in TLR5, were evaluated in 332 GD patients and 351 unrelated controls from Chinese Cantonese population. The minor allele C of TLR5 rs5744174 decreased the risk to GD in females (OR_{C vs. T} = 0.63; p = 0.003; p_trend = 0.003). Under a dominant model, rs5744174 conferred a protective effect in all cases (OR_{CC/CT vs. TT} = 0.65; p = 0.009) or female subset (OR_{CC/CT vs. TT} = 0.57; p = 0.002). Under a co-dominant model, rs5744174 also conferred a protective effect in all cases (OR_{TC vs. TT} = 0.64; p = 0.008) and females (OR_{TC vs. TT} = 0.57; p = 0.002). The haplotype A-C of TLR5 (rs2072493–rs5744174) decreased the risk of GD in females (OR = 0.62; p = 0.002). The other three SNPs were not found associated with GD. This study provided evidence that polymorphisms in TLR5 might be associated with decreased susceptibility of GD in females.     

Association between C-reactive protein and pulmonary function in postmenopausal women

Objectives

The objective of this study is to investigate the association of CRP and impaired pulmonary function in postmenopausal women.

Methods

The study was carried out in Gangnam Severance Hospital in Korea between March 2006 and October 2008. A total of 5978 healthy women subjects (age range, 20–75 years) were recruited from Seoul. We performed a cross-sectional study to evaluate the association of CRP with impaired pulmonary function, especially the restrictive pattern in 1555 nonsmoking postmenopausal women. We evaluated CRP as a categorical variable and constructed three groups (a very low risk group, CRP < 0.5 mg/dl; a low risk group, 0.5–1.0 mg/dl; a medium and high risk group, 1.0–10.0 mg/dl). The odds ratios (ORs) for a low FVC were calculated across all three groups.

Results

CRP levels are negatively associated with forced expiratory volume (FEV₁)/forced vital capacity (FVC) and FVC after adjustment for confounding variables. The adjusted ORs (95% CIs) for a low FVC according to three groups were 1.00 (reference), 2.08 (1.03–4.20), and 2.55 (1.31–4.98) in postmenopausal women after adjusting for confounding variables.

Conclusions

In summary, increased C-reactive protein (CRP) levels are strongly and independently associated with impaired pulmonary function and more frequent a low FVC in postmenopausal women.     

Relationship between blood pressure levels and bone mineral density in postmenopausal Turkish women

Introduction

We investigated the association between bone mineral density (BMD) detected by dual-energy X-ray absorptiometric (DXA) method and blood pressure (BP) in a large sample of postmenopausal women.

Material and methods

The current study was based on a retrospective analysis of 586 postmenopausal women with a mean age of 60.8 ±8.8 years, who were screened for osteopenia or osteoporosis by DXA. Patients with hypertension (HT, n= 306) were compared with normotensive (NT, n = 290) individuals. Bone mineral density results for the femur neck and spine were classified into 3 groups according to World Health Organization criteria: normal (T score > –1.0 SD), osteopenia (T score –1.0 to –2.5 SD) and osteoporosis (T score < –2.5 SD). Patients with osteopenia or osteoporosis (T score < –1.0 SD) were grouped as having low bone mass (LBM).

Results

There were no significant differences in femur T score, femur BMD, femur Z score, spinal T score, spinal BMD and spinal Z score between hypertensive and normotensive groups. The group of patients with low bone mass calculated from femur T scores had higher age, systolic BP, duration of hypertension and duration of menopause, but lower BMI. Similarly, patients with low spine BMD had higher age and duration of menopause, but lower BMI. Linear regression analysis showed a significant correlation between systolic BP and femur BMD and T score values. Furthermore, logistic regression analysis revealed that hypertension is an independent predictor of spinal osteopenia and osteoporosis.

Conclusions

The presence of hypertension is an independent predictor of spinal low bone density in Turkish women after menopause.     

Association of KIT gene polymorphisms with bone mineral density in postmenopausal Korean women

Bone mineral density (BMD) is a major factor for determining bone strength and osteoporotic fracture risk, and is determined by environmental and multiple genetic factors. KIT, which encodes a transmembrane receptor with tyrosine kinase activity, plays an important role in the differentiation of osteoclasts. We examined the associations between KIT gene polymorphisms and BMD in postmenopausal Korean women. All exons, their boundaries, and the promoter region (approximately 1.5 kb) from 24 individuals were directly sequenced. Eighteen polymorphisms were identified, and three single-nucleotide polymorphisms (SNPs) were genotyped in all study participants (n = 946). BMD at the lumbar spine and femoral neck was measured using dual-energy X-ray absorptiometry. The mean age of the study subjects was 58.9 ± 7.5 years, and the mean number of years since menopause was 9.6 ± 7.9 years. None of the three SNPs (−1694G>T, +41894A>G, and +49512G>A) was significantly associated with BMD value. However, multivariate analysis showed that the ht3 (−1694T-+41894A-+49512G) was significantly associated with lower BMD at the femoral neck (P = 0.007 in the recessive model). These findings indicate that KIT-ht3 may be a useful genetic marker for osteoporosis and that KIT may have a role on bone metabolism in humans. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. S.-Y. Kim and J.-Y. Lee are co-first authors.