Impact of genetic variation of tumor necrosis factor-α on gestational hypertension

Background The mechanisms responsible for the pathogeneses of gestational hypertension and preeclampsia are unclear. Tumor necrosis factor-1α （TNF-1α） is a pro-inflammatory Th1-type cytokine. TNFA gene is located in the human leukocyte antigen （HLA） class Ⅲ region of the major histocompatibility complex （MHC） on chromosome 6. The high TNF-1α mRNA expression may be associated with the TNF2 （A） allele, which is the polymorphism of TNF-1α at position - 308 in promoter region. This study assessed whether the TNF2 （A） allele at position -308 plays a role in the alteration of blood pressure （BP） and urinary protein excretion during pregnancy. Methods The original prospective cohort study comprised 1623 pregnant women from January 2000 to October 2001. The G/A polymorphism was done by restriction fragment length polymorphism （RFLP） analysis with Nco I enzyme. Results The distributions of the G/A polymorphism of TNF-1α in the promoter region at position -308 were wild-type 72.4% and variant 27.6%, respectively. The frequency of TNF2 （A） allele was approximately 0.15 for Caucasian pregnant women in the study. It was not significantly different in the distributions of genotypes and G/A allele frequencies among the three groups of pregnant women with gestational hypertension, preexisting hypertension and normal blood pressure （P〉0.05）. The maternal blood pressure in the third trimester was significantly higher in the group of women possessing the TNF2 （A） allele compared to homozygous for the TNF1 （G） allele （systolic BE P〈0.01 and diastolic BE P〈0.05）. The elevated blood pressure in the TNF2 （A） group was accompanied by higher urinary protein excretion in the third trimester （P〈0.05）. The blood pressure and urinary protein excretion did not change apparently between the two groups in the first and second trimesters （P〉0.05）. Conclusions Maternal TNF2 （A） allele of TNF-1α promoter region at position -308 could play a role in the alteration of blood pressures and/or enhancement of urinary protein excretion during pregnancy, and might play an important role in the development of both gestational hypertension and preeclampsia.     

The investigation for the relationship among serum leptin, erythrocyte membrane Ca^2＋-ATPase activity and hypertensive disorder complicating pregnancy

Objective: To study the significance of Leptin and the activity of erythrocyte membrane Ca2 -ATPase (EMCA) in the development of hypertensive disorder complicating pregnancy. Methods: Radioimmunoassay was used to test the level of serum Leptin,and the activity of EMCA was determined chemically in 38 pregnant women with hypertensive disorder complicating pregnancy and 36 normotensive pregnant women. Results: The level of serum Leptin in hypertensive disorder complicating pregnancy(gestational hypertension: 13.76 ± 3.46 ng/ml; preeclampsia:15.76 ± 5.47 ng/ml; eclampsia: 18.32 ± 6.38 ng/ml)was significantly higher than that in normotensive pregnant women (11.33 ± 2.93 ng/ml), respectively. The average EMCA activity of patients with hypertensive disorder complicating pregnancy (gestational hypertension: 1.65 ± 0.24 μmol· pi/mg·h; preeclampsia: 1.37 ± 0.19 μmol·pi/mg·h; eclampsia:1.12 ± 0.14 μ mol·pi/mg·h) was significantly lower than that of normotensive pregnant women(1.83 ±0.38 μ mol·pi/mg·h),respectively. There was a negative correlation between the level of serum Leptin and the activity of RMCA in hypertensive disorder complicating pregnancy (r = -0.63). Conclusion: Inhibition of EMCA activity of erythrocyte in hypertensive disorder complicating pregnancy may increase cytoplasmic free calcium, which contributes to the development of hypertensive disorder complicating pregnancy. The negative correlation between the level of serum Leptin and the activity of EMCA, also suggested that serum Leptin and the activity of EMCA may play a role in the development of hypertensive disorder complicating pregnancy.     

Association of RFC-1 80A→G and MTHFR 677C→T polymorphisms with neural tube defects in Ukrainian population

【Objective】To evaluate the roles of 80A→G polymorphism of RFC-1 gene encoding the reduced folate carrier protein and 677C→T polymorphism of 5,10-methylenetetrahydrofolate reductase gene(MTHFR)in neural tube defects(NTD)risk in Ukrainian population.【Methods】The folate status,homocysteine levels and genotypes were assessed in 42 mothers of fetuses with spina bifida,anencephaly and encephalocele with the age of 19-40 years.Serum folate and plasma homocysteine levels were estimated using chemiluminescence technology.DNA was isolated from peripheral leukocytes obtained from blood using standard procedures.The presence of the RFC-1 80A→G polymorphism was investigated using polymerase chain reaction(PCR).Real time PCR was used to detect the presence of the 677C→T mutation in the MTHFR gene.【Results】Genotype frequencies for RFC-1 80A→G in NTD group were:homozygous wild type in 9(21.4%),heterozygous type in16(38.1%)women;17(40.5%)women surveyed were found homozygous for the mutant allele genotype of RFC-1(GG).Homozygous for the indicated mutation was found in 57.1%of women with fetal anencephaly in the past history and 29.6%of women with spina bifida fetuses.Allelic frequency in this group of women for allele A was 40.5%(34),for allele G was 59.5%(50).Among women with 80A/A genotype of RFC-1 gene reduced levels of serum folic acid were noticed only in 6(35.5%),but hyperhomocysteinemia was found in 10(58.8%)women.【Conclusion】80G→A polymorphism of RFC-1 gene is a potential genetic factor in the formation of fetus NTD in women of South Ukraine.     

Relationship between polymorphism of cystathionine beta synthase gene and congenital heart disease in Chinese nuclear families

Objective To study the relationship between polymorphism of cystathionine beta synthase （CBS） gene and development of congenital heart disease （CHD）. Methods One hundred and twenty-seven CHD case-parent triads were recruited from Liaoning Province as patient group, and 129 healthy subjects without family history of birth defect were simultaneously recruited as control group together with their biological parents. For all subjects the polymorphism of CBS gene G919A locus was examined by PCR-ARMS method, Results The frequencies of three genotypes （w/w, w/m, and m/m） in control group were 27.2%, 58,4%, and 14.4%, respectively, with no significant difference in gender. A significant difference in the allele frequency was found between CHD patients and controls, the wild allele frequency was 67,9% in patients and 55.7% in controls CHD parents＇ genotype distribution was significantly different from that in controls. Further comparison of each type of CHD showed that genotype frequencies in several CHD subtypes were significantly different from those in their corresponding controls. The results of TDT analysis showed that no allele transmission disequilibrium existed in CHD nuclear families. Conclusions CBS gene G919A mutation is associated with the development of CHD, and the mutated allele may decrease the risk of CHD.     

POLYMORPHISM OF ANGIOTENSIN I TYPE 1 RECEPTOR GENE IN ELDERLY PATIENTS WITH ESSENTIAL HYPERTENSION

Objective To detect the A/C1165 polymorphism of angiotensin Ⅱ type Ⅰ receptor (AT1-R)gene in essential hypertensive elderly. Methods The A/C1166 polymorphism of AT1-R gene was assessed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in a case-control study of 87 essential hypertensive elders (EH) and 55 normolensive elders (NT). Results The genotype frequencies of AA, AC, CC were 0 .805 , 0.161, 0 .034 in EH group and 0 .927 ,0 .073 ,0 .000 in NT group respectively. The frequency of C61166 allele was higher in EH group (0.115) than in NT group (0 .036 )(P<0 .05 ). Conclusion The resultsindicate that A/C1166 polymorphism of AT1-R gene may be associated with essential hypertension in elderly.     

Association of gene polymorphisms of tumour necrosis factor-α and interleukin-13 with chronic obstructive pulmonary disease in Han nationality in Beijing

Background Genetic factors are believed to play a role in the individual susceptibility to chronic obstructive pulmonary disease (COPD). A single nucleotide polymorphism (SNP) of tumour necrosis factor-α (TNF-α)has been reported but inconsistent results may arise from different populations and phenotypes of COPD. There are only a few published studies of interleukin-13 (IL-13) SNPs on COPD. The SNPs of TNF-α and IL-13 have not been studied in the Chinese population. This research was conducted to study the frequencies of IL-13 gene promoter 1055 (IL-13-1055) and TNF-α gene-308 polymorphisms in the patients with COPD and to investigate the effect of those genetic polymorphisms on COPD in the Chinese population.Methods A cohort of COPD patients and age matched controls were recruited from an inpatient hospital service in Beijing. Venous blood was obtained and genomic DNA was extracted from peripheral blood monocytes using standard method. Genomic DNA was used as a template for amplification by polymerase chain reaction(PCR) to determine the polymorphism at -1055 in the length polymorphism (RFLP) was used to determine polymorphisms in the TNF-α gene-308 position. The products were investigated by sequence analysis also.Results One hundred and eleven COPD patients and 97 controls were studied. Seventy-five cases were current smokers in COPD patients and 36 were current smokers in controls. The frequencies of TT genotype in the IL-13 gene promoter region were 11.7% ( 13/111 ) in the COPD group and 13.4% (13/97) in the controls (P =0. 713). However, the OR value of TT genotype was significantly increased to 6.4 (95% CI 1.62 -25.39) in the smokers with COPD. TT genotype was also positively related to family history of COPD, OR =7. 7 (95% CI 1.37 -43.80). The frequencies of A allele in the TNF-α gene were 5.9% in COPD and 3. 1% in controls (P=0. 131 ). The OR value of A allele was 5.0 (95% CI 1.011 to 25. 059) in smokers with COPD.Conclusions There is no significant difference in the frequencies of the TT genotype of IL-13-1055 or the A allele of the TNF-α between Han Chinese patients with COPD versus control. Thus, it does not appear that these SNPs are independent factors in COPD for Han nationality in Beijing. However, these SNPs may increase the risk of COPD among smokers.     

Polymorphism of the leptin gene promoter in pedigrees of type 2 diabetes mellitus in Chongqing, China

Background It has been shown that the presence of leptin is associated with deabefes, glucose wefabolism and insulin metablism. In this research, we evaluated the presence of the leptin C^-2549→A polymorphism in the Chinese population in Chongqing and verified its association with plasma leptin levels and anthropometric, metabolic, and clinical parameters.Methods Two hundred and sixty-nine patients with diabetes, 135 non-diabetic first-degree relatives of the patients, and 85 healthy controls were screened for the presence of C^-2549→A polymorphism using a PCR-RFLP assay. Body mass index, fasting leptin, fasting insulin, fasting glucose and homeostatic model assessment for insulin resistance ( HOMA)-IR were also determined.Results In the type 2 diabetes group, AA genotype frequency (6.32%) and A allele frequency(34.94%) was higher than in normal controls (1.18% and 25.29%, respectively). Diabetic patients with the AA genotype had lower fasting leptin and insulin levels than those with other genotypes.Carriers with the AC genotype had decreased fasting leptin and insulin levels and longer duration of disease as compared with those with CC genotype. The HOMA-IR of patients with AA or AC genotypes was lower than those with the CC genotype. In non-diabetic relatives group, individuals with the AA genotype had a lower fasting leptin level than those with the AC genotype. The fasting insulin and HOMA-IR level of carriers of the AA or AC genotype were lower than those of the CC genotype.Conclusion The C^-2549→A polymorphism in the leptin gene is associated with fasting leptin in patients with type 2 diabetes. The distribution of the genotypes in diabetic subjects from diabetic pedigrees differs from those in normal controls. The A allele frequency in diabetic patients is higher than that in normal controls. The haplotypes defined by genotypes are different in the familial subjects.     

Heme oxygenase-1 polymorphism associated with severity of chronic obstructive pulmonary disease

Background Recent studies have suggested that susceptibility to chronic obstructive pulmonary disease （COPD） might be related to the length polymorphism of （GT）n repeat in the 5＇-flanking region of heme oxygenase-1 （HOX-1） gene. However, there has been no research about the relationship between the polymorphism of HOX-1 gene and severity of COPD. Methods The polymorphism of HOX-1 gene in 452 patients with COPD from Han population in Southwest China was analysed by fragment analysis. The frequencies of the HOX-1 genotype were compared with the stage of COPD of each patient. Results The HOX-1 genotypes were classified into two groups： group I were individuals with class L allele （the number of GT 〉32 repeats）, and group II were those without class L allele （the number of GT 〈32 repeats）. The genotypic frequency of the HOX-1 group I was significantly higher than group II in the very severe COPD patients （36.8% vs 22.4%, P〈0.01, OR=2.0, 95% CI 1.3-3.1）, while the genotypic frequency of the HOX-1 group II was lower in the mild COPD （16.0% vs 26.0%, P=-0.02, OR=0.5, 95% CI 0.3-0.9）. However, in moderate and severe stages COPD, there were similar genotypic frequencies between HOX-1 group Ⅰ and group Ⅱ. Conclusions Genetic polymorphism in HOX-1 is associated with the severity of COPD in Southwest China. COPD patients with class L allele may be susceptible to develop very severe COPD. Conversely, the COPD patients without class L allele may be more easily stabilized on mild COPD.     

Gene polymorphism in apolipoprotein E and presenilin-1 in patients with late -onset Alzheimer’s disease

Objective To evaluate the association of apolipoprotein E (apoE) and presenilin-1 (PS-1) gene polymorphism with late-onset Alzheimer’s disease (AD). Methods A case-control study was undertaken to detect the polymorphism of apoE and PS-1 by polymerase chain reaction and digestion with the endonucleases of BspL Ⅰ, Hha Ⅰ and BamH Ⅰ. Results The frequencies of apoE ε3/4 genotype and ε4 allele in late-onset AD (n=42) were significantly higher than those of age-matched controls (P&lt;0.05). The frequencies of the apoE intron 1 enhancer (IE1) G/G genotype and G allele in late-onset AD were also significantly higher than those in controls (P&lt;0.05). The frequencies of the PS-1 1/1 genotype but not the 1 allele in AD were significantly higher than those in controls (P&lt;0.05).The apoE ε4 allele was associated with a tripling of risk for late-onset AD compared with that with no ε4 allele (odds ratio: 2.932). Homozygosity of the G allele in IE1 and 1/1 genotype in PS-1 was associated with a doubling of risk for late-onset AD, and odds ratios were 2.223 and 2.066, respectively.When the apoE ε4 was controlled, the association between the IE1 G/G genotype AD was no longer statistically significant (P&gt;0.05). We sequenced the exon 4 of apoE in patients with late-onset AD, and found no other genetic polymorphism or mutation except for apoE ε4 and IE1 G alleles associated with AD. Conclusion apoE ε4 gene appears to be the strongest gene risk factor for late-onset AD and its apparent association between the IE1 G/G genotype and late-onset AD is a consequence of the association between the ε4 and IE1 G/G genotype.The PS-1/1 genotype is weakly associated with late-onset AD.     

Association of G＋1688A Polymorphism of Platelet Endothelial Cell Adhesion Molecule-1 Gene with Myocardial Infarction in the Chinese Han Population

In order to investigate the association of G＋1688A （Ser563Asn） polymorphism of platelet endothelial cell adhesion molecule-1 （PECAM-1） gene with myocardial infarction （MI） in the Chinese Han population, the G＋1688A polymorphism in PECAM-1 gene was detected by polymerase chain reaction-restriction fragment-length polymorphism （PCR-RFLP） method among 502 subjects, including 218 patients with MI and 284 controls. The results showed that there was significant difference in AA frequencies of genotype G＋1688A polymorphism between case and control groups （39% vs 24%, P〈0.001）. A similar trend was observed on the allele frequencies （A/G： 62% vs 49%, P〈0.001）. Among the subjects with high serum total cholesterol level or high systolic blood pressure level, the variant AA genotype was associated with high risk of MI （adjusted OR, 2.13; 95% CI, 1.08 -4.41 and adjusted OR, 2.53; 95%CI, 1.63-3.63）. The single nucleotide polymorphism （SNP） at position ＋1688 in the exon 8 of PECAM-1 gene was associated with MI and the allele A might be a risk factor for MI in the Chinese Han population.     

Association of C（-106）T Polymorphism in Aldose Reductase Gene with Diabetic Retinopathy in Chinese Patients with Type 2 Diabetes Mellitus

Objective To identify the possible association between C（-106）T polymorphism of the aldose reductase （ALR） gene and diabetic retinopathy （DR） in a cohort of Chinese patients with type 2 diabetes mellitus （T2DM）. Methods From November 2009 to September 2010, patients with T2DM were recruited and assigned to DR group or diabetic without retinopathy （DWR） group according to the duration of diabetes and the grading of 7-field fundus color photographs of both eyes. Genotypes of the C（-106）T polymorphism （rs759853） in ALR gene were analyzed using the MassARRAY genotyping system and an association study was performed. Results A total of 268 T2DM patients （129 in the DR group and 139 in the DWR group） were included in this study. No statistically significant differences were observed between the 2 groups in the age of diabetes onset （P=0.10） and gender （P=0.78）. The success rate of genotyping for the study subjects was 99.6% （267/268）, with one case of failure in the DR group. The frequencies of the T allele in the C（-106）T polymorphism were 16.0% （41/256） in the DR group and 19.4% （54/278） in the DWR group （P=0.36）. There was no signit~cant difference in the C（-106）T genotypes between the 2 groups （P=0.40）. Compared with the wild-type genotype, odds ratio （OR） for the risk of DR was 0.7 （95% CI, 0.38-1.3） for the heterozygous CT genotype and 0.76 （95% CI, 0.18-3.25） for the homozygous TT genotype. The risk of DR was positively associated with microalbuminuria （OR=4.61; 95% CI, 2.34-9.05） and insulin therapy （OR=3.43; 95% CI, 1.94-6.09）. Conclusions Microalbuminuria and insulin therapy are associated with the risk of DR in Chinese patients with T2DM. C（-106）T polymorphism of the ALR gene may not be significantly associated with DR in Chinese patients with T2DM.     

Polymorphism of methionine synthase gene in nuclear families of congenital heart disease

Objective To investigate the relation of methionine synthase (MS) gene variation with congenital heart disease (CHD) phenotype. Methods One hundred and ninety three CHD patients (94 males and 99 females) and their biological parents (nuclear families) in Liaoning Province were selected as the case group, and another 104 normal persons (60 males and 44 females) and their parents without family history of birth defects as the control group. For all subjects the polymorphism of MS gene A2756G locus was examined by PCR-RFLP method. Results In offspring of the control group the frequencies of MS genotype ( / -) and allele ( ) were 10.7% and 5.3%, without existence of homozygote. The MS genotype distribution and allele frequencies of CHD patients and their mothers were not significantly different from the control (P > 0.05). The frequency of allele ( ) in case fathers (5.0 %) was apparently lower than that in the control (9.1%, P=0.060), and the odds ratio (OR) was 0.53 (95% CI: 0.25-1.09). There was no diffe     

Association of TNF-α-238G/A and 308 G/A Gene Polymorphisms with Pulmonary Tuberculosis among Patients with Coal Worker＇s Pneumoconiosis

Objectives Tumor necrosis factor-α （TNF-α） may play an important role in host＇s immune response to mycobacterium tuberculosis （M. tuberculosis） infection. This study was to investigate the association of TNF-α gene polymorphism with pulmonary tuberculosis （TB） among patients with coal worker＇s pneumoconiosis （CWP）. Methods A case-control study was conducted in 113 patients with confirmed CWP complicated with pulmonary TB and 113 non-TB controls with CWP. They were matched in gender, age, job, and stage of pneumoconiosis. All participants were interviewed with questionnaires and their blood specimens were collected for genetic determination with informed consent. The TNF-α gene polymorphism was determined with polymerase chain reaction of restriction fragment length polymorphism （PCR-RFLP）. Frequency of genotypes was assessed for Hardy-Weinberg equilibrium by chi-square test or Fisher＇s exact probability. Factors influencing the association of individual susceptibility with pulmonary TB were evaluated with logistic regression analysis. Gene-environment interaction was evaluated by a multiplieative model with combined OR. All data were analyzed using SAS version 8.2 software. Results No significant difference in frequency of the TNF-α-308 genotype was found between CWP complicated with pulmonary TB and non-TB controls （2,2=5.44, P=-0.07）. But difference in frequency of the TNF-α-308 A allele was identified between them （2,2-5.14, P=0.02）. No significant difference in frequencies of the TNF-α-238 genotype and allele （P=0.23 and P=0.09, respectively） was found between cases and controls either, with combined （GG and AA） OR of 3.96 （95% confidence interval of 1.30-12.09） at the -308 locus of the TNF-α gene, as compared to combination of the TNF-α-238 GG and TNF-α-308 GG genotypes. Multivariate-adjusted odds ratio of the TNF-α-238 GG and TNF-α-308 GA genotypes was 1.98 （95% CI of 1.06-3.71） for risk for pulmonary TB in patients with CWP. There was a synergic interaction between the TNF-a-308 GG genotype and body mass index （OR=4.92）, as well as an interaction between the TNF-α-308 GG genotype and history of BCG immunization or history of TB exposure. And, the interaction of the TNF-α-238 GG genotype and history of BCG immunization or TB exposure with risk for pulmonary TB in them was also indicated. Conclusions TNF-α-308 A allele is associated with an elevated risk for pulmonary TB, whereas TNF-α-238 A allele was otherwise.     

Association of angiotensin Ⅱ type 1 receptor gene polymorphism with essential hypertension

Objective To determine whether the polymorphism A1166C in the angiotensin Ⅱ type 1 receptor (AT1R) gene is associated with essential hypertension.Methods A case-control study was carried out using 125 hypertensive and 103 normotensive subjects. The A→C variant at position 1166 (A1166C) of t he AT1R gene was identified by polymerase chain reaction (PCR) and PCR/ restriction fragment length polymorphism (PCR/RFLP) analysis. The digestion products were separated on 2% agarose gels and visualized with ethid ium bromide under ultraviolet ray.Results The differences in C1166 allele frequency and in the AC genotype dist ribution of the AT1R gene between the hypertensive and normotensive groups were statistically significant (C allele: 0.092 vs 0.034, χ(2) =6.1 86, P&lt;0.05; AC genotype: 0.184 vs 0.068, χ(2) =6.654, P&lt;0.05).Conclusion The AC genotype is associated with essential hypertension, and the C a llele may be a marker for predisposition to hypertension in Chinese H an population.     

TUMOR NECROSIS FACTOR-ALPHA POLYMORPHISM AND SECRETION IN MYASTHENIA GRAVIS

Objective To analyze the relationship between tumor necrosis factor-alpha (TNFo) gene promoter -308 polymorphism and myasthenia gravis (MG) in Chinese and analyze secretion of TNFo in peripheral blood mononuclear cells (PBMC) in MG patients.Methods A biallelic polymorphism at position -308 in the promoter of TNFα gene was screened by PCR amplification and NcoI recognition site. One hundred and twenty-three MG cases and 115 healthy controls were included in this study. MG patients were classified to different groups according to clinical type, age at onset, and sex respectively. PBMC were isolated from 20 patients and 20 healthy controls, and then cultured in the presence or absence of phytohemagglutinin (PHA) and acetycholine receptors (AchR). The supernatants were harvested after incubation and stored until TNFαwas assayed by enzyme-linked immunosorbent assay.Results The frequency of TNFα-308 allele 2 (A) was found significantly increase in MG patients and showed a trend especially in late onset (≥ 40 years) and male patients (P ＜ 0.05). The allele A had no relationship with thymic pathogenesis in MG patients. But frequency of allele A was significantly higher in general type than in ocular type (P ＜ 0.05). MG patients had a higher inducible level of TNFα by PHA and AchR, and could be down regulated after treatment.Conclusion Polymorphism in TNFα gene promoter -308 is associated with onset of MG. The microsatellite allele TNFα2 confer risk for the development of MG in Chinese patients. MG patients have a higher inducible level of TNFα.     

Surfactant protein B 1580 polymorphism is associated with susceptibility to chronic obstructive pulmonary disease in chinese han population

Whether surfactant protein B (SP-B)-18A/C and 1580C/T polymorphism were associated with susceptibility to chronic obstructive pulmonary disease (COPD) in Chinese Han population和was investigated. After genomic DNA was isolated from blood of COPD smokers and control smokers, the genotypes of SP-B-18A/C and SP-B1580C/T polymorphism loci were determined by polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP) respectively.The results showed that there was significant difference in genotypes distribution frequency of SPB1580C/T polymorphism locus between COPD smokers and control smokers. C→T mutation rate (including TT homozygote and CT heterozygote) in COPD smokers was higher than in control smokers (57.9 % vs 41.7 %, X^2 =4.93, P＜0.05), whereas there was no significant difference in genotypes distribution frequency of SP-B1580-18A/C locus between COPD smokers and control smokers. The allele frequency (29.1 ％) of SP-B1580-18A/C locus is lower than T allele (70.9 ％) in Chinese Han Population, and the distribution was different from that in Mexican, in which, the A and T allele frequencies were 85 % and 15 % respectively. It was concluded that SP-B1580 T allele was probably associated with increased susceptibility to COPD in Chinese Han population; The polymorphism of SP-B-18A/C locus maybe varied with race.     

Association of IL33/ST2 Signal Pathway Gene Polymorphisms with Myocardial Infarction in a Chinese Han Population

This study investigated the relationship between IL-33/ST2 signal pathway gene polymorphisms and myocardial infarction(MI) in Han Chinese. A case-control association analysis was performed on a total of 490 MI patients(MI group) and 929 normal subjects(NC group). Sequenom Mass Array and Taqman genotyping technique were used to analyze the tag single nucleotide polymorphisms(SNPs) in the genes encoding IL-33, ST2, and IL-1Ra P(rs11792633, rs1041973 and rs4624606). The results showed that the frequencies of rs4624606 genotypes AA, TT, AT were 0.031, 0.647, 0.322 in MI group and 0.026, 0.712, 0.263 in NC group, and the allele frequencies of A and T were 0.192, 0.808 in MI group and 0.157, 0.843 in NC group. There were significant differences in rs4624606 genotypes and allele frequencies between MI group and NC group(P<0.05). For rs11792633, the allele frequencies of C and T were 0.45, 0.55 in MI group and 0.454, 0.546 in NC group with no significant differences found between the two groups. Compared with genotype CC+TC, rs11792633 genotype TT had an increased risk of hypertension(P<0.05). However, there were no significant differences in the frequencies of rs11792633 genotypes between the two groups. No significant differences were noted in the frequencies of rs1041973 genotype and allele between the two groups. Logistic regression analysis showed that rs4624606 genotypes AT and AA+AT were both significantly associated with MI(AT: OR=1.325, P=0.029, 95% CI=1.03–1.705; AA+AT: OR=1.316, P=0.028, 95% CI=1.03–1.681) after factors such as age, gender, smoking, drinking, body mass index(BMI), triglyceride(TG) and cholesterol were adjusted. Those carrying rs4624606 genotype AT or AA+AT had an increased risk of MI. No associations were found between the polymorphisms of the other two loci with MI. It was concluded that, in the IL33/ST2 signal pathway, the A allele of rs4624606 polymorphism of IL-1Ra P gene is a potential independent risk factor for MI, and the genotypes AA+AT and AT are associated with the incidence of MI.     

中国汉族人群中20p12染色体上三个单核苷酸多态性与后纵韧带骨化发生及其严重程度的关系研究

Background Ossification of the posterior longitudinal ligament （OPLL） is characterized by the replacement of ligamentous tissue with new ectopic bone formation, and has a strong genetic background. Because of the abnormal bone metabolic features and the strong genetic component, osteoporosis is a related disorder with OPLL. Three polymorphisms on chromosome 20p12 were identified associated with the risk of osteoporosis and osteoporotic fracture.The rs996544 （C/T） ＂TT＂ and rs965291 （G/A） ＂AA＂ genotypes conferred higher risks for vertebral and hip fractures. The osteoporosis haplotype is defined by two polymorphisms, rs1116867 （A） and D35548 （T）. However, it remains unknown whether these three polymorphisms predispose to an increased frequency and severity of OPLL in Han Chinese patients.Methods A total of 420 OPLL patients and 506 age- and sex-matched controls were studied. Three single nucleotide polymorphisms （SNPs）, rs996544 （C/T）, rs965291 （G/A） and rs1116867 （A/G）, were analyzed by direct sequencing.Associations between these SNPs with the occurrence and extent of OPLL were statistically evaluated.Results There was no significant association between the rs996544 （C/T） polymorphism and the prevalence of OPLL.The rs1116867 （A/G） polymorphism ＂AG＂ genotype was associated with the occurrence of OPLL. The rs1116867 （A/G） polymorphism ＂G＂ allele was associated with the occurrence of OPLL, but not with the extent of OPLL. The rs965291 （G/A） polymorphism in female patients was statistically different between cases and controls （P 〈0.05）. The rs965291 （G/A） polymorphism ＂A＂ allele was associated with the occurrence of OPLL in female patients. For the rs965291 （G/A）polymorphism, patients with the ＂A＂ allele （genotype, ＂AG＂ or ＂AA＂） showed a significantly greater number of ossified cervical vertebrae than those without the ＂A＂ allele （genotype, ＂GG＂, P 〈0.05）, particularly in female patients.Conclusions The rs1116867 （A/G） and rs965291 （G/A） polymorphisms on chromosome 20p12 are associated with the occurrence and the extent of OPLL, at least in Han Chinese subjects. Our data should advance our understanding of the molecular etiology of OPLL and may guide approaches to prevent the onset of OPLL.     

Lack of Association between rs4331426 Polymorphism in the Chr18q11.2 Locus and Pulmonary Tuberculosis in an Iranian Population

Objective The effect of rs4331426 polymorphism in the Chr18q11.2 locus on pulmonary tuberculosis (PTB) risk was evaluated.
Methods This case-control study included 208 PTB patients and 204 healthy subjects. Genotyping of the rs4331426 variant was conducted using polymerase chain reaction restriction fragment length polymorphism.
Results The frequencies of genotypes AA, AG, and GG polymorphisms were 83.1%, 15.9%, and 1.0% in the PTB group and 84.3%, 15.2%, and 0.5% in the control group, respectively. The frequency of the minor (G) allele was 8.9% in the PTB group and 8.1% in controls. Neither genotype nor allele frequencies of the rs4331426 variant showed statistically significant differences between PTB and controls. In addition, stratification by sex showed no significant association between the rs4331426 variant and PTB risk in males or females.
Conclusion In conclusion, the results of this study do not support an association between the rs4331426 polymorphism and risk of PTB in an Iranian population.     

Association between cholesteryl ester transfer protein gene polymorphisms and variations in lipid levels in patients with coronary heart disease

Background The Taq I B, Msp I and 1405V polymorphisms of cholesteryl ester transfer protein (CETP), an important regulatory factor of lipid metabolism, have been attracted much more attention by the researchers. In this study, we investigated the associations between these 3 polymorphisms of CETP gene and variations in plasma lipid and lipoprotein levels in patients with coronary heart disease (CHD). Methods Genomic DNA was extracted from leukocytes of 203 CHD patients and 100 control subjects using the salting out method. Genotyping of the CETP gene was performed using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques. Statistical analysis was conducted using the SPSS 10.0 software package. Results The distribution of allele and genotype frequencies of the Taq I B, Msp I, and 1405 Vpolymorphisms was similar in the CHD patient group and the control group. The B1B1 genotype of the Taq I B polymorphism was associated with significantly higher TC (P=0.039) and LDL-C (P=0.044) levels than the B2B2 genotype in CHD patients, and with significantly higher LDL-C (P=0.034) levels than the B2B2 genotype in controls. Homozygotes of the 1405V polymorphism exhibited significantly higher HDL-C levels than VV homozygotes among control subjects (P=0.023). In male CHD patients with unambiguously assigned haplotypes, B2-M2-V/B2-M2-1 patients demonstrated significantly higher HDL-C concentrations than B1-M2-V/B1-M2-1 (P=0.023) and B1-M2-V/B1-M2-V patients (P=0.047). Conclusions Genetic variations in the CETP gene may account for a significant proportion of the differences in plasma lipid and lipoprotein concentrations among the general population. The B1B1 genotype of the Taq I B polymorphism is probably a genetic risk factor for CHD in the study population.