Tumor necrosis factor alpha (TNF-α) polymorphisms in Chinese patients with Graves' disease

ObjectivesTumor necrosis factor alpha (TNF-α) may play a central role in the development of Graves' disease (GD). The aim of this study was to investigate the association of TNF-α polymorphisms with GD in Chinese population.Design and methodsGenomic DNA was extracted from peripheral blood lymphocyte of 436 GD patients and 316 control subjects. TNF-α polymorphisms at positions ? 308 (G-308A, rs1800629), ? 238 (G-238A, rs361525), and + 419 (G + 419A, rs3093661) were genotyped.ResultsThe distribution of TNF-α ? 238 and + 419 allelic frequencies between GD and control individuals was significantly different. Both the G alleles of TNF-α ? 238 (OR 2.385, 95%CI 1.359–4.184) and + 419 (OR 2.293, 95%CI 1.303–4.035) SNPs conferred higher risk of GD as compared with A alleles. No significant difference of ? 308 allelic frequency was observed. Further haplotype analysis revealed that the haplotype GGG was associated with an increased risk of GD (OR 1.554, 95%CI 1.125–2.146), whereas the haplotype GAA was found to be protective (OR 0.419, 95%CI 0.239–0.736).ConclusionsThis study demonstrated the association of TNF-α gene with GD in Chinese patients.     

Implication of CLU gene polymorphisms in Chinese patients with Alzheimer's disease

BackgroundClusterin (also called apolipoprotein J) has a potential central role in the pathogenesis of Alzheimer's disease (AD). Recently, two genome-wide association studies have identified three variants in CLU gene encoding clusterin associated with AD risk in Caucasians, while there are no studies on the association of CLU with AD risk in Asians.MethodsThe study investigated 324 sporadic late-onset AD (LOAD) and 388 healthy controls matched for sex and age in a Han Chinese population. Three common genetic variants (rs2279590, rs11136000 and rs9331888) in CLU gene were genotyped using MALDI-TOF mass spectrometry.ResultsThe minor allele (G) of the rs9331888 polymorphism within CLU was significantly associated with an increased risk of LOAD (OR = 1.39, 95% CI = 1.13–1.72, P = 0.002). Logistic regression analysis revealed that the rs9331888 polymorphism presented strong associations with LOAD in the dominant, recessive and additive models. No significant differences in genotype and allele frequencies of the rs2279590 and rs11136000 polymorphisms were found between LOAD patients and controls. Haplotype analysis identified a risk haplotype (CCG) (OR = 1.66) and a protective haplotype (CCC)(OR = 0.70).ConclusionsOur findings implicate CLU as a susceptibility gene for LOAD in Han Chinese.     

Matrix metalloproteinase 9 gene haplotypes affect left ventricular hypertrophy in hypertensive patients

BackgroundMatrix metalloproteinases (MMPs) are involved in cardiac remodeling and are encoded by genes showing genetic polymorphisms that have functional implications. We examined whether MMP-9 genetic polymorphisms are associated with hypertension and with left ventricular (LV) remodeling in hypertensive patients.MethodsWe studied 173 hypertensive patients and 137 age, race and gender matched healthy controls. Heart echocardiography was performed in all patients and the following MMP-9 genetic polymorphisms were analyzed: C^? 1562T (rs3918242), ? 90 (CA)_14–24 (rs2234681) and Q279R (rs17576). Haplo.stats analysis was used to assess whether MMP-9 haplotypes are associated with hypertension. Linear regression analysis was performed to assess whether MMP-9 haplotypes affect LV mass index (LVMI) and other echocardiography parameters.ResultsMMP-9 ? 90 (CA)_14–24 “HH” genotype (H allele defined by number of CA repeats ≥ 21) was associated with hypertension (P = 0.0085; OR = 2.321, 95% confidence interval = 1.250 to 4.309). While one MMP-9 haplotype (“C, H, Q”) protects against LVMI and end-diastolic diameter increases due to remodeling (P = 0.0490 and P = 0.0367), another MMP-9 haplotype apparently has detrimental effects over both parameters in hypertensive patients (“T, H, Q”, P = 0.0015 and P = 0.0057, respectively).ConclusionGenetic polymorphisms in MMP-9 gene may modify the susceptibility of hypertensive patients to LV remodeling. Further studies are necessary to examine whether these polymorphisms affect clinical events in hypertensive patients.     

Association of FAM13A polymorphisms with COPD and COPD-related phenotypes in Han Chinese

ObjectivesGenome-wide association studies (GWAS) and integrative genomics approaches have demonstrated significant associations between chronic obstructive pulmonary disease (COPD) and FAM13A polymorphisms in non-Asian populations. The aim of this study was to investigate whether FAM13A polymorphisms would be associated with COPD susceptibility and COPD-related phenotypes in a Chinese Han population.MethodsSeven single nucleotide polymorphisms (SNPs) (rs7671167, rs10007590, rs2869966, rs2869967, rs2045517, rs1903003, rs6830970) in FAM13A gene were genotyped in a case–control study (680 COPD patients and 687 controls). Allele frequencies and genotype distributions were compared between patients and controls. To estimate the strength of association, odds ratios (OR) (with 95% CI) were calculated and potential confounding variables were tested by using logistic regression analysis.ResultsStatistical analysis revealed that SNP rs7671167 was associated with COPD in former smokers with adjusted P-value of 0.026. Five SNPs (rs7671167, rs2869966, rs2869967, rs2045517, and rs6830970) were associated with FEV1/FVC ratio in the entire cohort and rs6830970 was associated with FEV1/FVC ratio in COPD cases (P range 0.003–0.034). Borderline associations with FEV1/FVC ratio were found for rs2869966, rs2869967 and rs2045517 among cases (P = 0.05). Six SNPs (rs7671167, rs2869966, rs2869967, rs2045517, rs1903003, rs6830970) showed strong linkage disequilibrium (r² ≥ 0.9). Four major haplotypes were observed but showed no significant difference between case and control groups (P = 0.2356, 0.1273, 0.6266 and 0.3006 respectively).ConclusionsThe current study suggests that the FAM13A locus might be a contributor to COPD susceptibility in Chinese Han population.     

SIRT1 variants are associated with aging in a healthy Han Chinese population

BackgroundAging is influenced by diverse environmental and genetic risk factors. The SIRT1 (silent information regulator 1) gene has been shown to regulate lifespan and aging in previous studies. We determined whether variation in the SIRT1 gene is associated with aging in healthy Chinese population.MethodsThe study population comprised 482 healthy, unrelated Chinese subjects, of which 246 were aging individuals from 60 to 91 years old, and 236 younger individuals from 35 and 59 years old. All subjects were from Shenyang, China. Two single-nucleotide polymorphisms (SNP) were analyzed: rs3758391 near the 5′ end of the SIRT1 gene; and rs4746720, in the 3′ untranslated region.ResultsDifferences in allele and genotype frequency were seen between the groups, with rs3758391/C more common than rs3758391/T in the aging subjects (odds ratio = 1.453, p = 0.026), and with rs3758391/CC more common than rs3758391/CT and rs3758391/TT in the aging subjects (odds ratio = 3.042, p = 0.027). For the 3′ SNP, rs4746720/C was more common than rs4746720/T in the aging subjects (odds ratio = 1.347, p = 0.022), and rs4746720/CC was more common than rs4746720/CT and rs4746720/CT in the aging subjects (odds ratio = 1.461, p = 0.049). The haplotype frequency distribution was also different, with haplotype CC more common in the older group (odds ratio = 1.63, p = 0.01).ConclusionThese results suggest that SIRT1 gene polymorphisms may add a new factor on the multifactorial genetic contributions to aging.     

Association of genetic variations in aromatase gene with serum estrogen and estrogen/testosterone ratio in Chinese elderly men

BackgroundSingle nucleotide polymorphism (SNP) rs2470152 of the gene CYP19A1 is associated with serum estradiol (E2) levels in Caucasian men. However, it remains to be verified if rs2470152 is the sole determinant accounting for the association. We determined whether 2 CYP19A1 SNPs tagging different haploblocks (rs2470152 and rs2899470) are associated with sex steroid levels in Chinese men.MethodSerum sex steroid level including E2, estrone (E1) and testosterone (T), of 1402 Chinese men aged ≥ 65 years were analyzed. Genotyping of the two CYP19A1 SNPs was performed using T_m-shift allele-specific PCR.ResultsSNP rs2899470 was significantly associated with serum E2, E1 levels and E2/T ratio (p < 0.001). However, SNP rs2470152 was only modestly associated with E2/T ratio (p = 0.023). Analysis of haplotype showed a significant association between C-G, T-T haplotype with serum E2/T ratio (p = 0.019 and p = 1 × 10^? 5, respectively). Similarly, E2 levels was also associated the T-T and T-G haplotypes (p = 1 × 10^? 5).ConclusionThe genetic variation of CYP19A1 was associated with circulating estrogen levels in Chinese elderly men. In addition, it revealed that haplotype of rs2899470 and rs2470152, rather than rs2899470 alone, was a better indicator for the serum E2/T ratio and E2 levels.     

Confirmation of top polymorphisms in hypertension genome wide association study among Han Chinese

BackgroundConfirmation of genome wide association (GWA) results in independent samples has recently become new research tendency.MethodsWe focused on 8 positive top polymorphisms identified in the to-date largest hypertension GWA study and determined whether these polymorphisms were associated with hypertension among Han Chinese. Genotyping was performed among 548 patients diagnosed with essential hypertension and 560 age- and gender-matched controls using ligase detection reactions method. Statistical analyses were conducted using Logistic regression and genotype risk score.ResultsExcept for a rare polymorphism (rs653178), no deviation from Hardy–Weinberg equilibrium was observed for genotype distributions of others. There was significant differences in the genotype/allele distribution (P = 0.006/P = 0.002) of rs16998073 in FGF5 (fibroblast growth factor 5) upstream and the allele distribution (P = 0.037) of rs16948048 in ZNF652 (zinc finger protein 652) upstream between hypertensive patients and controls. Strong significance was also noted under assumption of different genetic models for the two coalescent polymorphisms, even after controlling covariates of interest. For example, rs16998073 had a 72% increased risk for hypertension under the co-dominant model (95% confidence interval: 1.20–2.45; P = 0.003). However, construction of genetic risk scores on common polymorphisms did not reveal any significance with both hypertension and blood pressure, suggesting that contribution of these polymorphisms to hypertension moderate or small in magnitude.ConclusionsOur results implicate variation in FGF5 and ZNF652 gene upstream regions with altered susceptibility to hypertension in Han Chinese.     

Lack of association between cellular repressor of E1A-stimulated genes (GREG) polymorphisms and coronary artery disease in the Han population of North China

BackgroundPhenotypic switching of smooth muscle cells (SMCs) plays a critical role in the pathogenesis of atherosclerotic lesions such as coronary artery disease (CAD). Accumulating evidence demonstrates that a cellular repressor of E1A-stimulated genes (CREG) plays a role in the maintenance of the mature phenotype of vascular SMCs. We assessed the possible association between CREG and CAD in the Han population of North China.MethodsThe promoter region of CREG by direct sequencing was conducted in 48 subjects. Then SNP rs2995073 and another 4 tagSNPs (rs4657669, rs3767443, rs16859185, and rs3753921) were selected for the association study. All five selected SNPs were determined in 1161 patients with angiographically proven CAD and 960 controls with normal coronary angiograms to investigate the possible involvement of CREG in CAD.ResultsGenotype frequencies of the 5 polymorphisms were similarly distributed between CAD group and controls (P > 0.05). Further haplotype analysis also found no significant differences in the distributions between CAD group and controls (P > 0.05).ConclusionThis study did not show an association between common variants of CREG and CAD in the northern Chinese Han population.     

The association between miR-146a gene rs2910164 polymorphism and gastric cancer risk: A meta-analysis

PurposeStudies have demonstrated that single nucleotide polymorphisms (SNPs) in miRNAs may lead to varying functional outcomes by altering miRNAs expression, even leading to the development of cancers. The association between a single nucleotide polymorphism (SNP) in miR-146a rs2910164 and susceptibility to gastric cancer has been studied during the recent years, but the results are still inconclusive and inconsistent. We performed a meta-analysis to evaluate the relationship between miR-146a rs2910164 polymorphism and the risk of gastric cancer.Materials and methodsThe databases of PubMed, MEDLINE and Web of Science were searched for suitable studies. A total of 8 published case–control studies on miR-146a rs2910164 polymorphism and gastric cancer risk including 4308 cases and 6370 controls were included.ResultsOverall, significant association was observed between rs2910164 and gastric cancer risk in allele model (OR = 1.11, 95% CI = 1.02–1.21); homozygote model (OR = 1.26, 95% CI = 1.10–1.43) and dominant model (OR = 1.21, 95% CI = 1.09–1.34). Stratified analysis by ethnicity showed significant association between rs2910164 polymorphism and gastric cancer susceptibility in Asians (OR = 1.10, 95% CI = 1.00–1.23 for G vs. C; OR = 1.25, 95% CI = 1.09–1.43 for GG vs. CC; OR = 1.19, 95% CI = 1.07–1.33 for GG vs. GC+CC, respectively). When stratified by genotyping methods and sample size, increased gastric cancer risk was only observed with the method by TaqMan and the sample size more than 1000.ConclusionIn summary, this meta-analysis indicated that miR-146a rs2910164 polymorphism was associated with the susceptibility to gastric cancer, especially in Asian population.     

Polymorphisms of insulin-like growth factor binding protein-3 as a predictor for risk and patient survival in esophageal squamous cell carcinoma

Background and purposeGenetic single nucleotide polymorphisms (SNP) play a critical role in the development of esophageal squamous cell carcinoma (ESCC). The aim of this study is to investigate the associations between insulin-like growth factor binding protein-3 (IGFBP-3) gene polymorphisms and ESCC patients risk and survival after definitive chemoradiotherapy (CRT).Materials and methodsWe undertook a case-control study to analyze two IGFBP-3 polymorphisms (rs2854744 A > C and rs2854746 G > C) in an Han Chinese population, by extraction of genomic DNA from the peripheral blood of 110 ESCC patients treated with CRT and 128 control participants, and performed IGFBP-3 genotyping using DNA sequencing.ResultsThe obtained results indicated that overall, no statistically significant association was observed in rs2854746 G > C. However, rs2854744 A > C genotype was at increased risk of ESCCs (P = 0.032; odds ratio (OR) = 1.201, CI 95%:1.014–1.423). Moreover, rs2854744 A > C genotype ESCCs were more significantly common in patients with tumor size of >6 cm than A allele ESCC and in cases of lower T stage. Furthermore, ESCC patients with rs2854744CC genotype have the poorer CRT response and shorter survival time than GG + GC genotype ESCC.ConclusionsIn conclusion, polymorphism in IGFBP-3 rs2854744 A > C might be a potential predictor of ESCC risk and patient survival. Nevertheless, further investigation with a larger sample size is needed to support our results.     

Effects of common FTO gene variants associated with BMI on dietary intake and physical activity in Koreans

BackgroundAssociations with FTO (fat mass and obesity associated) gene variants and BMI have been reported in western adult populations. To widen the ethnic and age coverage of the FTO studies, we investigated the effects of FTO gene variants on being overweight and related phenotypes in Korean children and adult with a consideration of lifestyle factors.MethodsWe genotyped 711 children for 2 FTO SNPs (rs9939973 and rs9939609), analyzed lifestyle factors, and investigated the potential involvement of FTO variants in being overweight comparing with 8842 adults in the KSNP database.ResultsWith a strong association between FTO gene variants and BMI levels, we further identified an association between rs9939973 or rs9939609 and being overweight both children (P = 0.025, OR = 1.47, 95% CI = 1.05–2.06; P = 0.023, OR = 1.53, 95% CI = 1.06–2.22) and adults (P = 0.018, OR = 1.10, 95% CI = 1.02–1.19; P = 0.001, OR = 1.16, 95% CI = 1.06–1.27). Significant association was observed between rs9939609 and dietary fat intake in children (P = 0.008) but not in adults. In low physical activity subgroup of children, rs9939609 A allele carriers had a higher BMI than TT carriers (P = 0.0147). A significant interaction effect of rs9939609 on BMI across 3 levels of adult physical activity was found.ConclusionsFTO variant rs9939609 is an overweight susceptibility gene in Koreans. By low physical activity, A allele greatly influenced greater BMI.     

Association of STAT4 polymorphisms with susceptibility to primary membranous glomerulonephritis and renal failure

BackgroundMembranous glomerulonephritis (MGN) is one of common causes of idiopathic nephrotic syndrome in adults, and 25% of MGN patients proceed to end-stage renal disease. STAT4 gene polymorphisms have been reported to be associated with many inflammatory diseases. The objective of this study was to clarify the relationship between STAT4 gene polymorphisms and the pathogenesis of MGN.MethodsWe investigated the association of three STAT4 gene polymorphisms (rs3024912, rs3024908, and rs3024877) with the susceptibility to MGN in 403 Taiwanese populations (138 MGN patients and 265 controls).ResultsThe results indicated that the statistically significant difference in genotype frequency distribution was found at rs3024908 SNP in MGN patients and control groups (p = 0.014). In addition, the individuals with the GG genotype at rs3024912 SNP may have a higher risk in kidney failure of MGN patients (adjusted odds ratio [OR] = 3.255; 95% confidence interval [CI] = 1.155–9.176, p = 0.026).ConclusionsOur data provide a new information that the STAT4 (rs3024912 and rs3024908) polymorphisms may be the underlying cause of MGN, and these polymorphisms revealed by this study warrant further investigation.     

Common genetic polymorphisms in pre-microRNAs were associated with increased risk of dilated cardiomyopathy

BackgroundCommon single nucleotide polymorphisms (SNPs) in pre-microRNAs may change their property through altering microRNAs (miRNAs) expression and/or maturation, resulting diverse functional consequences. We conducted a pilot study to test whether SNPs in pre-microRNAs were associated with dilated cardiomyopathy (DCM).MethodsGenotypes of 3 SNPs in pre-miRNAs (has-mir-196a2 rs11614913 C/T, hsa-mir-499 rs3746444 A/G, hsa-mir-146a rs2910164 C/G) in 221 DCM patients and 321 control subjects were determined with the use of PCR-restriction fragment length polymorphism (RFLP) assay.ResultsSignificantly increased DCM risks were found to be associated with variant allele of has-mir-196a2 rs11614913 C/T (T allele) and hsa-mir-499 rs3746444 A/G (G allele) (P < 0.0001, OR = 1.730, 95% CI = 1.345–2.227, and P < 0.0001, OR = 1.794, 95% CI = 1.350–2.385, respectively). We found that increased DCM risk was statistically significantly associated with these 2 SNPs in a dominant model (P = 0.0001 and P < 0.0001 for rs11614913 and rs3746444, respectively). No association between DCM risk and hsa-mir-146a rs2910164 C/G was observed (P = 0.451, OR = 1.102, 95% CI = 0.856–1.418).ConclusionsBoth the has-mir-196a2 rs11614913 C/T and hsa-mir-499 rs3746444 A/G, but not hsa-mir-146a rs2910164 C/G, are associated with a significantly increased risk of DCM, indicating that common genetic polymorphisms in pre-microRNAs are associated with DCM.     

Methionine sulfoxide reductase A rs10903323 G/A polymorphism is associated with increased risk of coronary artery disease in a Chinese population

ObjectiveCoronary artery disease (CAD) is a complex disease resulting from a combination of environmental and genetic factors. We hypothesized that polymorphisms in methionine sulfoxide reductase A (MSRA: rs10903323 G/A) and vascular endothelial growth factor A (VEGFA: rs699947 C/A, rs2010963 G/C, and rs3025039 C/T) contribute to CAD susceptibility.Designs and methodsWe examined the association between the four polymorphisms and the risk of CAD in a Chinese population of 435 CAD patients and 480 controls. Genotyping was performed using matrix-assisted laser desorption ionization/time-of-flight mass spectrometry (MALDI/TOF-MS).ResultsWhen the MSRA rs10903323 GG homozygous genotype was used as the reference group, the GA and GA/AA genotypes were associated with a significantly increased risk of CAD (GA vs GG: adjusted OR = 1.36, 95% CI = 1.02–1.82, p = 0.038; GA/AA vs GG: adjusted OR = 1.33, 95% CI = 1.01–1.76, p = 0.042). The AA homozygous genotype was not associated with a risk of CAD. In the recessive model, when the MSRA rs10903323 GG/GA genotypes were used as the reference group, the AA homozygous genotype was not associated with a risk of CAD. Logistic regression analyses revealed that the VEGFA rs699947 C/A, VEGFA rs2010963 G/C, and VEGFA rs3025039 C/T polymorphisms were not associated with a risk of CAD.ConclusionsThese findings suggest that the functional MSRA rs10903323 G/A polymorphism is associated with CAD development. However, our results allow only a preliminary conclusion, which must be validated with a larger study of a more diverse ethnic population.     

Genetic variation in C12orf51 is associated with prognosis of intestinal-type gastric cancer in a Chinese population

Recent genome-wide association study (GWAS) on esophageal squamous-cell carcinoma (ESCC) among Chinese population has identified two novel single nucleotide polymorphisms (SNPs) rs11066280 and rs2074356 on C12orf51 gene. We hypothesized that SNPs rs11066280 and rs2074356 could influence gastric cancer survival outcomes. We genotyped the SNPs rs11066280 and rs2074356 in 940 patients with surgically resected gastric cancer. Analyses of genotype association with survival outcomes were assessed by the Kaplan-Meier method, Cox proportional hazards models and the log-rank test. There was no significant association between rs11066280 and survival of gastric cancer. However, in the stratification analysis of histology, we found that the rs11066280 TA/AA genotypes were associated with a poor survival of intestinal-type gastric cancer (log-rank P = 0.041, hazard ratio [HR] = 1.40, 95% confidence interval [CI] = 1.02–1.93), Moreover, this hazardous effect was more prominent among patients with tumor size > 5 cm, no distant metastasis, chemotherapy and drinking. No significant association was observed between rs2074356 and the survival of gastric cancer. C12orf5 rs11066280 could be useful marker of survival assessment and individualized clinical therapy for gastric cancer, particularly among the intestinal-type gastric cancer.     

Association of MTHFR, MTR, and MTRR polymorphisms with Parkinson's disease among ethnic Chinese in Taiwan

BackgroundInfluence of folate/homocysteine conversion is considered to be important in the pathogenesis of Parkinson's disease (PD). However, association of the folate metabolic pathway gene polymorphisms with PD susceptibility remains unclear.MethodsTo test this possibility in PD, we conducted a hospital-based case-control study constituting 211 patients and 218 age- and sex-matched controls of ethnic Chinese in Taiwan. Genotyping assay was performed to screen for polymorphisms of the methylenetetrahydrofolate reductase (MTHFR C677T), methyltetrahydrofolate-homocysteine methyltransferase (MTR A2756G), and 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR A1049G and C1783T) genes and assess the association between these genotype polymorphisms and PD risk using logistic regression analysis.ResultsOf these four non-synonymous polymorphisms, the MTRR 1049GG variant was significantly associated with PD susceptibility (OR = 3.17, 95%CI = 1.08–9.35). Furthermore, we stratified our patients based on the MTHFR 677TT genotype in different strata, a significant association between the joint effect of polymorphisms and PD risk was observed in those patients whose genotypes were MTRR A1049G/MTR A2756G or MTRR C1783T/MTR A2756G (P < 0.05).ConclusionOur findings provide support for the synergistic effects of polymorphisms in the folate metabolic pathway genes in PD susceptibility; the increased PD risk would be more significant in carriers with the polymorphisms of MTHFR, MTR, and MTRR genes.     

Association of rs2781666 G/T polymorphism of arginase I gene with myocardial infarction in Tunisian male population

ObjectivesThe aim of this study was to investigate the association between rs2781666 G/T polymorphism of arginase I (ARG I) gene and myocardial infarction (MI) in the Tunisian male population.Design and methodsThree hundred eighteen patients with MI and 282 controls were recruited. The rs2781666 G/T polymorphism of ARG I was determined by PCR-RFLP analysis.ResultsPatients had significantly higher frequency of TT genotype compared to controls (10.4% vs. 6.7%; p < 0.001). The MI patients showed higher frequency of T allele compared to the controls [0.33 vs. 0.22; OR (95% CI), 1.79 (1.37–2.34), p < 0.001]. The association between rs2781666 G/T polymorphism of ARG I gene and MI remained significant after adjustment for other well-established risk factors.ConclusionA significant association between rs2781666 G/T polymorphism of ARG I gene and MI was found in the Tunisian male population.     

Association of the MS4A2 gene promoter C-109T or the 7th exon E237G polymorphisms with asthma risk: A meta-analysis

Background and objectiveA large number of studies have examined the association between the Membrane-spanning 4 domains, superfamily A, number 2 (MS4A2) gene C-109T (rs1441586) or E237G (rs569108) variants and asthma risk. However, the results are inconsistent and inconclusive. To derive a more precise estimation, a meta-analysis was performed.MethodsMeta-analyses were conducted with the data from case–control association studies (24 studies with 4496 asthmatics and 4571 controls for E237G variant and 9 studies including 2005 cases and 1868 control for C-109T polymorphisms, respectively). Random-effects model was used to calculate summary odds ratios (ORs).ResultsFor the MS4A2 gene E237G variant, no significant associations with asthma were found in overall population; we observed an elevated risk of atopic asthma among subjects with the 237G allele (OR = 1.341, 95% CI: 1.039–1.732 for G versus E and OR = 1.374, 95% CI: 1.032–1.828 for EG + GG versus EE) in the stratified meta-analysis. As for the MS4A2 gene C-109T polymorphism, no significant associations with asthma risk were observed in the total population; in subgroup analysis by ethnicity of subjects we found increased asthma risk among Asians carrying T allele (OR = 1.140, 95% CI: 1.019–1.276 for T versus C and OR = 1.359, 95% CI: 1.029–1.794 for TT versus CC).ConclusionsData indicated that the MS4A2 gene E237G variant may be a risk factor for developing atopic asthma and the promoter -109T allele is a potential risk factor of asthma in Asians.     

Minor association of kinase insert domain-containing receptor gene polymorphism (rs2071559) with myocardial infarction in Caucasians with type 2 diabetes mellitus: Case–control cross-sectional study

ObjectiveVascular endothelial growth factor A (VEGF) and its receptor KDR play central roles in angiogenesis and vascular repair, which occur in diabetic vascular complications, such as MI. The aim of our study was to investigate if polymorphisms rs2071559 and rs2305948 in the kinase insert domain-containing receptor (KDR) gene are associated with myocardial infarction (MI) in Caucasians with type 2 diabetes (T2DM).Design and methodsThe association of KDR − 604T>C (rs2071559) and 1192G>A (rs2305948) polymorphisms was tested in a case–control cross-sectional study including 171 subjects with T2DM and MI compared to 855 subjects with T2DM without coronary artery disease (CAD). In addition, VEGF serum levels were analyzed in 98 subjects with type 2 diabetes without CAD.ResultsA significantly higher frequency of the CC genotype of the KDR − 604T>C (rs2071559) polymorphism was found in diabetic patients with MI compared to diabetic patients without CAD (27.5% vs. 21.1%, p = 0.04). On the other hand, the 1192G>A (rs2305948) polymorphism was not associated with MI in subjects with type 2 diabetes. Significantly higher VEGF serum levels were found in subjects with the − 604CC genotype compared to those with other (CT + TT) genotypes (73.8 ± 22.1 ng/l vs. 58.1 ± 18.5 ng/l; p < 0.01). Multiple logistic regression analysis adjusted for age, arterial hypertension, LDL cholesterol, HDL cholesterol and hsCRP revealed that carriers of the − 604CC genotype (rs2071559) had a 1.6-fold higher risk for MI (OR = 1.6; 95% CI = 1.1–2.1; p = 0.022).ConclusionThe present study demonstrates that the CC genotype of the KDR − 604T>C polymorphism (rs2071559) is a possible risk factor for MI in Caucasians with T2DM.     

Association between an ASIC3 gene variant and insulin resistance in Taiwanese

BackgroundAcid-sensing ion channel 3 (ASIC3) is a ligand-gated cation channel activated by extracellular protons. ASIC3^?/? mice exhibit protection against age-dependent glucose intolerance with enhanced insulin sensitivity.MethodsTo determine the association between ASIC3 genetic polymorphisms and insulin resistance in Taiwanese, 606 unrelated subjects with no history of cardiovascular disease were recruited during routine health examinations.ResultsSix ASIC3 gene polymorphisms were genotyped and only the rs2288646 polymorphism was found associated with insulin resistance. Significantly lower fasting serum insulin levels and homeostasis model assessment of insulin resistance (HOMA-IR) index and significantly higher quantitative insulin sensitivity check index (QUICKI) were observed in subjects carrying the rs2288646-A allele than in the non-carriers (P = 0.028, P = 0.047 and P = 0.031, respectively) after adjustment for age, gender, and body mass index (BMI). Significantly lower frequencies of the rs2288646-A-containing genotypes were found in insulin resistant subjects (P = 0.023). By multivariate analysis, rs2288646 genotypes, age, BMI, fasting plasma glucose level, C-reactive protein level, and soluble intercellular adhesive molecule 1 level, were all independently associated with HOMA-IR index and QUICKI (all, P < 0.05).ConclusionsOur analysis indicated an independent association between an ASIC3 genetic polymorphism and insulin resistance in Taiwanese.