Effect of obesity on the association between ATF3 gene haplotypes and C-reactive protein level in Taiwanese

ObjectiveATF3 has traditionally been related to various inflammatory processes. Our aim was to test the statistical association between variations in the ATF3 gene and levels of nine serum inflammatory markers, including C reactive protein (CRP), in a Taiwanese population using interaction analysis.MethodsA sample population of 604 Taiwanese subjects was enrolled. Five tagging single nucleotide polymorphisms of the ATF3 gene from the Han Chinese HapMap Database were selected and genotyped.ResultsWith or without adjustment for clinical covariates, ATF3 genotypes were found to be associated with CRP levels but not with other inflammatory marker levels. Minor alleles of 2 of the 5 ATF3 SNPs were associated with decreased CRP levels predominantly in non-obese subjects (Bonferoni P = 0.018, and P = 0.002 for rs11571530, and rs10475, respectively). Two haplotypes inferred from the 5 SNPs, GATTA and TACCA, were also associated with increased or decreased CRP levels, respectively, in non-obese subjects (Bonferoni P = 0.012 and P = 0.01, respectively) but not in obese subjects. Interaction analysis revealed interaction of obesity with an ATF3 genotype associated with a high CRP level (interaction P = 0.006 for SNP rs10475). An effect of obesity on CRP level was also noted in haplotype interaction analysis (interaction P = 0.019 for haplotype TACCA).ConclusionsATF3 polymorphisms are independently associated with CRP levels in Taiwanese subjects. Further, ATF3 genotypes/haplotypes interact with obesity to set CRP levels. These findings may have implications for the prediction of atherosclerotic disease.     

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.     

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.     

Polymorphism at the mucin-like protocadherin gene influences susceptibility to gallstone disease

BackgroundGallstone disease (GSD) is a common disease that can be caused by environmental influences, common genetic factors and their interactions. Mucin glycoproteins may be one important factor for GSD. We conducted a case–control study to investigate the relationship between the mucin-like protocadherin (MUPCDH) gene polymorphisms and GSD.MethodsThe study included 452 GSD cases and 491 healthy controls who had no evidence of gallstones by ultrasound examination. Two common tagging single nucleotide polymorphism (SNP) rs3758650 and rs7932167, and four non-synonymous SNPs rs34362213, rs2740375, rs7108757 and rs2740379 were genotyped. The genetic effects were evaluated using the multivariate regression model.ResultsThe genotypes of these SNPs were all in Hardy–Weinberg equilibrium. Three non-synonymous SNPs (rs34362213, rs7108757 and rs2740379) were monomorphic. The single SNP analysis showed two SNPs (rs7932167 and rs2740375) were not associated with GSD and only SNP rs3758650 had the association of the presence of GSD with an odds ratio (OR) of 1.59 (adjusted P = 0.013) for the AG genotype and 5.82 (adjusted P = 0.007) for the AA genotype when compared with the reference GG genotype. The haplotype analysis of the three polymorphic SNPs showed GCA was significant for GSD (adjusted p = 0.001) with an odds ratio (OR) of 1.41 when compared to other haplotypes.ConclusionsThe MUPCDH genetic polymorphism rs3758650 was considered a genetic marker to predict symptomatic GSD subjects. It may be of importance for GSD patients with the risk SNPs to be frequently checked because they may develop symptomatic GSD.     

A genetic variant in the gene encoding adrenomedullin predicts the development of dysglycemia over 6.4 years in Chinese

BackgroundAdrenomedullin, a vasodilatory peptide, facilitates the differentiation of pre-adipocytes, and affects lipolysis and glucose uptake. We investigated the association of common single nucleotide polymorphisms (SNPs) in the gene encoding adrenomedullin (ADM) with dysglycemia in the Hong Kong Chinese population.MethodsFour SNPs were genotyped in 1391 subjects without dysglycemia at baseline from the Hong Kong Cardiovascular Risk Factor Prevalence Study-2, which had a median follow-up time of 6.4 years. Dysglycemia included impaired fasting glucose, impaired glucose tolerance, and diabetes according to the WHO 1998 criteria. At follow-up, 382 subjects had developed dysglycemia.ResultsIn stepwise logistic regression, the SNP rs11042725 was a significant independent predictor of the development of dysglycemia (OR = 1.31, P = 0.012), together with baseline age (P < 0.001), plasma triglycerides (P < 0.001), body mass index (P = 0.004), 2-h glucose after oral glucose tolerance test (P < 0.001), homeostasis model assessment of insulin resistance index (P = 0.045), and follow-up duration (P = 0.009). The association was more significant in women (P = 0.002) and in subjects without regular exercise (P = 0.001).ConclusionsOur study suggests a potential role of genetic variants in the ADM gene in the development of dysglycemia in our local Chinese population.     

Multiple mucin genes polymorphisms are associated with gallstone disease in Chinese men

BackgroundGallstone is a complex disease caused by multiple environmental and genetic factors. One of these is mucin glycoproteins. This case–control study aimed to investigate the association between single nucleotide polymorphisms (SNPs) at the MUC1-4 genes and gallstone.MethodsThe study included 475 cases and 941 controls. Eight tagging SNPs were selected: one at MUC1, two at MUC2, and five at MUC4. There was no available tagging SNP at MUC3. Genetic effects were initially evaluated by multivariate logistic regression. The combined effects from multiple genes were further evaluated, as well as the sex-specific effect. Permutation was used to correct for multiple testing.ResultsThe genotypes were all in Hardy–Weinberg equilibrium. SNP rs7396030 at MUC2 yielded a p value of 0.03. Further sex-specific analysis showed significance solely with male subjects (p = 0.005). Similarly, SNP rs4072037 at MUC1 was only significant (p = 0.035) in males. The permutation empirical p values were 0.005 for rs7396030 and 0.02 for rs4072037. For males, the combined genetic effect yielded an OR of 4.68 (p = 0.0008).ConclusionsThe SNPs at MUC1 and MUC2 are significantly associated with gallstone in men but not in women. These genes can work jointly to further increase susceptibility to gallstone in a Chinese population.     

Common variant in GAB2 is associated with late-onset Alzheimer's disease in Han Chinese

BackgroundGRB-associated binding protein 2 (GAB2) may function as a risk factor in the pathogenesis of Alzheimer disease (AD). A recent large genome-wide association study (GWAS) has identified a significant association of rs10793294 polymorphism within the GAB2 gene with AD in Caucasians. While there are no studies on the association of rs10793294 polymorphism with AD risk in the Chinese population.MethodsThe study investigated 358 sporadic late-onset AD (LOAD) and 366 healthy controls matched for sex and age in a Han Chinese population. The rs10793294 polymorphism within the GAB2 gene was genotyped using MALDI-TOF mass spectrometry.ResultsThe C allele of the rs10793294 polymorphism within GAB2 was significantly associated with an increased risk of LOAD (OR = 1.33, 95% CI = 1.04–1.72, P = 0.029). Significance was observed in APOEε4 carriers (genotype P = 0.039, allele P = 0.016). While in APOE ε4 non-carriers, significant differences were observed in alleles (P = 0.039) but not in genotypes (P = 0.304). Logistic regression revealed that rs10793294 polymorphism was still strongly associated with LOAD in dominant model (OR = 2.58, 95% CI = 1.22–5.45, P = 0.013) and additive model (OR = 1.38, 95% CI = 1.05–1.80, P = 0.020) after adjusting for age, gender, and the APOE ε4 status.ConclusionsOur findings implicate GAB2 as a susceptibility gene for LOAD in Han Chinese.     

Functional glutathione peroxidase 3 polymorphisms associated with increased risk of Taiwanese patients with gastric cancer

BackgroundGlutathione peroxidase 3 (GPX3) can enhance an antioxidant's capacity and reduce genomic damage caused by oxidants and thus influence tumorigenesis. We investigated the role of GPX3 as a risk of gastric cancer.MethodsWe first conducted a case-control study to test for the association between 5 tagging single nucleotide polymorphisms (SNPs) of GPX3 and the risk of gastric cancer in Chinese. Multivariate logistic regression analysis was performed to estimate the genetic effect with adjustments for age and sex. Functional studies were performed by using the luciferase reporter assay to assess functional consequences of the significant SNPs.ResultsAmong five SNPs (rs3763013, rs8177412, rs3805435, rs3828599, and rs2070593) genotyped in 227 cases and 844 controls, 3 SNPs were significant: intronic SNP rs3805435 (OR = 0.70, P = 0.037), intronic SNP 3828599 (OR = 0.68, P = 0.025), and 3′ UTR SNP rs2070593 (OR = 0.48, P = 0.001). The two intronic SNPs rs3805435 and SNP rs3828599 were in linkage disequilibrium (D′ = 0.91).ConclusionsThe reporter assays showed significant difference in the luciferase expression between protective and risk alleles of 2o intronic SNPs (P = 0.004), whereas the 3′UTR SNP did not influence the luciferase expression. The intronic SNPs at GPX3 can influence gene expression leading to an alteration of gastric cancer risk.     

RAD51 gene is associated with advanced age-related macular degeneration in Chinese population

ObjectivesThis study aims to investigate whether variations in RAD51, B3GALTL, TNFRSF10A and REST-C4ORF14-POLR2B-IGFBP7 are associated with advanced forms of age-related macular degeneration (AMD) in Chinese population.Design and methodsA total of 119 Chinese patients with AMD and 99 control individuals were recruited. Genomic DNA was extracted from peripheral blood leukocytes. Seven single nucleotide polymorphisms (SNPs) from CFH, HTRA1, RAD51, B3GALTL, TNFRSF10A and REST-C4ORF14-POLR2B-IGFBP7 were genotyped by polymerase chain reaction (PCR) followed by allele-specific restriction enzyme digestion or SNaPshot.ResultsRs10483810 in RAD51 was significantly associated with advanced AMD (P = 0.045). Compared with the wild-type genotype GG, the odds ratio for the risk of advanced AMD was 4.92 (95% confidence interval: 1.04–23.36) for the heterozygous TG genotype. Moreover, the GT genotype at rs10483810 confers significantly increased risk of bilateral AMD compared to unilateral AMD (OR = 12.04, 95% CI: 2.50–57.69, P = 0.002). Rs13278062 in TNFRSF10A, rs1713985 in REST-C4ORF14-POLR2B-IGFBP7 and rs9542236 in B3GALTL were not found to be associated with AMD (all P > 0.05).ConclusionOur data suggested that the risk allele T of rs10483810 in RAD51 gene is associated with an increased risk of advanced AMD, especially bilateral AMD, in Chinese population.     

ChREBP gene polymorphisms are associated with coronary artery disease in Han population of Hubei province

BackgroudChREBP regulates lipogenesis and glucose utilization in the liver. Current reports suggest a contradictive association between rs3812316 of this gene and triglyceride level. We hypothesized the polymorphisms in ChREBP gene were associated with CAD in Chinese population.MethodsThe ChREBP gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods in 200 controls and 310 CAD patients. Serum lipids and glucose concentrations were measured in all subjects. Haplotypes were constructed based on rs3812316, rs7798357 and rs1051921. All the data were analyzed using SPSS14.0, PLINK1.07 and SHEsis software.ResultsThe rare allele G of rs3812316 was significantly lower in the CAD group after adjusting for age, sex, BMI, SBP and DBP (OR^a = 0.589, 95%CI = 0.361–0.961, P = 0.034). No significant differences between cases and controls were found in genotype or allele distributions of rs7798357, rs17145750 and rs1051921. Haplotype CGC was significant higher in CAD group (P < 0.01, OR = 2.364, 95%CI = 1.608–3.474), while haplotypes GGC, CGT, CCC were significant lower in CAD group (P < 0.05).ConclusionsThe rs3812316 and the haplotypes in ChREBP gene appeared to be related to high susceptibility to CAD.     

A single nucleotide polymorphism in LRP2 is associated with susceptibility to Alzheimer's disease in the Chinese population

BackgroundLRP2 (also called megalin) plays a potential key role in the pathogenesis of Alzheimer's disease (AD). Recently, one genome-wide association study has revealed that the rs3755166 (G/A) polymorphism located in the LRP2 promoter is associated with development of AD in Caucasians, while there are no studies on the association LRP2 of with AD risk in Asians.MethodsTo evaluate the relationship between the rs3755166 polymorphism of the LRP2 gene and AD in the ethnic Chinese Han, we conducted a case-control study (n = 361, age > 50) to determine the prevalence of one common single-nucleotide polymorphism (SNP) of LRP2 (rs3755166) in patients with AD in Chinese population of Mainland China, and clarified whether this polymorphism is a risk factor for AD.ResultsThe prevalence of the minor allele (A) in the rs3755166 polymorphism was significantly different in AD patients and control subjects (P < 0.05). The rs3755166 polymorphism was associated with AD in the ethnic Chinese Han (OR = 1.378, 95% CI: 1.017-1.867, P = 0.039), and the results were not influenced by age, gender, or APOE status (P = 0.441, P = 0.94, P = 0.432, respectively).ConclusionOur data revealed the allele (A) of the rs3755166 polymorphism within LRP2 gene may contribute to AD risk in the Chinese Han Population.     

Potential role of GABAA receptor subunit; GABRA6, GABRB2 and GABRR2 gene polymorphisms in epilepsy susceptibility and pharmacotherapy in North Indian population

BackgroundGABA_A receptors influence the susceptibility to seizures, and variations in the receptor genes can contribute to antiepileptic drug resistance also.MethodsWe investigated the possible associations of single nucleotide polymorphisms (SNPs) present in GABRA6 c. 1512 T>C, GABRB2 c. 1412 C>T, and GABRR2 c. IVS2C>G genes of GABA_A receptors in epilepsy susceptibility and drug resistance in northern Indian patients with epilepsy. After screening a total of 202 healthy controls and 401 epilepsy patients were enrolled in study. The genotyping was done by PCR-RFLP methods.ResultsThe GABRA6 c. 1512 T>C, polymorphism was conferring risk for epilepsy susceptibility for TC (P = 0.018), CC (P = 0.0001) genotype and for C allele (P = 0.0002). Another polymorphism GABRB2 c. 1412 C>T was also conferring high risk for epilepsy susceptibility CT (P = 0.012), TT (P = 0.778) genotype and for variant T allele (P = 0.034) but was not associated with drug resistance. No association was found with epilepsy susceptibility or with drug resistance in case of GABRR2 c. IVS2C>G gene polymorphism.ConclusionOverall, our findings suggest significant involvement of alpha (GABRA6) and beta (GABRB2) subunits of GABA_A receptor in epilepsy susceptibility in north Indian population.     

Folate and choline metabolism gene variants and development of uterine cervical carcinoma

ObjectiveIt has been reported that aberrant DNA methylation can be associated with HPV infection and cervical tumorigenesis. The aim of this study was to evaluate the possibility that polymorphic variants of genes that may affect DNA methylation status are associated with the risk of cervical cancer in the Polish population.Design and methodEmploying PCR-RFLPs and HRM analyses, we examined the prevalence of BHMT Arg239Gln (rs3733890), MTR Asp919Gly (rs1805087), MTHFR Ala222Val (rs1801133), MTHFD1 Arg653Gln (rs2236225) and MTRR Ile22Met (rs1801394) genotypes and alleles in patients with advanced cervical cancer (n = 124) and controls (n = 168).ResultsThe odds ratio (OR) for BHMT Gln/Gln genotype was 0.433 (95% CI = 0.1780–1.054; p = 0.0602). The OR for patients having the BHMT Arg/Gln or Gln/Gln genotypes was 0.579 (95% CI = 0.3622–0.924; p = 0.0216). We also observed a significantly higher frequency of the BHMT 239Gln allele in controls than in patients, p = 0.0165. The genotype and allele frequencies of the MTR Asp919Gly, MTHFR Ala222Val, MTHFD1 Arg653Gln and MTRR Ile22Met gene variants did not display statistical differences between patients with cervical cancer and controls. We also did not find a significant association between the distribution of any genotypes or alleles and cancer characteristics.ConclusionOur results might suggest the protective role of the BHMT 239Gln variant in cervical cancer incidence.     

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.     

Programmed death-1 (PD-1) polymorphisms in Chinese patients with esophageal cancer

ObjectivesEsophageal cancer is an extremely aggressive gastrointestinal malignancy, which appears to result from a complex interplay between genetic and environmental agents. The genetic loci conferring susceptibility have yet to be fully defined. Considering the role of programmed death-1 (PD-1) in immune regulation and tumor pathogenesis, we genotyped three functional single nucleotide polymorphisms (SNPs) in PD-1 in a Chinese population to explore whether these three SNPs confer susceptibility to esophageal cancer.Design and methodsA total of 629 new diagnosed esophageal squamous cell carcinoma (ESCC) cases and 686 controls were recruited for this hospital-based case–control study. Genotyping was performed by the polymerase chain reaction–ligase detection reaction (PCR–LDR) method in all the subjects.ResultsIn the recessive model, when the PD-1 rs10204525 AA/AG genotypes were used as the reference group, the GG homozygote genotype was associated with a borderline statistically decreased risk of ESCC [adjusted odds ratio (OR) = 0.68, 95% confidence interval (CI) = 0.45–1.03, P = 0.067]. However, there were no significant associations between the other two SNPs and ESCC risk. Stratified analyses showed that a significantly decreased risk of ESCC associated with PD-1 rs10204525 A > G polymorphism was overt among male and younger patients.ConclusionsOur results demonstrate for the first time that the PD-1 rs10204525 polymorphism might contribute to susceptibility of ESCC and may therefore support the hypothesis that genetic variants, influencing T cell activity-associated gene regulation, may modify cancer risk.     

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.     

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.     

Genetic association of rs11610206 SNP on chromosome 12q13 with late-onset Alzheimer's disease in a Han Chinese population

BackgroundSeveral genome wide screens and candidate gene studies have implicated the chromosome 12p13 locus as possibly harboring genetic variants predisposed to late-onset Alzheimer's disease (LOAD). Recently, the strongest significant association was reported for the single nucleotide polymorphism (SNP) rs11610206 on chromosome 12q13 in an independent genome-wide association study (GWAS) in Caucasians.MethodsWe investigated whether the SNP on chromosome 12q13 was associated with LOAD in a Han Chinese population. The common rs11610206 SNP on chromosome 12q13 was genotyped using MALDI-TOF mass spectrometry in 322 patients with LOAD and in 391 healthy controls matched for sex and age.ResultsPatients with LOAD had higher frequencies of T allele (56.0% versus 49.2%) compared with controls [odds ratio (OR) = 1.45, 95% confidence intervals (CI) = 1.08–1.95, and P = 0.01]. After stratification by APOE ε4-carrying status, the T allele of rs11610206 was significantly associated with LOAD only in APOE ε4 allele carriers (OR = 2.05, 95% CI = 1.21–3.47, and P = 0.007). Furthermore, multivariate logistic regression analysis showed that the TT genotype carriers demonstrated a 1.52-fold risk when compared with (TC + CC) genotype carriers (OR = 1.52, 95% CI = 1.07–2.17, and P = 0.02).ConclusionsThis study demonstrates an association of rs11610206 polymorphism locus on chromosome 12q13 with risk for LOAD in Han Chinese.     

Association study: SLC6A18 gene and myocardial infarction

ObjectiveSLC6A18 (solute carrier family 6, member 18) acts as a specific transporter for neurotransmitters, amino acids and osmolytes such as betaine, taurine and creatine. The aim of the present study was to investigate the relationship between the human SLC6A18 gene and myocardial infarction (MI) in a Japanese population.MethodsUsing 5 single nucleotide polymorphisms in the SLC6A18 gene (rs7728646, rs4975625, rs12522796, rs4975623 and rs7447815) we performed a case-control study based on each SNP and haplotype in 289 MI patients and 223 controls.ResultsLogistic regression analysis revealed that the frequency of the CC + CG genotype of rs7447815 was significantly higher in all patients and the male MI patients than in controls (P = 0.005, P = 0.036, respectively). The frequency of the T-C haplotype (rs7728646–rs7447815) was significantly higher for the MI patients when compared with controls (P = 0.037).ConclusionsThese results suggest that SLC6A18 or neighboring genes are associated with increased susceptibility to MI.     

Gamma-glutamyl transferase level predicts the development of hypertension in Hong Kong Chinese

BackgroundPlasma activities of alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase, and γ-glutamyl transferase (GGT) are often increased in cardiometabolic diseases. We investigated if hypertension is associated with increased activities of these plasma markers.MethodsWe included 235 hypertensive and 708 normotensive subjects (mean age 47.3 ± 9.6 and 58.0 ± 10.2 years respectively) from the Hong Kong Cardiovascular Risk Factor Prevalence Study-2 (CRISPS-2) in 2000–2004 who had drank < 1/week. In the follow-up study in 2005–2008 (CRISPS-3), 126 out of the 708 subjects had developed hypertension.ResultsRaised plasma ALT (OR = 1.22 per SD of log-transformed level, P = 0.045) and GGT (OR = 1.38 per SD of log-transformed level, P = 0.001) levels were associated with hypertension at baseline in CRISPS-2 after adjusting for covariates. Among subjects not on anti-hypertensive medications, plasma ALP, ALT and GGT were related to blood pressure (P < 0.01). In subjects normotensive at CRISPS-2, plasma GGT, but not ALP, ALT and AST, was an independent predictor of new-onset hypertension at CRISPS-3 (OR = 1.38 per SD of log-transformed level, P = 0.020 and OR = 2.68 for 3rd tertile vs. 1st tertile, P = 0.004) after adjusting for covariates.ConclusionsAmong the 4 plasma markers, increased GGT activity is the strongest predictor for existing and new-onset hypertension in Hong Kong Chinese.