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.     

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.     

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.     

Identification of pharmacogenetic predictors of lipid-lowering response to atorvastatin in Chilean subjects with hypercholesterolemia

BackgroundStatins are normally the first-line therapy for hypercholesterolemia (HC); however, the lipid-lowering response shows high interindividual variation. We investigated the effect of four polymorphisms in CYP3A4, CYP3A5 and ABCB1 genes on response to atorvastatin and CYP3A4 activity in Chilean subjects with HC.MethodsA total of 142 hypercholesterolemic individuals underwent atorvastatin therapy (10 mg/day/1 month). Serum lipid levels before and after treatment were measured. Genetic variants in CYP3A4 (? 290A>G, rs2740574), CYP3A5 (6986A>G, rs776746) and ABCB1 (2677G>A/T, rs2032582 and 3435C>T, rs1045642) were analyzed by PCR-RFLP. CYP3A4 enzyme activity in urine samples was assessed through determination of 6β-hydroxycortisol/cortisol free ratio (6βOHC/FC).ResultsAfter 4 weeks of therapy, a significant reduction in total cholesterol (TC) and LDL-c was observed (P < 0.001). The G allele for ? 290A>G polymorphism was related to higher percentage of variation in TC and LDL-c (P < 0.001). Moreover, same allele was associated with higher HDL-c variation (P = 0.017). In addition, CYP3A4 enzyme activity was lower in subjects carrying this polymorphism (P = 0.009). No differences were observed for CYP3A5 and ABCB1 variants.ConclusionOur results suggest that presence of G allele for ? 290A>G polymorphism determines a better response to atorvastatin, being also associated with lower CYP3A4 activity in vivo, causing an increased atorvastatin activity.     

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.     

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.     

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.     

Monocyte chemoattractant protein 1-2518 A/G polymorphism and susceptibility to type 2 diabetes in a Chinese population

BackgroundHyperglycemia could accelerate monocyte chemoattractant protein 1 (MCP-1) production in monocytes and vascular endothelial cells. Recently, a genetic polymorphism (–2518 A/G) located in MCP-1 gene promoter has been found that could influence the expression of MCP-1. A large cohort study of Caucasians reported that MCP-1 G–2518 gene variant was negatively correlated with the prevalence of insulin resistance and type 2 diabetes. However, it is unclear whether this polymorphism is associated with type 2 diabetes in Han Chinese.MethodsWe conducted a population-based case–control study of 416 type 2 diabetes cases and 416 controls.ResultsCompared with the wild genotype AA, MCP-1 G–2518 gene variant could significantly decrease the prevalence of type 2 diabetes in Han Chinese (adjusted OR = 0.49, 95% CI 0.32–0.77, P < 0.0001). The results of stratified analyses indicated that a decreased risk of type 2 diabetes related with variant genotypes was evident in younger participants (age ≤ 50) (adjusted OR = 0.35, 95% CI 0.20–0.61, P < 0.0001), and similar results were observed in males (adjusted OR = 0.37, 95% CI 0.21–0.66, P = 0.001) and urban participants (adjusted OR = 0.35, 95% CI 0.21–0.58, P < 0.0001). In addition, a statistically significant difference was observed between MCP-1–2518 A/G polymorphism and waist to hip ratio.ConclusionsOur present pilot study indicated that MCP-1 G–2518 gene variant could significantly decrease the risk of type 2 diabetes in a Chinese population.     

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.     

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 between the -2518G/A polymorphism in the monocyte chemoattractant protein-1 (MCP-1) gene and hypertension in Tunisian patients

ObjectivesMonocyte chemoattractant protein-1 (MCP-1:CCL2) has been demonstrated to be involved in the pathophysiology of atherosclerosis and hypertension. This study was aimed to investigate whether the single nucleotide polymorphism (SNP) at ?2518 of the MCP-1 gene promoter region is associated to hypertension in a sample of Tunisian population.Design and methodsA total of 290 Tunisian patients with hypertension and 390 normotensive controls were included in the study. The SNP of the MCP-1 gene was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis.ResultsA significant difference in genotype distribution and allele frequency was observed between patients and controls. Patients with hypertension had a frequency of 7.2% for the GG genotype, 35.2% for the AG genotype and 57.6% for the AA genotype. Normotensive subjects had a frequency of 3.6% for the GG genotype, 29.7% for the AG genotype and 66.7% for the AA genotype (χ² = 8.02, p = 0.01). The hypertension patient group showed a significant higher frequency of the G allele compared to the controls [0.24 vs. 0.18; OR (95%CI), 1.46 (1.11–1.91), p = 0.004]. The association between the ?2518 G/A polymorphism of MCP-1 gene and hypertension remained significant after adjustment for other well-established cardiovascular risk factors.ConclusionThe present study showed a significant and independent association between the ?2518G/A polymorphism of the MCP-1 gene (presence of G allele) and hypertension in the Tunisian 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.     

The association between transforming growth factor β3 polymorphisms and left ventricular structure in hypertensive subjects

BackgroundTransforming growth factor β (TGF-β) may be a crucial regulator of cardiac remodeling. We investigated the association between the TGF-β gene polymorphisms and left ventricular structure.MethodsA total of 658 hypertensive subjects were genotyped for the TGF-β1 T869C and TGF-β3 (rs3917187 and rs4252338) polymorphisms.ResultsTGF-β3 rs3917187 AA homozygotes had, while accounting for covariates, greater left ventricular end-systolic (LVESD, P = 0.004) and end-diastolic dimension (LVEDD, P = 0.007) than G allele carriers. Moreover, left ventricular mass index (LVMI) in AA genotype was 123.0 ± 3.1 g/m² significantly higher than that in AG (114.6 ± 1.6 g/m²) and GG (115.4 ± 2.1 g/m², P = 0.03) genotypes. In multivariate regression analysis, TGF-β3 rs3917187 genotype as an independent predictor had statistically significant effects on LVESD (β = 0.164, P = 0.002), LVEDD (β = 0.172, P = 0.003) and LVMI (β = 0.136, P = 0.016), respectively. In further analyses, we observed a significant interaction between the rs3917187 and alcohol intake in relation to LVESD (P_int = 0.04) and left ventricular fractional shortening (LVFSH, P_int = 0.012). However, no relationship could be found between left ventricular parameters and the T869C or the rs4252338.ConclusionThe present results demonstrated that the TGF-β3 rs3917187 polymorphism was associated with left ventricular structure, and had an interactive influence with alcohol on LVESD and LVFSH in hypertensive subjects.     

Single nucleotide polymorphism rs1333049 on chromosome 9p21.3 is associated with Alzheimer's disease in Han Chinese

BackgroundChromosome 9p21.3 polymorphism has been shown to affect susceptibility to Alzheimer's disease (AD) in Caucasians, while there are no studies on the association of chromosome 9p21.3 polymorphism with the risk of AD in Asians.MethodsThe study investigated 266 sporadic late-onset AD (LOAD) and 323 healthy controls matched for sex and age in a Han Chinese population. The common genetic variant (tagged by rs1333049, G/C) on chromosome 9p21.3 was genotyped using MALDI-TOF mass spectrometry.ResultsPatients with LOAD had higher frequencies of C allele (56.0% vs. 49.2%) compared with controls [odds ratio (OR) 1.31, 95% confidence interval (CI) 1.04–1.65, P = 0.02]. After stratification by APOE ε4-carrying status, the C allele of rs1333049 was only significantly associated with LOAD in non-APOE ε4 allele carriers (OR 1.47, 95% CI 1.09–1.98, P < 0.01). rs1333049 polymorphism was still strongly associated with LOAD [dominant model: OR 1.83, 95% CI 1.17–2.86, P < 0.01; additive model: OR 1.38, 95% CI 1.05–1.80, P = 0.02] after adjusting for the APOE ε4 carrier status and other vascular risk factors.ConclusionsThis study demonstrates an association of rs1333049 polymorphism locus on chromosome 9p21.3 with risk for LOAD in Han Chinese.     

Ubiquitin specific proteases USP24 and USP40 and ubiquitin thiolesterase UCHL1 polymorphisms have synergic effect on the risk of Parkinson's disease among Taiwanese

BackgroundImpaired ubiquitin–proteasome system function may contribute to the pathogenesis of Parkinson's disease (PD).MethodsWe conducted a case–control study in a cohort of 517 PD cases and 518 ethnically matched controls to investigate the association of ubiquitin specific proteases USP24 rs487230 C>T, USP40 rs1048603 C>T, and ubiquitin thiolesterase UCHL1 rs5030732 A>C polymorphisms with the risk of PD.ResultsNo significant difference in the genotype or allele distribution was found between PD and controls. After stratification by age, the genotype and allele frequencies of USP24 rs487230 are significantly different between PD and controls ≥ 60 years of age (P = 0.035 and 0.013, respectively). Multivariable logistic regression with adjusting for onset age and sex showed that, in a dominant model, USP24 T-carrying genotype was associated with risk reduction in developing PD in individuals ≥ 60 years of age (OR = 0.61; 95% CI = 0.41–0.90, P = 0.010). This is also true for T allele (OR = 0.64; 95% CI = 0.44–0.91, P = 0.023). When examining the interaction between genes on PD risk without age stratification, the protective effect of USP24 CT/TT genotype on PD risks was strengthened by the USP40 T-carrying genotype (OR = 0.42; 95% CI = 0.22–0.81, P = 0.009) and UCHL1 C-carrying genotype (OR = 0.67; 95% CI = 0.47–0.97, P = 0.032).ConclusionsOur results suggest that USP24 alone plays a role in PD susceptibility among Taiwanese people ≥ 60 years of age, or acting synergistically with USP40 and UCHL1 in the total subjects.     

Plasma concentrations but not serum concentrations of brain-derived neurotrophic factor are related to pro-inflammatory cytokines in patients undergoing major abdominal surgery

ObjectivesTo investigate peripheral brain-derived neurotrophic factor (BDNF) concentrations in the perioperative period, their relationship with transforming growth factor-β1 (TGF-β1 tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-6 genetics.Design and methodsProspective, observational study. BDNF, TGF-β1, IL-6 and TNF-α were analysed at baseline (T0), 5 h (T1), 24 h (T2) and 5 days (T3) after surgery, in 21 patients. The IL-6 ? 174 G/C polymorphism was genotyped.ResultsSerum BDNF concentrations decreased (P = 0.048), correlated with TGF-β1 (r = 0.610 at T1, r = 0.493 at T2, r = 0.554 at T3). Plasma BDNF concentrations raised (P = 0.049), correlated with IL-6 and TNF-α at T1 (r = 0.495 and r = 0.441, respectively). BDNF response was predictable from TNF-α and IL-6 concentrations and the IL-6 ? 174 G/C genotype.ConclusionSerum and plasma BDNF concentrations could relate to platelet activation and inflammatory response, respectively. IL-6 genetics played a role in the BDNF acute response.     

Synergistic effects of the polymorphisms in the PAI-1 and IL-6 genes with smoking in determining their associated risk with coronary artery disease

ObjectivesTo assess the relationship between IL-6 and PAI-1 polymorphisms and coronary artery disease (CAD) and to observe the interactions between these polymorphic variants and smoking in the CAD risk.Design and methodThe study population consisted of 178 patients with angiographically documented CAD and 202 blood donors. The analyses of genetic polymorphisms were performed using the PCR-RFLP method.ResultsThe frequency of PAI-1 5G allele was higher in the entire CAD group than in control group (p = 0.04, OR = 1.35). Also the 5G allele carriers (4G5G + 5G5G) were more frequent in patients than in controls (p = 0.03, OR = 1.93). The number of women carrying 5G allele was again significantly higher among patients (OR = 10.95 p = 0.0075). The IL-6 C allele frequency was higher only in the CAD male subgroup (p = 0.035, OR = 1.44). We found synergistic and cumulative effects between specific genotype patterns and smoking in determining the risk of CAD, especially between PAI-1(4G5G + 5G5G)+IL-6(CC) and smoking (SIM = 4.18 and p = 0.0005, OR = 9.20, respectively).ConclusionsThere are synergistic and cumulative effects of 5G allele of PAI-1 polymorphism and C allele of IL-6 polymorphism with smoking in determining their associated risk with CAD.     

Neuropeptide Y polymorphisms and ischemic stroke in Chinese population

BackgroundStroke is the second most common cause of death in developed countries and a major cause of adult disability and mortality worldwide. New data strongly suggest that neuropeptide Y (NPY) may be a candidate gene for ischemic stroke.MethodsWe investigated 450 ischemic stroke patients and 423 healthy controls matched for sex and age in a Han Chinese population. Three functional polymorphisms (? 883TGins/del, ? 602G/T and ? 399 T/C) located in NPY gene promoter were genotyped using DNA sequencing methods.ResultsOf 3 NPY polymorphisms investigated in our study, the ? 399CC genotype (OR: 1.699, 95% CI: 1.124–2.567, P = 0.011) and the ? 399C allele (OR: 1.254, 95% CI: 1.031–1.524, P = 0.023) were more frequent among ischemic stroke patients than in controls, especially in the small vessel disease (SVD) subtype patients. The similar results were observed in multivariable logistic regression analysis. Haplotype analysis revealed that the ? 883ins/?399C haplotype was a risk marker for ischemic stroke (P = 0.008).ConclusionsThe C allele of ? 399 T/C polymorphism in the promoter regions of NPY is an independent risk factor for ischemic stroke, suggesting that NYP system may involve in the mechanisms of stroke pathology.     

Relationship between circulating cytokine levels and physical or psychological functioning in patients with advanced cancer

ObjectiveTo investigate the relation between functional impairments of cancer patients and circulating cytokines using a multiplex technique.Design and methods50 patients with cancer were assessed using the quality of life (QOL) questionnaire. 27 plasma cytokine levels were determined by using the Bio-Plex array system. The relation to QOL scores was assessed using Chi-square test for categorical variables and univariate linear regression analysis for cytokine levels.ResultsMultivariate analysis showed that interleukin-6 (IL-6) level is a significant independent determinant of physical (β = ? 0.238, P = 0.0126) and cognitive functioning (β = ? 0.462, P = 0.0006) and that vascular endothelial growth factor (VEGF) level is a significant independent determinant of emotional functioning (β = ? 0.414, P = 0.039).ConclusionThis study, in which 27 cytokines are simultaneously tested with cutting edge technology, demonstrates that plasma IL-6 and VEGF are significant independent determinants of functional impairments in patients with cancer.     

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.