Disease In Chinese Han Population Research Articles

Exploring the interaction among EPHX1, GSTP1, SERPINE2, and TGFB1 contributing to the quantitative traits of chronic obstructive pulmonary disease in Chinese Han population.

BackgroundCurrently, the majority of genetic association studies on chronic obstructive pulmonary disease (COPD) risk focused on identifying the individual effects of single nucleotide polymorphisms (SNPs) as well as their interaction effects on the disease. However, conventional genetic studies often use binary disease status as the primary phenotype, but for COPD, many quantitative traits have the potential correlation with the disease status and closely reflect pathological changes.MethodHere, we genotyped 44 SNPs from four genes (EPHX1, GSTP1, SERPINE2, and TGFB1) in 310 patients and 203 controls which belonged to the Chinese Han population to test the two-way and three-way genetic interactions with COPD-related quantitative traits using recently developed generalized multifactor dimensionality reduction (GMDR) and quantitative multifactor dimensionality reduction (QMDR) algorithms.ResultsBased on the 310 patients and the whole samples of 513 subjects, the best gene-gene interactions models were detected for four lung-function-related quantitative traits. For the forced expiratory volume in 1 s (FEV1), the best interaction was seen from EPHX1, SERPINE2, and GSTP1. For FEV1%pre, the forced vital capacity (FVC), and FEV1/FVC, the best interactions were seen from SERPINE2 and TGFB1.ConclusionThe results of this study provide further evidence for the genotype combinations at risk of developing COPD in Chinese Han population and improve the understanding on the genetic etiology of COPD and COPD-related quantitative traits.Electronic supplementary materialThe online version of this article (doi:10.1186/s40246-016-0076-0) contains supplementary material, which is available to authorized users.

NPR-C gene polymorphism is associated with increased susceptibility to coronary artery disease in Chinese Han population: a multicenter study.

To find a new locus that confers significant susceptibility to CAD in Chinese Han population, a genome-wide association study in 200 “extreme individuals” from a Shandong cohort and a pathway-based candidate gene study from a Shanghai cohort (293 CAD/293 controls) were simultaneously performed. Amongst them, 13 SNPs associated with CAD were selected to conduct validation and replication studies in additional 3363 CAD patients and 3148 controls. A novel locus rs700926 in natriuretic peptide receptor C (NPR-C) was identified in Shandong and Hubei cohorts. Then rs700926 and other nine tag SNPs were genotyped in four geographically different populations (Shandong, Shaanxi, Hubei and Sichuan cohorts), and 6 SNPs (rs700926, rs1833529, rs2270915, rs17541471, rs3792758 and rs696831) showed stronger association with CAD, regardless of single or combined analysis. We further genotyped rs2270915 and 10 additional tag SNPs in a central China cohort and identified rs12697273 and rs10066436 as the loci associated with CAD. All these positive associations remained significant after adjustment for traditional risk factors of CAD. NPR-C gene SNPs significantly contribute to CAD susceptibility in the Chinese Han population.

Association of single nucleotide polymorphism rs2076185 in chromosome 6P24.1 with premature coronary artery diseases in Chinese Han population.

ObjectivesTo study the association of single nucleotide polymorphism (SNP) rs2076185 in chromosome 6p24.1 with the premature coronary artery diseases (PCAD) in Chinese Han population.MethodsA total of 1382 patients were divided into the PCAD group and the control group based on their coronary arteriography (CAG) results. Their SNP rs2076185 were analyzed by the mass-spectrometry. Their allele and genotype frequency in Hardy-Weinberg equilibrium were calculated for assessment. Logistic regression was employed to remove confounding factors and correlate SNP rs2076185 with PCAD.ResultsThe allele and genotype frequencies of the control group were in Hardy-Weinberg equilibrium (P > 0.05). The frequencies of allele G of rs2076185 were 54.2% in the PCAD group and 49.5% in the control group. The difference was significant (P = 0.042). The genotype distribution of rs2076185 of the two groups was also significantly different. The univariate analysis showed that the rs2076185 polymorphisms were associated with the PCAD only in the additive model (OR: 0.828, 95% CI: 0.711−0.964, P = 0.014), and in the dominant model (OR: 0.753, 95% CI: 0.591−0.958, P = 0.021). After removing the confounding variables, the rs2076185 polymorphisms was associated with PCAD in the additive model (OR: 0.775, 95% CI: 0.648−0.928, P = 0.005), in the dominant model (OR: 0.698, 95% CI: 0.527−0.925, P = 0.012), and in the recessive model (OR: 0.804, 95% CI: 0.538−0.983, P = 0.038).ConclusionAllele G of rs2076185 reduces the PCAD risks in Chinese Han population, therefore it could be a coronary artery diseases protective factor in Chinese Han population.

Association Study of Single-Nucleotide Polymorphisms on Chromosome 1p13, 1p32, 9p21 and 19p13 with Cardiovascular Diseases in Chinese Han Population: A Case-Control Study

Objectives: Previous research discovered single nucleotide polymorphism (rs2383206 and rs2383207) on chromosome 9p21 that is associated with coronary heart disease in a Chinese population. However, few data are available on the association of other single nucleotide polymorphism with cardiovascular disease in a Chinese population. This study aimed to determine whether the single nucleotide polymorphisms on chromosome 1p13, 1p32, 9p21 and 19p13 were associated with coronary artery disease in a Chinese population. Methods: We conducted a case-control study. Cases were coronary artery disease (n=670) between 2010 and 2015. Controls (n=1340) were randomly selected and frequency matched to cases on age and gender. All of the participants were selected to study 18 single nucleotides using allele-specific real-time polymerase chain reaction method. Results: Four single nucleotides in 9p21, two single nucleotides in 1p13 and one single nucleotide in 1p32 were associated with cardiovascular disease risk in Chinese population (Global P value for multiple logistic regression, <0.0001, respectively). rs10757274 showing the strongest association with cardiovascular disease. GG carriers of four SNPs (rs10757274, rs2383206, rs10757278 and rs1333049) in 9p21 had higher risk (Odds ratio=1.40, 95% Confidence interval: 1.10-1.79; Odds ratio=1.33, 95% Confidence interval: 1.04-1.69; Odds ratio=1.35, 95% Confidence interval: 1.07-1.72; Odds ratio=1.34, 95% Confidence interval: 1.06-1.71). Conclusion: rs10757274, rs2383206, rs10757278 in 9p21, rs562556 in 1p32, and rs646776 in 1p13 may serve as a novel genetic marker for the risk of significant cardiovascular disease in Chinese Han population.

Analysis of LRRK2, SNCA, and ITGA8 Gene Variants with Sporadic Parkinson's Disease Susceptibility in Chinese Han Population.

Background. Parkinson's disease (PD) is an age-related neurodegenerative disease affected by multiple genetic and environmental factors. We performed a case-control study on candidate gene to scrutinize whether genetic variants in LRRK2, SNCA, and ITGA8 genes could be associated with sporadic PD in Chinese Han population. Methods. Five single-nucleotide polymorphisms (SNPs) of LRRK2 (rs1491942), SNCA (rs2301134, rs2301135, and rs356221), and ITGA8 (rs7077361) were selected and genotyped among 583 unrelated PD patients and 558 healthy controls. Results. Rs1491942 of LRRK2 gene had a significantly higher genotype frequency (P = 3.543E − 09) and allelic G/C frequencies (P = 2.601E − 10) in PD patients than controls. Rs2301135 of SNCA gene also showed an obvious difference in genotype frequency (P = 4.394E − 07) and allelic G/C frequencies (P = 9.116E − 13) between PD patients and controls. SNPs rs2301134 and rs356221 of SNCA gene and rs7077361 of ITGA8 gene lacked the significant association with the susceptibility of PD in Chinese Han population. Conclusions. Our study firstly expresses that rs1491942 of LRRK2 and rs2301135 of SNCA gene are substantially associated with sporadic Parkinson's disease in Chinese Han population.

GW26-e4457 Associations among genetic variants in ccl17, serum CCL17 levels, and coronary artery disease in Chinese Han population

Our previous study has indicated that serum chemokine ligand 17 (CCL17) levels are associated with coronary artery disease (CAD) and atherosclerosis severity. This study is to further determine the relationship among genetic variants in ccl17 , serum CCL17 levels, and CAD in Chinese Han population

GW26-e2364 Flotillin-2 Gene is Associated With Coronary Artery Disease in Chinese Han Population

In human, vesicular endocytosis is an efficient way of dietary cholesterol absorption. Flotillins proteins included Flotillin-1, Flotillin-2 are considered to be the components of lipid rafts and are commonly used as marker proteins for lipid microdomains. Therefore, we investigated the association

Meta-analysis of the Association of Prol2Ala Polymorphism of Peroxisome Proliferator Activated Receptor Gamma Gene with Diabetic Kidney Disease in Chinese Han Population

Meta-analysis of the Association of Prol2Ala Polymorphism of Peroxisome Proliferator Activated Receptor Gamma Gene with Diabetic Kidney Disease in Chinese Han Population

Genetic analysis of P387L mutation in SLC18A2 gene in sporadic Parkinson's disease in Chinese Han population.

To investigate whether the mutation of P387L in SLC18A2 gene is a cause for sporadic Parkinson's disease (PD) in Chinese Han population. A total of 931 subjects (455 sporadic PD patients and 476 healthy controls) were enrolled in our study. SLC18A2 P387L was genotyped by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS) and the results were verified by Sanger sequencing. Furthermore, a case-control study was used to investigate the relationship between the mutation and sporadic PD. There was no mutation in any of the 931 individuals. The P387L mutation in SLC18A2 gene is rare in Chinese Han population, and P387L might not be a cause for Chinese sporadic PD. However, the role of this mutation in PD needs to be further verified through replication studies with large number of subjects and different population.

Association of TLR9 polymorphisms with sporadic Parkinson's disease in Chinese Han population

Previous studies have acknowledged that inflammatory reaction has implicated in Parkinson's disease (PD) pathogenesis nowadays. Toll-like receptors (TLRs), as key players in the inflammatory reaction, play a pivotal role in the PD pathogenesis and accumulating evidences have shown that TLRs are increased in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of PD. Therefore, the present study aimed to identify the role of the polymorphisms of rs187084 and rs352140 in TLR9 gene with PD. The genotypes were detected by polymerase chain reaction and restriction fragment length polymorphism analysis in 380 PD patients and 380 healthy matched individuals in Chinese Han population. For rs352140, our data revealed a significant difference in allele distribution in female PD group and its healthy matched control (P = 0.040). Moreover, rs352140 T allele carriers of female group were associated with a reduced risk of PD (TT + TC vs. CC, P = 0.018). However, no significant differences in genotype and allele distribution were found between the age and gender subgroups for rs187084. Therefore, our studies indicate that the rs352140 gene polymorphism may be associated with the susceptibility of female PD in Chinese Han population.

Association study of genetic variants at newly identified lipid gene TRIB1 with coronary heart disease in Chinese Han population.

BackgroundRecent genome-wide association studies (GWAS) have identified the variants near TRIB1 gene affecting blood lipid levels. However, the association between the reported variants and risk of coronary heart disease (CHD) was not confirmed.MethodsWe conducted two independent case–control studies. The first study consisted of 300 CHD patients and 300 controls and the second study had 1,332 CHD patients and 2,811 controls. The genotypes of two variants rs3201475 and rs17321515 in TRIB1 were determined by TaqMan assay. The dual-luciferase reporter assay was performed for evaluating the function of the SNP rs3201475.ResultsThe statistical analysis indicated that single nucleotide polymorphism (SNP) rs17321515 was replicated to be associated with triglyceride (TG) level, which was also significantly associated with CHD risk when using the stratified analysis after adjusting for conventional risk factors. Compared with GG genotype, AA carriers of SNP rs17321515 had higher risk in males (odds ratio (OR) = 1.28, 95 %CI = 1.01–1.61; P = 0.03) and smokers (OR = 1.41, 95%CI = 1.09–1.88; P = 0.01). We did not find significantly association between genotypes of rs3201475 and CHD risk. In addition, no significant difference was found in the luciferase activity assay of SNP rs3201475.ConclusionsOur findings indicated that SNP rs17321515 is significantly associated with plasma TG level and the increasing risk of CHD among males and smokers in Chinese, whereas there is no positive association between SNP rs3201475 and CHD risk. Smoking could modify the effects of TRIB1 on CHD risk.

Foxp3 gene polymorphisms and haplotypes associate with susceptibility of Graves' disease in Chinese Han population.

Foxp3 plays important roles in the pathogenesis of autoimmune diseases. To investigate the association between Foxp3 gene polymorphisms and the susceptibility to Graves' disease (GD) in Chinese Han population, four single nucleotide polymorphisms (SNPs) including -2383, -3279, -3499 in the promoter and IVS9+459 in the intron were genotyped. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 308 GD patients and 306 healthy controls. The relative expression level of Foxp3 gene was measured by qRT-PCR. The frequencies of AA/CA genotype of -3279 and CC genotype of IVS9+459 were significantly higher in GD patients than healthy controls. The AA/CA genotype of -3279 in female GD patients was more frequent than the male. For -3279, GD patients with higher TSH level or/and lower TRAb level were more frequent to carry A allele. We further analyzed the haplotypes of three SNPs and found that the haplotype CCA played a protective role in the susceptibility to GD. In contrast, the CAA and TCA haplotypes were associated with an increased susceptibility to GD. In addition, the mutation from C to A at the position of -3279 reduced the relative luciferase activity of Foxp3 promoter and decreased the expression of Foxp3 in GD patients. Our findings indicated that Foxp3 functional polymorphisms and haplotypes in promoter were associated with the susceptibility to GD in Chinese Han population.

Risk-Association of DNMT1 Gene Polymorphisms with Coronary Artery Disease in Chinese Han Population.

Recently, a significant epigenetic component in the pathogenesis of Coronary Artery Disease (CAD) has been realized. Here, we evaluated the possible association of candidate Single Nucleotide Polymorphisms (SNPs) in the epigenetic-regulatory gene, DNA methyltransferase 1 (DNMT1), with CAD in Chinese Han population. Five tag SNPs (rs16999593, rs2336691, rs2228611, rs4804494, rs7253062) were analyzed by High Resolution Melt (HRM) method in 476 CAD patients and 478 controls. Overall, there were significant differences in the genotype and allele distributions of rs2228611 and rs2336691, between patients and controls. The minor A allele of rs2228611 was associated with a lower risk of CAD (p = 0.034); modest effect in the additive analysis but also marginal significance was found in the recessive model [ORadditive = 0.404 (0.184, 0.884), p = 0.023 and ORrecessive = 0.452 (0.213, 0.963), p = 0.040] after adjusting for confounders. While the rs2336691 A allele were associated with a higher risk of developing CAD (p = 0.037); borderline significant association in both additive and dominant models [ORadditive = 1.632 (1.030, 2.583), p = 0.037 and ORdominant = 1.599 (1.020, 2.507), p = 0.040]. In conclusion, these data provide the first evidence that occurrence of CAD may be moderated by genetic variation in the gene involved in the epigenetic machinery.

GW25-e2291 A Novel Haplotype in the GOSR2 Gene is Associated With Coronary Artery Disease in Chinese Han population

GW25-e2291 A Novel Haplotype in the GOSR2 Gene is Associated With Coronary Artery Disease in Chinese Han population

Association study of TREM2 polymorphism rs75932628 with late-onset Alzheimer’s disease in Chinese Han population

Objective:We conducted a case–control study to investigate whether TREM2 polymorphism (rs75932628-T) was associated with late onset Alzheimer’s disease in Chinese Southern Han population.Methods:PCR-restriction fragment length polymorphism assay was performed to genotype rs75932628 in 279 cases with late onset Alzheimer’s diseases patients and 346 control subjects in Shanghai and Nanjing.Results:There was no rs75932628-T variant detected in our sample. However, APOEϵ4 was shown closely associated with the risk of Alzheimer’s disease (Chi-square = 60·288, P = 0·000).Conclusion:Our study suggested that TREM2 (rs75932628-T) was rare in Chinese Han population. Further association studies with large samples are needed to further study the association of TREM2 with late-onset Alzheimer’s disease.

Association analysis between MTHFR genetic polymorphisms and the risk of congenital heart diseases in Chinese Han population

Congenital heart diseases (CHD) are common birth defects in the world. The methylenetetrahydrofolate reductase (MTHFR) gene is one of the most important candidate genes for the development of CHD. This case-control study aimed to evaluate the effect of MTHFR c.382A>G and c.1129C>T genetic polymorphisms as risk factors for the development of CHD. A total of 230 CHD patients and 237 non-CHD controls were included in the present study. The genotyping of MTHFR c.382A>G and c.1129C>T genetic polymorphisms were detected by the polymerase chain reaction-restriction fragment length polymorphism and created restriction site-polymerase chain reaction methods, respectively. The alleles/genotypes distribution from these two genetic polymorphisms were statistically associated with the increased risk of CHD (for c.382A>G, GG versus AA: odds ratio (OR) = 2.39, 95% confidence interval (CI), 1.27 to 4.52, P = 0.006; for c.1129C>T, TT versus CC: OR = 2.73, 95% CI, 1.33 to 5.62, P = 0.005). The allele G and genotype GG of c.382A>G and allele T and genotype TT of c.1129C>T genetic polymorphisms might contribute to CHD susceptibility. These preliminary findings indicate that these two MTHFR genetic polymorphisms are related with the risk of CHD in Chinese Han population, and might be potentially utilized as molecular markers.

A Complex Association of ABCA7 Genotypes With Sporadic Alzheimer Disease in Chinese Han Population

Recently, a large genome-wide association study has revealed that polymorphism of alleles and genotypes in rs3,764,650 within ABCA7 gene is associated with Alzheimer disease in whites. We conducted a case-control study to investigate whether these susceptible genetic variants are risk factors for sporadic Alzheimer disease (SAD) in Chinese Han population. A total of 633 participants consisting of 350 SAD and 283 nondemented elderly controls matched for sex and age were recruited and genetic variants in ABCA7 (rs3,764,650) were genotyped using DNA sequencing. On the basis of allele and genotype frequencies in both groups, we found a significant association (P=0.004) between ABCA7 genotypes and SAD in Chinese Han population, and the results were influenced by age and ApoEε4 status. ApoEε4-carrier and aging are linked to enhancing ABCA7 risk-associated SAD. However, the prevalence of the minor allele G in rs3,764,650 within ABCA7 showed no significant difference between the 2 groups in this study. ABCA7 (rs3,764,650) was associated with SAD in the Chinese population, with both ApoEε4-carrier and aging being factors enhancing its risk.

Association of interleukin-4 genetic polymorphisms with sporadic Alzheimer's disease in Chinese Han population

Cytokine interleukin-4 (IL-4) is thought to play a role in the pathogenesis of Alzheimer's disease (AD). This study aimed to evaluate the potential association between single nucleotide polymorphisms (SNP) of IL-4 gene and AD susceptibility. This case-control study was conducted in Chinese Han populations consisting of 203 AD patients and 205 controls. Three common SNPs of IL-4 gene, including −590C>T (rs2243250), −33C>T (rs2070874), and −1098T>G (rs2243248), were determined by the polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) and verified using DNA sequencing methods. Our data show that −590C and −1098G alleles of IL-4 were more common in AD patients (30.5% vs 22.2% p=0.007; 14.3% vs 3.4% p<0.0001) and significantly associated with elevated risk for AD (OR=1.51 95% CI 1.05–2.23; OR=4.78 95% CI 2.37–7.67). Haplotype analysis revealed five common haplotypes CCG (OR=4.41), CCT (OR=1.22), TTT (OR=1.02), CTT (OR=0.7), and TCT (OR=0.14), from highest to lowest risk for AD. None of the associations appeared to be modified by APOE ɛ4 genetic variant. Bioinformatic analysis shows that −590C>T and −1098T>G have a linkage disequilibrium (LD) with multiple potentially functional SNPs inside IL-4 gene. Our findings indicate that the −590C and −1098G alleles located in the promoter of IL-4 may increase the susceptibility to AD among the Han Chinese and might be used as molecular markers for AD risk evaluation.

The Association between theLPAGene Polymorphism and Coronary Artery Disease in Chinese Han Population

Lp(a) has been well known as an independent risk factor for coronary artery disease (CAD). The LPA gene, as it encodes apo(a) of the Lp(a) lipoprotein particle, was associated with increased risk of CAD. The purpose of this study was to analyze the relationship between the polymorphisms of LPA gene and CAD in Chinese Han population. Five SNPs (rs1367211, rs3127596, rs6415085, rs9347438, and rs9364559) in the LPA gene were genotyped using Sequenom MassARRAY time-of-flight mass spectrometer (TOF) in 560 CAD patients as case group and 531 non-CAD subjects as control group. The numbers of these two groups were from Chinese Han ancestry. The results showed that allele (P = 0.046) and genotype (P = 0.026) of rs9364559 in the LPA gene was associated with CAD. The frequency of rs9364559 minor allele (G) in case group was obviously higher than that in control group. Results of haplotype analysis showed that 4 haplotypes which contained rs9364559-G were associated with increased risk of CAD in this population. This study explored rs9364559 in the LPA gene may be associated with the pathogenesis of CAD; and the risk of CAD might be higher in the population carrying 4 haplotypes of different blocks in the LPA gene.

Association of MYO9B gene polymorphisms with inflammatory bowel disease in Chinese Han population.

To explore the association of MYO9B gene polymorphisms with clinical phenotypes and intestinal permeability of individuals with inflammatory bowel disease (IBD) in China. A total of 442 IBD patients and 402 healthy volunteers were genotyped for two single nucleotides (rs962917 and rs1545620) using the ligase detection reaction and polymerase chain reaction. Allelic and genotype frequency analyses were performed for the two groups. Intestinal permeability was evaluated using lactulose (L) and mannitol (M) excretion. The association of MYO9B gene polymorphisms with intestinal permeability between the normal and high intestinal permeability groups was analyzed. Overall, there was no significant difference in the genotypic and allelic frequencies of MYO9B between IBD patients and controls. Although no association was found with ulcerative colitis in the comparison between the subgroups, the frequencies of rs962917 and rs1545620 were different in the Crohn's disease (CD) subgroup with ileocolitis (CC vs CT and TT, P = 0.014; and AA vs AC and CC, P = 0.022, respectively). rs1545620 variants appear to be the genetic susceptibility factor for perianal disease in CD patients (AA vs AC CC, P = 0.029). In addition, the L/M ratio was significantly higher in IBD patients than in controls (0.065 ± 0.013 vs 0.020 ± 0.002, P = 0.02), but no association was found between the MYO9B gene and the L/M ratio in IBD patients. MYO9B gene polymorphisms may influence the sub-phenotypic expression of CD in China. No association between these MYO9B polymorphisms and intestinal permeability in IBD patients was found.