Genetic Variant ofKalirinGene Is Associated with Ischemic Stroke in a Chinese Han Population

Introduction.Ischemic stroke is a complex disorder resulting from the interplay of genetic and environmental factors. Previous studies showed that kalirin gene variations were associated with cardiovascular disease. However, the association between this gene and ischemic stroke was unknown. We performed this study to confirm if kalirin gene variation was associated with ischemic stroke.Methods.We enrolled 385 ischemic stroke patients and 362 controls from China. Three SNPs of kalirin gene were genotyped by means of ligase detection reaction-PCR method. Data was processed with SPSS and SHEsis platform.Results.SNP rs7620580 (dominant model: OR = 1.590,p= 0.002 and adjusted OR = 1.662,p= 0.014; additive model: OR = 1.490,p= 0.002 and adjusted OR = 1.636,p= 0.005; recessive model: OR = 2.686,p= 0.039) and SNP rs1708303 (dominant model: OR = 1.523,p= 0.007 and adjusted OR = 1.604,p= 0.028; additive model: OR = 1.438,p= 0.01 and adjusted OR = 1.476,p= 0.039) were associated with ischemic stroke. The GG genotype and G allele of SNP rs7620580 were associated with a risk for ischemic stroke with an adjusted OR of 3.195 and an OR of 1.446, respectively. Haplotype analysis revealed that A–T–G,G-T-A, and A-T-A haplotypes were associated with ischemic stroke.Conclusions.Our results provide evidence that kalirin gene variations were associated with ischemic stroke in the Chinese Han population.

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Association between PNPLA2 Gene Polymorphisms and the Risk of Diabetic Kidney Disease in a Chinese Han Population with Type 2 Diabetes

Journal of Diabetes Research ◽

10.1155/2020/5424701 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7

Author(s):

Hailing Zhao ◽

Haojun Zhang ◽

Yan Wang ◽

Tingting Zhao ◽

Meihua Yan ◽

...

Keyword(s):

Type 2 Diabetes ◽

Odds Ratio ◽

Diabetic Kidney Disease ◽

Adjusted Odds Ratio ◽

Additive Model ◽

Chinese Han Population ◽

Dominant Model ◽

Chinese Han ◽

Han Population

Diabetic kidney disease (DKD) is one of the most common complications of diabetes and the leading cause of end-stage renal disease. Here, we investigated the association of PNPLA2 gene variations with DKD susceptibility in a Chinese Han population. A total of 818 participants with type 2 diabetes were recruited in the case-control study, including 379 patients diagnosed with DKD. We observed that 2 tagSNPs, PNPLA2 rs28633403 (A>G) and rs1138714 (A>G), were associated with DKD (rs28633403: genotype, P=0.017; allele, P=0.015; rs1138714: genotype, P=0.029; allele, P=0.018). PNPLA2 rs1138693 (T>C), a missense SNP, showed no association with DKD (genotype, P=0.966; allele, P=0.845). Genetic model analysis revealed that minor allele G of PNPLA2 rs28633403 was a protective factor of DKD in a dominant model adjusted by confounders (AG+GG vs. AA: adjusted odds ratio (aOR), 0.619; 95% CI 0.447-0.857; P=0.004) and in an additive model (AG vs. AA: aOR, 0.633; 95% CI 0.447-0.895; P=0.010; GG vs. AA: aOR, 0.588; 95% CI 0.385-0.897; P=0.014). Minor allele G of PNPLA2 rs1138714 was associated with a higher risk of DKD in a dominant model adjusted by confounders (AG+GG vs. AA: adjusted odds ratio (aOR), 1.531; 95% CI 1.134-2.067; P=0.005) and in an additive model (AG vs. AA: aOR, 1.529; 95% CI 1.118-2.091; P=0.008). The combined effect of PNPLA2 rs28633403 AA+rs1138714 AG or GG genotype showed an association with DKD, adjusted by confounders (aOR, 2.194; 95% CI 1.378-3.492; P=0.001), which was considered statistically significant with a markedly increased risk of DKD after a Holm-Bonferroni correction for multiple tests (P<0.00125). Our results suggest that PNPLA2 rs28633403 and rs1138714 are significantly associated with the risk of DKD in a Chinese Han population with type 2 diabetes.

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Association between the ACYP2 Polymorphisms and IgAN Risk in the Chinese Han Population

Kidney & Blood Pressure Research ◽

10.1159/000501703 ◽

2019 ◽

Vol 44 (4) ◽

pp. 810-822

Author(s):

Gang Jin ◽

Yan Liang ◽

Xiaohui Yan ◽

Linping Zhang ◽

Zhenjiang Li ◽

...

Keyword(s):

Association Studies ◽

Immunoglobulin A ◽

Additive Model ◽

Recessive Model ◽

Chinese Han Population ◽

Nucleotide Polymorphisms ◽

Bonferroni Correction ◽

Chinese Han ◽

Han Population ◽

Increased Risk

Background/Aims: The association between ACYP2(Acylphosphatase 2) polymorphisms and immunoglobulin A nephropathy (IgAN) risk in the Chinese Han population remains unclear. We aimed to evaluate the association between ACYP2 polymorphisms and IgAN risk by performing a case-control study. Methods: Eleven ACYP2 single nucleotide polymorphisms (SNPs) from 416 IgAN patients and 495 healthy controls were genotyped using the Sequenom MassARRAY platform. Odds ratio (OR) and 95% confidence interval (CI) were calculated to evaluate the association of ACYP2 polymorphisms with IgAN risk. Results: We observed that rs843720 was significantly associated with an increased risk of IgAN (allele G: OR = 1.23, 95% CI: 1.01–1.49, p = 0.036; dominant model: OR = 1.55, 95% CI: 1.01–2.37, p =0.044; log-additive model: OR = 1.43, 95% CI: 1.04–1.95, p = 0.026) before Bonferroni correction. The SNP rs12615793 was also significantly associated with an increased IgAN risk in the recessive model (OR = 3.33, 95% CI: 1.05–10.51, p = 0.042) before Bonferroni correction. Conclusion: These findings suggested that polymorphisms (rs843720 and rs12615793) of ACYP2 may be pivotal in the development of IgAN. However, more functional and association studies with larger sample sizes should be performed to further validate our results in the future.

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Association studies of candidate single-nucleotide polymorphisms with Symptomatic Intracranial Atherosclerotic Stenosis in a Chinese Han population

10.21203/rs.2.15213/v1 ◽

2019 ◽

Author(s):

Fang Yu ◽

Xiaoqing Zhou ◽

Sian Zeng ◽

Xianjing Feng ◽

Zhibin Li ◽

...

Keyword(s):

Candidate Gene ◽

Association Studies ◽

Additive Model ◽

Genetic Models ◽

Chinese Han Population ◽

Dominant Model ◽

Chinese Han ◽

Han Population ◽

Intracranial Atherosclerotic Stenosis ◽

Atherosclerotic Stenosis

Abstract Background: Genetic factors underlying predisposition to Symptomatic Intracranial Atherosclerotic Stenosis (sICAS) remain unknown, the purpose of the present study was to identify genetic variants that confer susceptibility to sICAS in a Chinese Han population. Methods: The study population comprised of 379 Chinese individuals, including 193 patients with sICAS and 186 unrelated healthy controls. A total of 96 polymorphisms selected by genome-wide association or candidate-gene association studies of atherosclerosis and atherosclerotic diseases were examined in the present study with the use of Illumina VeraCode technology. Statistical analyses were performed with PLINK and SPSS software, and each genotype was assessed according to dominant, recessive, and additive genetic models. Results: Comparisons between subjects with sICAS and controls revealed that rs3798220 of the lipoprotein(a) gene (LPA) and rs9818870 of the muscle RAS oncogene homolog gene (MRAS) were significantly (P<0.0005, Bonferroni correction) associated with the prevalence of sICAS. Comparisons of genotypes in three genetic models (dominant, recessive and additive models) between groups showed that rs3798220 (LPA) was associated with sICAS in the dominant model (P=0.000005, OR=2.629, 95% CI=1.735-3.985) and additive model (P=0.000005, OR=2.293, 95% CI=1.605-3.276),while rs9818870 (MRAS) was associated with sICAS in the additive model (P=0.000464, OR=3.245, 95% CI=1.679-6.272). Furthermore, logistic regression analysis showed that the genotype distribution of rs3798220 (LPA) was significantly associated with sICAS, with its minor C allele elevating sICAS risk (P=0.00002, dominant model, OR=3.951, 95% CI=2.100-7.434 and P=0.000053, additive model, OR=2.916, 95% CI=1.736-4.899). While rs9818870 (MRAS) showed no such significance (P>0.0005). Conclusion: LPA rs3798220 might be susceptibility loci for sICAS in Chinese Han individuals. Keywords: Symptomatic Intracranial Atherosclerotic Stenosis; risk factors; candidate gene; SNP.

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Association of GTF2I, NFKB1, and TYK2 Regional Polymorphisms With Systemic Sclerosis in a Chinese Han Population

Frontiers in Immunology ◽

10.3389/fimmu.2021.640083 ◽

2021 ◽

Vol 12 ◽

Author(s):

Chenxi Liu ◽

Songxin Yan ◽

Haizhen Chen ◽

Ziyan Wu ◽

Liubing Li ◽

...

Keyword(s):

Systemic Sclerosis ◽

Genetic Model ◽

Additive Model ◽

Recessive Model ◽

Chinese Han Population ◽

Nucleotide Polymorphisms ◽

Chinese Han ◽

Association Analyses ◽

Han Population ◽

Increased Risk

ObjectivesSystemic sclerosis (SSc) is an uncommon autoimmune disease that varies with ethnicity. Single nucleotide polymorphisms (SNPs) in the GTFSI, NFKB1, and TYK2 genes have been reported to be associated with SSc in other populations and in individuals with various autoimmune diseases. This study aimed to investigate the association between these SNPs and susceptibility to SSc in a Chinese Han population.MethodA case-control study was performed in 343 patients with SSc and 694 ethnically matched healthy controls. SNPs in GTF2I, NFKB1, and TYK2 were genotyped using a Sequenom MassArray iPLEX system. Association analyses were performed using PLINK v1.90 software.ResultOur study demonstrated that the GTF2I rs117026326 T allele and the GTF2I rs73366469 C allele were strongly associated with patients with SSc (P = 6.97E-10 and P = 1.33E-08, respectively). Patients carrying the GTF2I rs117026326 TT genotype and the GTF2I rs73366469 CC genotype had a strongly increased risk of SSc (P = 6.25E-09 and P = 1.67E-08, respectively), and those carrying the NFKB1 rs1599961 AA genotype had a suggestively significantly increased risk of SSc (P = 0.014). Moreover, rs117026326 and rs73366469 were associated with SSc in different genetic models (additive model, dominant model, and recessive model) (P < 0.05) whereas rs1599961 was associated with SSc in the dominant genetic model but not in the addictive and recessive models (P = 0.0026). TYK2 rs2304256 was not significantly associated with SSc in this study.ConclusionGTF2I rs117026326 and rs73366469 SNPs were strongly associated with SSc in this Chinese Han population. NFKB1 rs1599961 showed a suggestive association with SSc, and no significant association was found between TYK2 rs2304256 and SSc in this Chinese Han population.

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Association of the gene polymorphisms of BMPR2, ACVRL1, SMAD9 and their interactions with the risk of essential hypertension in the Chinese Han population

Bioscience Reports ◽

10.1042/bsr20181217 ◽

2019 ◽

Vol 39 (1) ◽

Author(s):

Yunpeng Chen ◽

Chenxi Ye ◽

Jingwen Chen ◽

Dongming Lin ◽

Hao Wang ◽

...

Keyword(s):

Essential Hypertension ◽

Polymerase Chain Reaction Amplification ◽

White Blood Cells ◽

Recessive Model ◽

Chinese Han Population ◽

Dominant Model ◽

Nucleotide Polymorphisms ◽

Chinese Han ◽

Han Population ◽

Protein Receptor

Abstract Objective: Genetic factors are involved in the occurrence, development, and progression of essential hypertension (EH). To study the association between single nucleotide polymorphisms (SNPs) of the rs6435156 and rs1048829 loci of the bone morphogenetic protein receptor type 2 (BMPR2) gene, the rs121909287 and rs121909284 loci of the activin receptor-like kinase 1 (ACVRL1) gene, and the rs397514716 and rs121918359 loci of the mothers against decapentaplegic homolog 9 (SMAD9) gene with the risk of EH in the Chinese Han population. Materials and methods: A total of 460 EH patients and 460 healthy controls were recruited for the study. Genomic DNA of white blood cells was extracted, and the genotypes were analyzed by Sanger sequencing after polymerase chain reaction amplification. Multi-factor dimensionality reduction (MDR) was used to analyze the effect of gene–environment interactions on EH risk. Results: The risk of EH increased in the BMPR2 gene rs6435156 locus dominant model (adjusted odds ratio [OR] = 1.572, 95% confidence interval [CI]: 1.385–1.765, P<0.001) and recessive model (adjusted OR = 1.926, 95% CI: 1.693–2.067, P<0.001). The risk of EH increased in the rs1048829 recessive model (adjusted OR = 1.444, 95% CI: 1.142–1.696, P=0.003). The risk of EH increased in the recessive model of the ACVRL1 gene rs121909287 locus (adjusted OR = 1.403, 95% CI: 1.101–1.660, P=0.008). The risk of EH increased in the SMAD9 gene rs397514716 locus dominant model (adjusted OR = 1.370, 95% CI: 1.183–1.559, P<0.001) and recessive model (adjusted OR = 1.803, 95% CI: 1.470–1.983, P<0.001). The CG haplotype of the rs6435156 and rs1048829 loci of the BMPR2 gene, the CC haplotype of the ACVRL1 gene rs121909287 and rs121909284 loci, and the CC haplotype of the rs397514716 and rs121918359 loci of the SMAD9 gene were factors that protect against EH, whereas the TT haplotype of the rs6435156 and rs1048829 loci in the BMPR2 gene was a risk factor for EH. MDR analysis showed that the BMPR2 gene rs6435156 locus TT genotype carriers, the SMAD9 gene rs397514716 locus TT genotype carriers, and alcohol drinkers had the highest EH risk (OR = 4.523, 95% CI: 2.235–6.871, P<0.001). Conclusion: The SNPs of the rs6435156 and rs1048829 locus in the BMPR2 gene, the rs121909287 loci in the ACVRL1 gene, and the rs397514716 locus in the SMAD9 gene were associated with a risk of EH in Han Chinese.

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Association of Toll-Like Receptor 4 Gene Polymorphisms with Acute Aortic Dissection in a Chinese Han Population

BioMed Research International ◽

10.1155/2020/8306903 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Tan Li ◽

Xiaozheng Liu ◽

Hongxia Ning ◽

Xintong Li ◽

Jun Yang ◽

...

Keyword(s):

Aortic Dissection ◽

Acute Aortic Dissection ◽

Recessive Model ◽

Chinese Han Population ◽

Dominant Model ◽

Toll Like Receptor ◽

Chinese Han ◽

Toll Like Receptor 4 ◽

Han Population ◽

Increased Risk

Background. Inflammation may be involved in the pathogenesis of acute aortic dissection (AAD). Toll-like receptor 4 (TLR4) is known to play a critical role in regulating the immune and inflammatory processes. To date, the relationship between genetic variation of TLR4 and AAD is far from clear. The purpose of our study was to illustrate the relevance of TLR4 polymorphisms with the susceptibility to AAD. Methods. A total of 222 AAD patients and 222 controls were enrolled in this study. Frequency distributions of TLR4 polymorphisms (rs10759932 in the promoter and rs11536889 in the 3 ′ -untranslated region) were determined by the KASP method. Clinical parameters were acquired from subjects’ medical records, and serum TLR4 levels were collected from our previously published data. Results. We found that rs10759932 polymorphism was associated with a reduced risk of AAD in the overall population (CC vs. TT: OR = 0.393 , 95 % CI = 0.164 ‐ 0.939 , P = 0.036 ; recessive model: OR = 0.439 , 95 % CI = 0.196 ‐ 0.984 , P = 0.045 ) and subgroup analyses stratified by sex. The GC genotype and dominant model of rs11536889 conferred a significantly higher risk of AAD compared with GG genotype in female subjects (GC vs. GG: OR = 3.382 , 95 % CI = 1.051 ‐ 10.885 , P = 0.041 ; dominant model: OR = 3.043 , 95 % CI = 1.041 ‐ 8.900 , P = 0.042 ). In addition, a significant interaction between the rs11536889 recessive model and dyslipidemia was observed for an increased risk of AAD ( P interaction = 0.038 , OR = 15.229 ) after the adjustment for potential clinical covariates. We also used the false-positive report probability (FPRP) analysis to validate the significant results. Furthermore, rs11536889 polymorphism could affect the maximal aortic diameters of AAD ( P = 0.037 ), while AAD patients carrying CC genotype of rs10759932 showed lower serum TLR4 levels than TT genotype carriers ( P = 0.043 ). Conclusions. Our findings provide evidence for the association between TLR4 polymorphisms and AAD susceptibility in a Chinese Han population, which may have some implications for understanding the role of TLR4 in the pathophysiology of AAD.

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