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1.
Association of VEGF Gene Polymorphisms with Susceptibility to Diabetic Retinopathy: A Systematic Review and Meta-Analysis.
Yang, Q, Zhang, Y, Zhang, X, Li, X, Liu, J
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2020;(5):264-279
Abstract
The associations between vascular endothelial growth factor (VEGF) gene polymorphisms and risk of type 2 diabetic retinopathy (DR) - proliferative diabetic retinopathy (PDR), and nonproliferative diabetic retinopathy (NPDR) - remain unclear. A systematic search and meta-analysis using odds ratio (OR) with 95% confidence interval (CI) was performed to evaluate the association. Our study concluded 26 studies containing 10 single nucleotide polymorphisms (SNPs). In Asian populations, rs3025039 polymorphism was associated with DR risk, while in overall populations and Caucasians, the DR risk was increased by association with rs2010963. There was a significant association between rs25648 and rs833061 and DR risk in Caucasians. DR risks were found to be significantly associated between rs3025021, rs13207351, and rs2146323 in either overall populations, Caucasians or Asians. Besides, in overall and Asian populations, rs699947 and rs3025039 were associated with PDR risk. rs1570360, rs3025039, and rs833061 played a key role in PDR etiology in Caucasians. rs2010963 was associated with increased risk of PDR in overall populations. A significant association between rs699947, rs3025039, and rs833061 and NPDR risk in overall populations and Asians was found. A significant association was observed between rs2010963 and increased NPDR risk in overall and Caucasian populations. This study provides a new insight into the parthenogenesis of diabetic retinopathy. Targeting VEGF SNPs may be a potential of therapeutic approach for the treatment of DR, PDR, and NPDR.
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The association of the PCSK9 rs562556 polymorphism with serum lipids level: a meta-analysis.
Chuan, J, Qian, Z, Zhang, Y, Tong, R, Peng, M
Lipids in health and disease. 2019;(1):105
Abstract
BACKGROUND Studies had investigated the associations between proprotein convertase subtilisin/kexin type 9 SNP rs562556 and serum lipids levels and response to statin treatment, however, the results remained inconclusive. We conducted this meta-analysis to elucidate the relationship of rs562556 and serum lipids levels. METHODS All eligible studies met the inclusion criteria were retrieved from multiple databases. Relative data were extracted from each study. Review Manager (version 5.3.5) and STATA 12.0 software was used to perform this meta-analysis. Pooled standardized mean difference (SMD) with 95% CI was employed to evaluate the association of rs562556 with serum lipids levels. RESULTS A total of 7 eligible articles involving 4742 subjects were included in the final meta-analysis. The results revealed that the G carriers had lower levels of total cholesterol (SMD: 0.14, 95% Cl: 0.06-0.23, P = 0.001) and LDL-C(SMD: 0.13, 95% Cl: -0.55-0.22,P = 0.002) than the non-carriers. The statistical results also illustrated that the G carriers had lower relative risk (SMD: 1.38, 95% Cl: 1.02-1.85, P = 0.003) than the non-carriers. CONCLUSIONS The results of the current meta-analysis for the first time indicated the relevance of rs562556 and lower serum cholesterol levels.
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Effect of CYP4F2, VKORC1, and CYP2C9 in Influencing Coumarin Dose: A Single-Patient Data Meta-Analysis in More Than 15,000 Individuals.
Danese, E, Raimondi, S, Montagnana, M, Tagetti, A, Langaee, T, Borgiani, P, Ciccacci, C, Carcas, AJ, Borobia, AM, Tong, HY, et al
Clinical pharmacology and therapeutics. 2019;(6):1477-1491
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Abstract
The cytochrome P450 (CYP)4F2 gene is known to influence mean coumarin dose. The aim of the present study was to undertake a meta-analysis at the individual patients level to capture the possible effect of ethnicity, gene-gene interaction, or other drugs on the association and to verify if inclusion of CYP4F2*3 variant into dosing algorithms improves the prediction of mean coumarin dose. We asked the authors of our previous meta-analysis (30 articles) and of 38 new articles retrieved by a systematic review to send us individual patients' data. The final collection consists of 15,754 patients split into a derivation and validation cohort. The CYP4F2*3 polymorphism was consistently associated with an increase in mean coumarin dose (+9% (95% confidence interval (CI) 7-10%), with a higher effect in women, in patients taking acenocoumarol, and in white patients. The inclusion of the CYP4F2*3 in dosing algorithms slightly improved the prediction of stable coumarin dose. New pharmacogenetic equations potentially useful for clinical practice were derived.
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The roles of endothelial nitric oxide synthase gene polymorphisms in diabetes mellitus and its associated vascular complications: a systematic review and meta-analysis.
Dong, J, Ping, Y, Wang, Y, Zhang, Y
Endocrine. 2018;(2):412-422
Abstract
PURPOSE The roles of endothelial nitric oxide synthase (eNOS) gene polymorphisms in diabetes mellitus (DM) were intensively analyzed, but the results of these studies were inconsistent. Therefore, we performed this study to better assess the relationship between eNOS genetic variations and DM. METHODS Eligible studies were searched in PubMed, Medline, Embase, and Web of Science. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess correlations between eNOS polymorphisms and DM. RESULTS A total of 91 studies were finally included in our analyses. Significant associations with the susceptibility to DM were detected for the rs891512, rs1799983, rs2070744, and rs869109213 polymorphisms. As for vascular complications in DM, significant associations with the susceptibility to diabetic nephropathy were detected for the rs1799983 and rs2070744 polymorphisms. In addition, we also found that the rs1799983 polymorphism was significantly associated with the susceptibility to peripheral artery disease, whereas the rs2070744 polymorphism was significantly associated with the susceptibility to coronary artery disease in DM patients. Further subgroup analyses on the basis of type of disease and ethnicity of participants showed similar positive results. CONCLUSIONS In conclusion, our findings indicate that rs891512, rs1799983, rs2070744, and rs869109213 polymorphisms may serve as genetic biomarkers of DM, while rs1799983, rs2070744, and rs869109213 polymorphisms may contribute to the development of vascular complications in DM.
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A variant in the SCN10A enhancer may affect human mechanical pain sensitivity.
Duan, G, Sun, J, Li, N, Zheng, H, Guo, S, Zhang, Y, Wang, Q, Ying, Y, Zhang, M, Huang, P, et al
Molecular pain. 2018;:1744806918763275
Abstract
Expression of Nav1.8, encoded by SCN10A, can affect pain transmission and thus mediate the human pain phenotype. In the current study, we assessed whether the variant rs6801957, located in the SCN10A enhancer region, may have the potential to affect human pain. Through dual-luciferase reporter assays in 293T cells, we found that the SCN10A enhancer A (Enh-A) increased the activity of the SCN10A promoter ( P < 0.05). Additionally, in a cohort of 309 healthy women, mutant rs6801957 A/A was found to have a significant association with decreased human experimental mechanical pain sensitivity ( P < 0.05). We then found that mutant genotype A/A suppressed the increased effect of Enh-A compared with wild-type G/G ( P < 0.05). The association between rs6801957 and human experimental mechanical pain sensitivity was further validated in a larger cohort of 1005 women ( P < 0.05). In conclusion, these results demonstrated that the variant rs6801957 and Enh-A may affect SCN10A gene expression and play an important role in human mechanical pain sensitivity.
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Analyzing large-scale samples confirms the association between rs16892766 polymorphism and colorectal cancer susceptibility.
Liao, M, Wang, G, Quan, B, Qi, X, Yu, Z, Feng, R, Zhang, L, Jiang, Y, Zhang, Y, Liu, G
Scientific reports. 2015;:7957
Abstract
Colorectal cancer (CRC) is a common complex disease caused by the combination of genetic variants and environmental factors. Genome-wide association studies (GWAS) have been performed and reported some novel CRC susceptibility variants. The rs16892766 (8q23.3) polymorphism was first identified to be significantly associated with CRC in European ancestry. The following studies investigated this association in Chinese, Japanese, Romanian, Swedish, African American, European American, and Croatian populations. These studies reported consistent and inconsistent results. Here, we reevaluated this association using the relatively large-scale samples from 13 studies (N = 59737, 26237 cases and 33500 controls) using a meta-analysis by searching the PubMed, Google Scholar and CRCgene databases. We observed no significant heterogeneity among the included studies. Our results showed significant association between rs16892766 polymorphism and CRC (P = 1.33E-35, OR = 1.23, 95% CI 1.20-1.27). Collectively, our analysis further supports previous findings that the rs16892766 polymorphism is significantly associated with CRC susceptibility. We believe that our findings will be very useful for future genetic studies on CRC.
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Association of polymorphisms in drug transporter genes (SLCO1B1 and SLC10A1) and anti-tuberculosis drug-induced hepatotoxicity in a Chinese cohort.
Chen, R, Wang, J, Tang, S, Zhang, Y, Lv, X, Wu, S, Xia, Y, Deng, P, Ma, Y, Tu, D, et al
Tuberculosis (Edinburgh, Scotland). 2015;(1):68-74
Abstract
This study investigated the association between genetic variants in two hepatic uptake transporter genes (SLCO1B1 and SLC10A1) and the risk of anti-tuberculosis drug-induced hepatotoxicity (ATDH) in a Chinese cohort. The frequencies and distributions of single nucleotide polymorphisms (SNPs) and haplotypes of these genes were compared among 89 incident ATDH cases and 356 matched ATDH-free controls using a multivariate conditional logistic regression analysis. After correction for potential confounding factors, significant differences were found in polymorphism of rs4149014 under an addictive model (P = 0.008) and a recessive model (P = 0.016). The result of haplotype analysis suggested that patients carrying at least one SLCO1B1*15 haplotype had a higher risk of ATDH (odds ratio (OR) = 1.74, 95% confidence intervals (CI): 1.04-2.90, P = 0.034) in comparison with those carrying SLCO1B1*1a or SLCO1B1*1b haplotypes. These findings indicate that genetic variants of SLCO1B1 are associated with the development of ATDH in Chinese population.
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Common variants of ATP1A3 but not ATP1A2 are associated with Chinese genetic generalized epilepsies.
Qu, J, Yang, ZQ, Zhang, Y, Mao, CX, Wang, ZB, Mao, XY, Zhou, BT, Yin, JY, He, H, Long, HY, et al
Journal of the neurological sciences. 2015;(1-2):56-62
Abstract
OBJECTIVE ATP1A2 and ATP1A3 are genes that code for catalytic subunits of Na/K-ATPases, which play important roles in the basal electrophysiological states of nerve cells. The aim of this study was to investigate whether genetic polymorphisms of ATP1A2 and ATP1A3 influence susceptibility to genetic generalized epilepsies (GGEs) and the efficacy of anti-epileptic drugs in a Chinese population. METHOD Six ATP1A2 tagged single-nucleotide polymorphisms (tagSNPs) and two ATP1A3 tagSNPs were were genotyped by allele-specific MALDI-TOF mass spectrometry in 484 Chinese GGE patients (280 drug-responsive and 204 drug-resistant patients) and 284 healthy controls. RESULTS Significant differences were found in the frequencies of the ATP1A3 rs8107107 C allele and the CC genotype between the GGEs and the healthy controls (11% vs. 15%, odds ratio (OR)=0.807 (0.68-0.960), p=0.021 and 0.4% vs. 3.2%, OR=0.121 (0.026-0.565), p=0.002, respectively). The frequency of the rs8107107 CT+CC genotype was significantly lower among the GGE patients than among the healthy controls (15% vs. 26.8%, OR=0.327 (0.248-0.942), p=0.001). No significant differences in the frequencies of six ATP1A2 tagSNPs or ATP1A2 haplotypes were found between the GGEs and the healthy controls. No tagSNPs were involved in anti-epileptic drug resistance. CONCLUSION Our findings demonstrated that common variants of ATP1A3 but not ATP1A2 were associated with the susceptibility to GGEs in a Chinese population, which indicates that the ATP1A3 gene plays a significant role in the pathophysiology of genetic generalized epilepsies.
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Evaluating the association between CACNA1C rs1006737 and schizophrenia risk: A meta-analysis.
Jiang, H, Qiao, F, Li, Z, Zhang, Y, Cheng, Y, Xu, X, Yu, L
Asia-Pacific psychiatry : official journal of the Pacific Rim College of Psychiatrists. 2015;(3):260-7
Abstract
INTRODUCTION Genetic analyses including genome-wide association studies have reported an intronic single nucleotide polymorphism (SNP) rs1006737 in CACNA1C gene (encoded calcium channel, voltage-dependent, L type, alpha 1C subunit) as a risk factor for schizophrenia in European populations. The replications in other ethnic populations such as East Asians have also been conducted, but the results were inconsistent, either likely due to the limited sample size of single study or genetic heterogeneity between continental populations on this locus. METHODS We performed a comprehensive meta-analysis of all available samples from existing studies of East Asian populations, including a total of 9,432 cases and 10,661 controls, to further confirm whether CACNA1C rs1006737 is an authentic risk SNP for schizophrenia in East Asian populations. RESULTS Our results revealed a significant association between rs1006737 and schizophrenia (allelic model, P = 4.39 × 10(-6) , pooled odds ratio [OR] = 1.20), and the results were much strengthened when the European and East Asian samples were combined together (P = 2.40 × 10(-17) , pooled OR = 1.12). There is no significant heterogeneity or publication bias between individual studies, and removal of any single study still remained significant associations between rs1006737 and schizophrenia. DISCUSSION Our results further confirmed that rs1006737 should be categorized as an authentic risk SNP for schizophrenia in the general populations.
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Rs7193343 polymorphism in zinc finger homeobox 3 (ZFHX3) gene and atrial fibrillation: an updated meta-analysis of 10 case-control comparisons.
Zhai, C, Cong, H, Liu, Y, Zhang, Y, Liu, X, Zhang, H, Ren, Z
BMC cardiovascular disorders. 2015;:58
Abstract
BACKGROUND The previous genome-wide studies have shown that rs7193343 single-nucleotide polymorphism (SNP) in zinc finger homeobox 3 (ZFHX3) gene correlate with risk of atrial fibrillation (AF). However, the distribution of this SNP differs significantly among various populations. The present study was to investigate whether combined evidence shows the association between ZFHX3 rs7193343 SNP and the risk of AF in various populations. METHODS A systematic search of all studies published through Dec 2014 was conducted using the Medline, Embase, WanFang, ScienceDirect, CNKI, and OVID databases. The case-control studies that evaluated an association between rs7193343 SNP and risk of AF were identified. The association between the ZFHX3 rs7193343 SNP and AF susceptibility was assessed using genetic models. RESULTS We collected 10 comparisons from six studies for rs7193343 SNP, including 1037 cases and 4310 controls in Asian, 5583 cases and 38215 controls in Caucasian, and then performed an updated meta-analysis and subgroup analysis based on ethnicity. In overall population, the occurrence of AF was found to be associated with T-allelic of rs7193343 SNP in ZFHX3 (OR =1.17, 95% CI 1.10-1.26). In subgroup analysis, we observed there was significant association between T-allele of rs7193343 and risk of AF in Caucasian subgroups (OR =1.20, 95% CI 1.12-1.30), but no statistically significance (OR = 1.07, 95% CI 0.92-1.24) in Asian population. CONCLUSION In Caucasian population, genetic variant rs7193343 SNP is associated with risk of AF in Caucasian population. However, no association is found in Asian population based on the current evidence. Further studies with larger sample size involving case-control populations with multiple ethnics are still required in the future.