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Associations between PPARG polymorphisms and the risk of essential hypertension.

ABSTRACT: BACKGROUND:Peroxisome proliferator-activated receptor gamma (PPARG) plays an important role in the pathogenesis and maintenance of essential hypertension (EH). It has been suggested that polymorphisms of PPARG are associated with the risk of EH. However, findings to date remain controversial. To elucidate the associations between the PPARG Pro12Ala and C161T polymorphisms and EH risk, a meta-analysis was carried out. METHODS:A comprehensive literature search of PubMed, Embase, CNKI (Chinese National Knowledge Infrastructure), VIP and Wanfang databases was conducted. The pooled odds ratios (ORs) and 95% confidence interval (CI) were calculated to estimate the size of the effect using the random-effects model. At the same time, the pooled standardized mean difference (SMD) with 95% CI was used for the meta-analysis of the PPARG Pro12Ala polymorphism and blood pressure. RESULTS:Finally, Fifteen papers (seventeen studies) including 4,151 cases and 4,997 controls to evaluate the association of the PPARGPro12Ala polymorphism and EH risk, were included in this study. Overall, the results suggested that Ala allele was associated with the decreased EH risk (for allelic model, OR = 0.757, 95%CI: 0.624-0.918, P = 0.005; for dominant model, OR = 0.771, 95%CI: 0.627-0.946, P = 0.013). The subgroup analysis stratified by ethnicity showed that the significant association between the PPARG Pro12Ala polymorphism and EH was only detected in the Asian subgroup. There was no difference in blood pressure values between Ala carriers and non-carriers. For the C161T polymorphism, only 5 studies comprising 1,118 cases and 1,357 controls met the inclusion criteria. The overall results showed that the PPARG C161T polymorphism was not associated with the risk of EH. But in the subgroup analysis, we found that the PPARG C161T polymorphism significantly associated with the risk of EH in the Asian subgroup (for allelic model, OR = 0.719, 95% CI: 0.537-0.963, P = 0.027; for dominant model, OR = 0.653, 95% CI: 0.439-0.972, P = 0.036). CONCLUSION:Our meta-analysis suggested that the PPARG polymorphisms might be associated with the risk of EH.

SUBMITTER: Cai G

PROVIDER: S-EPMC5519177 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Associations between PPARG polymorphisms and the risk of essential hypertension.

Cai Gaojun G Zhang Xinyong X Weng Weijin W Shi Ganwei G Xue Sheliang S Zhang Bifeng B

PloS one 20170720 7

<h4>Background</h4>Peroxisome proliferator-activated receptor gamma (PPARG) plays an important role in the pathogenesis and maintenance of essential hypertension (EH). It has been suggested that polymorphisms of PPARG are associated with the risk of EH. However, findings to date remain controversial. To elucidate the associations between the PPARG Pro12Ala and C161T polymorphisms and EH risk, a meta-analysis was carried out.<h4>Methods</h4>A comprehensive literature search of PubMed, Embase, CNK ...[more]

PMID: 28727849

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Project description:BackgroundDysregulations of AQP7 and AQP9 were found to be related to lipid metabolism abnormality, which had been proven to be one of the mechanisms of stroke. However, limited epidemiological studies explore the associations between AQP7 and AQP9 and the risk of stroke among patients with hypertension in China.AimsWe aimed to investigate the associations between genetic variants in AQP7 and AQP9 and the risk of stroke among patients with hypertension, as well as to explore gene-gene and gene-environment interactions.MethodsBaseline blood samples were drawn from 211 cases with stroke and 633 matched controls. Genomic DNA was extracted by a commercially available kit. Genotyping of 5 single nucleotide polymorphisms (SNPs) in AQP7 (rs2989924, rs3758269, and rs2542743) and AQP9 (rs57139208, rs16939881) was performed by the polymerase chain reaction assay with TaqMan probes.ResultsParticipants with the rs2989924 GG genotype were found to be with a 1.74-fold increased risk of stroke compared to those with the AA+AG genotype, and this association remained significant after adjustment for potential confounders (odds ratio (OR): 1.74, 95% confidence interval (CI): 1.23-2.46). The SNP rs3758269 CC+TT genotype was found to be with a 33% decreased risk of stroke after multivariate adjustment (OR: 0.67, 95% CI: 0.45-0.99) compared to the rs3758269 CC genotype. The significantly increased risk of stroke was prominent among males, patients aged 60 or above, and participants who were overweight and with a harbored genetic variant in SNP rs2989924. After adjusting potential confounders, the SNP rs3758269 CT+TT genotype was found to be significantly associated with a decreased risk of stroke compared to the CC genotype among participants younger than 60 years old or overweight. No statistically significant associations were observed between genotypes of rs2542743, rs57139208, or rs16939881 with the risk of stroke. Neither interactions nor linkage disequilibrium had been observed in this study.ConclusionsThis study suggests that SNPs rs2989924 and rs3758269 are associated with the risk of stroke among patients with hypertension, while there were no statistically significant associations between rs2542743, rs57139208, and rs16939881 and the risk of stroke being observed.

Project description:BACKGROUND:Since the 1990s, there have been a lot of research on single-nucleotide polymorphism (SNP) and different diseases, including many studies on 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphism and essential hypertension (EH). Nevertheless, their conclusions were controversial. So far, six previous meta-analyses discussed the internal relationship between the MTHFR polymorphism and EH, respectively. However, they did not evaluate the credibility of the positive associations. To build on previous meta-analyses, we updated the literature by including previously included papers as well as nine new articles, improved the inclusion criteria by also considering the quality of the papers, and applied new statistical techniques to assess the observed associations. OBJECTIVES:This study aims to explore the degree of risk correlation between two MTHFR polymorphisms and EH. METHODS:PubMed, EMBASE, the Cochrane Library, CNKI, and Wan Fang electronic databases were searched to identify relevant studies. We evaluated the relation between the MTHFR C677T (rs1801133) and A1298C (rs1801131) polymorphisms and EH by calculating the odds ratios (OR) as well as 95% confidence intervals (CI). Here we used subgroup analysis, sensitivity analysis, cumulative meta-analysis, assessment of publication bias, meta-regression meta, False-positive report probability (FPRP), Bayesian false discovery probability (BFDP), and Venice criterion. RESULTS:Overall, harboring the variant of MTHFR C677T was associated with an increased risk of EH in the overall populations, East Asians, Southeast Asians, South Asians, Caucasians/Europeans, and Africans. After the sensitivity analysis, positive results were found only in the overall population (TT vs. CC: OR = 1.14, 95% CI: 1.00-1.30, P h = 0.032, I 2 = 39.8%; TT + TC vs. CC: OR = 1.15, 95% CI: 1.01-1.29, P h = 0.040, I 2 = 38.1%; T vs. C: OR = 1.14, 95% CI: 1.04-1.25, P h = 0.005, I 2 = 50.2%) and Asian population (TC vs. CC: OR = 1.14, 95% CI: 1.01-1.28, P h = 0.265, I 2 = 16.8%; TT + TC vs. CC: OR = 1.17, 95% CI: 1.04-1.30, P h = 0.105, I 2 = 32.9%; T vs. C: OR = 1.10, 95% CI: 1.02-1.19, P h = 0.018, I 2 = 48.6%). However, after further statistical assessment by FPRP, BFDP, and Venice criteria, the positive associations reported here could be deemed to be false-positives and present only weak evidence for a causal relationship. In addition, when we performed pooled analysis and sensitivity analysis on MTHFR A1298C; all the results were negative. CONCLUSION:The positive relationships between MTHFR C677T and A1298C polymorphisms with the susceptibility to present with hypertension were not robust enough to withstand statistical interrogation by FPRP, BFDP, and Venice criteria. Therefore, these SNPs are probably not important in EH etiology.

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Associations between PPARG polymorphisms and the risk of essential hypertension.

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Associations between PPARG polymorphisms and the risk of essential hypertension.

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