Dataset Information

Association between the CYP4A11 T8590C variant and essential hypertension: new data from Han Chinese and a meta-analysis.

ABSTRACT:

Objective

CYP4A11 oxidizes endogenous arachidonic acid to 20-hydroxyeicosatetraenoic acid, a renal vasoconstrictor and natriuretic in humans. Previous studies demonstrated an association between a functional variant (T8590C) of CYP4A11 and essential hypertension, though with conflicting results. To elucidate this relationship, a case-control study and meta-analysis were performed to assess the possible association of essential hypertension with CYP4A11 genetic variations.

Methods

Associations between the T8590C polymorphism and essential hypertension were examined in 328 unrelated cases and 297 age-matched controls in Han Chinese individuals. High-resolution melting was used to identify the CYP4A11 variant. To further investigate the association, we conducted a meta-analysis including eight studies published previously in July 2012.

Results

The frequency of the CYP4A11 T8590C polymorphism showed no significant difference between cases and controls (all P>0.05). However, the meta-analysis showed that the CYP4A11 T8590C polymorphism may increase the risk of essential hypertension in an additive model (OR: 1.15, 95% CI: 1.02-1.29, P?=?0.02), a dominant model (OR: 1.06, 95% CI: 1.01-1.32, P?=?0.03), a recessive model (OR: 1.52, 95% CI: 1.15-2.02, P?=?0.003) and a homozygote contrast (OR: 1.38, 95% CI: 1.07-1.78, P?=?0.01). Also, a significant relationship was observed among Caucasians in the additive model, the homozygote contrast, the recessive model and the dominant model (all P<0.05). However, no association was observed in an Asian population (all P>0.05).

Conclusions

This meta-analysis suggests there is a significant association between the CYP4A11 T8590C variant and essential hypertension, especially in Caucasians. The case-control study did not find a significant association among the Han Chinese population, but the controls were poorly matched and meaningful conclusions cannot therefore be made. Further large-scale studies are needed to clarify whether the CYP4A11 T8590C polymorphism is associated with hypertension risk in Asians or has a gender-specific effect.

SUBMITTER: Yan HC

PROVIDER: S-EPMC3836999 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association between the CYP4A11 T8590C variant and essential hypertension: new data from Han Chinese and a meta-analysis.

Yan Hua-Cheng HC Liu Jun-Hua JH Li Jian J He Bao-Xia BX Yang Liang L Qiu Jian J Li Liang L Ding Da-Peng DP Shi Lei L Zhao Shu-Jin SJ

PloS one 20131121 11

<h4>Objective</h4>CYP4A11 oxidizes endogenous arachidonic acid to 20-hydroxyeicosatetraenoic acid, a renal vasoconstrictor and natriuretic in humans. Previous studies demonstrated an association between a functional variant (T8590C) of CYP4A11 and essential hypertension, though with conflicting results. To elucidate this relationship, a case-control study and meta-analysis were performed to assess the possible association of essential hypertension with CYP4A11 genetic variations.<h4>Methods</h4> ...[more]

PMID: 24278241

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Project description:BackgroundElastogenesis of elastic extracellular matrix (ECM) which was recognized as a major component of blood vessels has been believed for a long time to play only a passive role in the dynamic vascular changes of typical hypertension. Emilin1 gene participated in the transcription of ECM's formation and was recognized to modulate links TGF-beta maturation to blood pressure homeostasis in animal study. Recently relevant advances urge further researches to investigate the role of Emilin1 gene in regulating TGF-beta signals involved in elastogenesis and vascular cell defects of essential hypertension (EH).MethodsWe designed a two-stage case-control study and selected three single nucleotide polymorphisms (SNPs), rs3754734, rs2011616 and rs2304682 from the HapMap database, which covered Emilin1 gene. Totally 2,586 subjects were recruited from the International Collaborative Study of Cardiovascular Disease in Asia (InterASIA). In stage 1, all the three SNPs of the Emilin1 gene were genotyped and tested within a subsample including 503 cases and 490 controls, significant SNPs would enter into stage 2 including 814 cases with hypertension and 779 controls and analyze on the basis of testing total 2,586 subjects.ResultsIn stage 1, single locus analyses showed that SNPs rs3754734 and rs2011616 had significant association with EH (P < 0.05). In stage 2, weak association for dominant model were observed by age stratification and odds ratio (ORs) of TG+GG vs. TT of rs3754734 were 0.768 (0.584-1.009), 0.985 (0.735-1.320) and 1.346 (1.003-1.806) in < 50, 50-59 and > or = 60 years group and ORs of GA+AA vs. GG of rs2011616 were 0.745 (0.568-0.977), 1.013 (0.758-1.353) and 1.437 (1.072-1.926) in < 50, 50-59 and > or = 60 years group respectively. Accordingly, significant interactions were detected between genotypes of rs3754734 and rs2011616 and age for EH, and ORs were 1.758 (1.180-2.620), P = 0.006 and 1.903 (1.281-2.825), P = 0.001, respectively. Results of haplotypes analysis showed that there weren't any haplotypes associated with EH directly, but the interaction of hap2 (GA) and age-group found to be significant after being adjusted for the covariates, OR was 1.220 (1.031-1.444), P value was 0.020.ConclusionOur findings don't support positive association of Emilin1 gene with EH, but the interaction of age and genotype variation of rs3754734 and rs2011616 might increase the risk to hypertension.

Dataset Information

Association between the CYP4A11 T8590C variant and essential hypertension: new data from Han Chinese and a meta-analysis.

Objective

Methods

Results

Conclusions

Publications

Association between the CYP4A11 T8590C variant and essential hypertension: new data from Han Chinese and a meta-analysis.

Similar Datasets

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