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Association study: the aminopeptidase a gene and essential hypertension.

ABSTRACT: Aminopeptidase A (APA) cleaves the N-terminal aspartyl acid residue of angiotensin II (Ang II) to produce angiotensin III (Ang III). It has been reported that the APA knockout mouse exhibits elevated blood pressure. Therefore, the APA gene is thought to be a susceptibility gene for essential hypertension (EH). However, extensive studies have yet to define the relationship between the APA gene and EH. The aims of this study were to genotype some of the single nucleotide polymorphisms (SNPs) for the human APA gene and to perform a haplotype-based case-control study to further assess the association between and the APA gene and EH. We performed a genetic association study using SNPs in 227 EH patients and 221 age-matched normotensive (NT) individuals. Although the overall distribution of the genotype did not significantly differ between the EH and NT groups when the entire group of subjects were evaluated, the frequency of rs2290105 did differ between the two when just women were included in the analysis. The haplotype-based case-control analysis also revealed a significant difference between the women of the EH and NT groups. The A-T-A-C haplotype was significantly higher in the EH versus the NT group. These results suggest that rs2290105 and the A-T-A-C haplotype of the APA gene are genetic markers for EH, and that APA or a neighboring gene might be a susceptibility gene for EH.

SUBMITTER: Sano M

PROVIDER: S-EPMC3614582 | biostudies-literature | 2005 Jun

REPOSITORIES: biostudies-literature

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Association study: the aminopeptidase a gene and essential hypertension.

Sano Morihiko M Kuroi Nobuhiro N Nakayama Tomohiro T Sato Naoyuki N Izumi Yoichi Y Soma Masayoshi M

International journal of biomedical science : IJBS 20050601 1

Aminopeptidase A (APA) cleaves the N-terminal aspartyl acid residue of angiotensin II (Ang II) to produce angiotensin III (Ang III). It has been reported that the APA knockout mouse exhibits elevated blood pressure. Therefore, the APA gene is thought to be a susceptibility gene for essential hypertension (EH). However, extensive studies have yet to define the relationship between the APA gene and EH. The aims of this study were to genotype some of the single nucleotide polymorphisms (SNPs) for t ...[more]

PMID: 23674950

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Project description:BACKGROUND: Elastogenesis 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). METHODS: We 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. RESULTS: In 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. CONCLUSION: Our 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.

Project description:Essential hypertension (EH) is influenced by various environmental and genetic factors. Nitric oxide is important for the functional integrity of the vascular endothelium and is produced in endothelial cells by the enzyme endothelial nitric oxide synthase (eNOS). EH has a strong genetic component, and the NOS3 gene, which encodes eNOS, represents an interesting candidate for contribution to the phenotype. The most clinically relevant polymorphisms in the NOS3 gene are rs1799983 in exon 7 (encoding Glu298Asp), a variable number tandem repeat (VNTR) in intron 4, and rs2070744 (T-786C) in the promoter region. This study aims to investigate the association between these three polymorphisms in the NOS3 gene and EH in Sudanese patients.Hypertensive patients (n?=?157) > 18 years of age with established hypertension from various hospitals in Khartoum, and controls (n?=?85) > 18 years of age and with blood pressure measurements <140/90, were included in this case control study. Genotypes at the NOS3 variants were determined using TaqMan and polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analyses. Genotype and allele frequencies were compared between the two groups by ?2 analysis, and differences were expressed as odds ratios with 95% confidence intervals (CIs). P values <0.05 were considered statistically significant.The rs2070744 polymorphism in NOS3 was found to be associated with EH in the Sudanese population as the patients group had higher frequency of CC genotype compared with the controls (6.6% vs 6.1%, p?=?0.02). Considering a dominant inheritance model, the frequency of TC + CC genotypes in patients was significantly higher than that in the control subjects (52.6% vs 34.1%, respectively; p < 0.01), with an odds ratio (95% CI) of 2.14 (1.23-3.74). In addition, the C allele was more frequent in the patients than the control group (29.6% vs 20%, p?=?0.03, OR?=?1.84 (1.15-2.93)). The c allele of intron 4 VNTR was reported in >1% of the Sudanese population under study.The results of this study indicated that the rs2070744 polymorphism in NOS3 may be a genetic susceptibility factor for EH in the Sudanese population. The c allele of intron 4 VNTR is not rare in the Sudanese population.

Dataset Information

Association study: the aminopeptidase a gene and essential hypertension.

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Association study: the aminopeptidase a gene and essential hypertension.

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