Key result
Apelin -1860T>C mutant allele linked to ~3.6-fold higher CAD risk.
Why the study?
Candidate polymorphisms in apelin and AGTRL1 genes were previously identified in family-based association with hypertension, requiring validation in a larger independent population.
Case-Control (n=222)
Yes
Odds Ratio: 3.56 (95% CI 1.37–9.27)
p-value: p=0.009
Apelin -1860T>C C allele association with CAD risk should not change practice; leaves open replication and causal inference in broader populations.
BACKGROUND AND OBJECTIVE: We have recently resequenced apelin and AGTRL1 genes to identify candidate polymorphisms in family-based association with hypertension and related phenotypes. In this study, we aimed to determine and replicate these polymorphisms via a larger, independent case-control study in Shanghai Han Chinese. METHODS: Two polymorphisms [rs3761581 (A/C) and T-1860C] in apelin gene and two [rs7119375 (G/A), rs10501367 (G/A)] in AGTRL1 gene were genotyped using the TaqMan assay among 969 patients diagnosed with essential hypertension and 980 age and sex-matched controls. Data were analyzed using Haplo.stats program. RESULTS: In single-locus analysis, significant differences were observed in allele distribution of rs3761581 (P = 0.0156) in men and in rs7119375 (P = 0.0488) genotype distribution in women between patients and controls. Haplotype analysis indicated that haplotypes C-C-G-G (in order of T-1860C, rs3761581, rs7119375 and rs10501367) [adjusted odds ratio (ORadjusted) = 1.67, P = 0.0061] and T-A-A-A (ORadjusted = 1.62, P = 0.0008) conferred an increased risk for hypertension after adjustment for age, onset age, body mass index (BMI) and waist-to-hip ratio, whereas haplotype C-C-A-A (ORadjusted = 0.33, P = 0.0048) conferred a protective effect. In women, increased risk for hypertension was seen for haplotypes T-A-G-G (ORadjusted = 1.30, P = 0.0051), C-C-G-G (ORadjusted = 2.86, P < 0.0001), T-A-A-A (ORadjusted = 1.66, P = 0.0003) and C-C-A-A (ORadjusted = 2.65, P < 0.0001), whereas decreased risk was seen for haplotypes C-A-G-G (ORadjusted = 0.48, P < 0.0001) and T-C-G-G (ORadjusted = 0.40, P < 0.0001). Further haplotype-phenotype analyses indicated the robustness of these associations. For example, haplotype T-A-A-A was significantly associated with obesity index (BMI and waist-to-hip ratio) in both sexes and blood pressures in men (P-sim < 0.05). CONCLUSION: In this exploratory pilot case-control study, we found robust haplotype-based and haplotype-phenotype associations of four well characterized polymorphisms in apelin-AGTRL1 system with hypertension and related phenotypes.
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Niu et al. (2010) conducted a case-control in Coronary artery disease (n=222). APLN -1860T>C polymorphism (C allele) vs. Wild-type T allele was evaluated on Coronary artery disease susceptibility (OR 3.56, 95% CI 1.37-9.27, p=0.009). The mutant C allele of the apelin -1860T>C polymorphism was independently associated with a 3.56-fold increased risk of coronary artery disease compared to the wild-type T allele in a Syrian cohort.
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