Angiotensin I-converting enzyme polymorphisms, ACE level and blood pressure among Nigerians, Jamaicans and African-Americans

Abstract

The genes in the renin -angiotensin system are important physiologic candidates in studies of the genetic susceptibility to hypertension. Limited information has been available in most studies on the extent of variation in the candidate loci or the modifying effects of different environmental settings. We consequently genotyped 13 polymorphisms at the angiotensin I-converting enzyme (ACE) locus at an average distance of 2 kb in 2776 family members from Nigeria, Jamaica and an African-American community in the US. Allele and haplotype frequencies were similar in the three populations, with modest evidence of European admixture in the US. Two markers were consistently associated with ACE level in the three samples and the proportion of variance accounted for by ACE8 was similar in the three groups. No evidence of consistent association of single markers was noted with blood pressure across the three population samples, however. Likewise, in a haplotype-based analysis, despite significant associations within each population, the findings were not replicated consistently across all three samples. We did observe, however, that the overtransmitted haplotypes among hypertensives were drawn from a single clade, suggesting that susceptibility may cluster in patterns not captured directly by our markers.

Haplotype variation in the ACE gene in global populations, with special reference to India, and an alternative model of evolution of haplotypes

“…Haplotype data for three African [Nigerians, Afro-Americans, Jamaicans (Bouzekri et al 2004), and two Caucasian [British (Keavney et al 1998) and French (Villard et al 1996)] populations were collated. These haplotypes were collapsed to include the 9 polymorphic loci rs4277405, rs4459609, rs1800764, rs4291, rs4292(all regulatory), rs4309, rs4331, rs4343 (all exonic), and rs4340(intronic) to make the data comparable (Supplementary Materials & Methods We genotyped these nine loci ( Fig.…”

“…Their frequencies showed statistically significant differences (P \ 0.0001) across populations (Supplementary Table 2). In the African populations, three major haplotypes CCCTTCGIA (12-19%), TACATCADG (16-36%), and TACATCADA (25-29%) were present (Bouzekri et al 2004). The two major haplotypes in the non-African populations were TATATTGIA (38-72%) and CCCTCCADG (19-40%).…”

Finding Associations in Dense Genetic Maps: A Genetic Algorithm Approach

“…Linkage and segregation analysis have shown that circulating angiotensin-I converting enzyme (ACE) levels are infl uenced by a major quantitative (or continuous) trait locus that maps within the ACE gene [Bouzekri et al, 2004]. The ACE gene may be viewed as a candidate gene for (essential) hypertension.…”

“…Data were available on 738 Nigerian individuals genotyped for 13 SNPs in a 26-kb region on the ACE gene. The thirteen polymorphic sites have been described elsewhere [Bouzekri et al, 2004] as ACE1-ACE5, ACEs12, ACEs11, ACE6, NewACE6, ACE7, I/D, ACE8 and ACE9, but we will refer to them as SNPs 1-13, respectively. These data are a subset of a larger study consisting of Jamaicans and African-Americans, that are less homogeneous because of admixture [Bouzekri et al, 2004].…”

“…The thirteen polymorphic sites have been described elsewhere [Bouzekri et al, 2004] as ACE1-ACE5, ACEs12, ACEs11, ACE6, NewACE6, ACE7, I/D, ACE8 and ACE9, but we will refer to them as SNPs 1-13, respectively. These data are a subset of a larger study consisting of Jamaicans and African-Americans, that are less homogeneous because of admixture [Bouzekri et al, 2004]. The phenotype of interest was standardized ACE concentration, a continuous variable (mean -0.04, median -0.16, range -2.16 to 3.51).…”