Five polymorphisms in gene candidates for cardiovascular disease in Afro‐Brazilian individuals

Abstract

Associations of polymorphisms in the angiotensin I-converting enzyme (ACE), apolipoprotein B (APOB) and apolipoprotein E (APOE) genes with hypertension and variations in lipid serum levels were evaluated in 184 Afro-Brazilians with a familial history of coronary artery disease (CAD). ACE (Ins/Del) and APOB (Ins/Del, XbaI, and EcoRI) and APOE (HhaI) polymorphisms were determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analyses on agarose, and polyacrylamide gel electrophoresis. Serum lipids were measured by means of routine enzymatic assays. The results showed a high frequency of hypertension (44%) in Afro-Brazilians that was increased in subjects >40 years old and those with a blood mass index (BMI) higher than 25 kg/m(2) (P<0.001). The ACE Del allele was associated with hypertension in men >40 years old (P<0.05). APOE (HhaI) and APOB (XbaI and Ins/Del) polymorphisms were not associated with hypertension or variations in serum concentrations of lipids, while subjects with the APOB E- allele had higher low-density lipoprotein cholesterol (LDL-C) levels than E+ carriers (P<0.05). These results suggest that ACE Ins/Del polymorphism is associated with hypertension, and APOB EcoRI polymorphism is associated with LDL-C variation in Afro-Brazilians.

Worldwide spatial genetic structure of angiotensin-converting enzyme gene: a new evolutionary ecological evidence for the thrifty genotype hypothesis

“…28 Therefore, under the ancient African environmental condition, which was arid and hot, the sodium and water retaining capacity was crucial, carrying D allele frequency could be favored, given that the higher the D allele frequency, the higher the activity of serum ACE level. 19,20 When each population reached their new location and settled down, they were subject to new different evolutionary forces, such as cold temperatures and humid surroundings, which likely became important selective forces after human out-of-Africa expansion.…”

“…The most impressive case is the angiotensin-converting enzyme (ACE) gene with a common polymorphism represented by the insertion (I) or deletion (D) of a 287-bp AluYa5 element inside intron 16 on chromosome 17q23, 19 which is associated with many cardiocerebral vascular diseases (CVDs). 20,21 Moreover, studies on ACE I/D polymorphisms have indicated that the Alu insertions are shown to be absent from the genomes of a number of non-human primates, consistent with the rise in human genetic polymorphisms sometime after the human/African anthropoid divergence, 22 which suggests that D allele is the ancestral allele 23,24 and its evolutionary history could be used to provide evidence for the 'thrifty genotype' hypothesis. On the other hand, accumulating evidence has suggested that genetic susceptibility to CVD as well as salt avidity and cardiovascular reactivity are ancestral and were likely magnified during the early human evolution before the out-of-Africa expansion of anatomically modern humans [25][26][27] and it is due to diverse selection pressure during the out-of-Africa expansion that occurred 30 000-100 000 years ago, among which, the most important selection pressure was climate.…”

“…The thrifty D became deleterious, as it increases susceptibility to hypertension and other hypertension-related diseases. 20,21 Consequently, some individuals who carried D allele were eliminated from the population because of hypertension or other hypertension-related diseases. If the above assumption is true, the frequency of D allele in Africans should be higher, and from Africa, following the route of out-of-Africa expansion, an obvious decreasing geographic genetic cline should be detected.…”

Impact of ACE and ApoE polymorphisms on myocardial perfusion: correlation with myocardial single photon emission computed tomographic imaging

“…9 Previous studies have shown an association of ApoE gene polymorphisms with variation serum concentrations, hypertension and risk of myocardial infarction. 10,11 Our results show the first evidence of an association of ACE and ApoE polymorphisms with myocardial perfusion and suggest that the proposed effect of the abovementioned polymorphisms may have important influence on early patient risk stratification.…”

“…Previous studies have shown an association of ApoE gene polymorphisms with variation serum concentrations, hypertension and risk of myocardial infarction. 10,11 It has been shown that individuals with the e2 allele had lower risk of myocardial infarction and higher in e4 carriers, with a decrease of e4 allele frequency across the countries from Northern to Southern Europe, which follows the gradient of coronary heart disease mortality rates. 11,37 These results are consistent with the findings from this study in which the e4 allele and its genotypes have priority among patients with moderate and severe abnormal myocardial perfusion.…”