Lack of genetic association between the angiotensin-converting enzyme gene insertion/deletion polymorphism and longevity in a Han Chinese population

Abstract

Introduction. The insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE) gene has been reported to associate with human longevity. However, little information is available in a Han Chinese longevity population. Therefore, we investigated the association of the ACE gene insertion/ deletion polymorphism with longevity in a Han Chinese population. Materials and methods. We compared the distribution of ACE insertion/deletion genotype and allele frequencies in two groups: a longevity group (399 subjects) aged over 90 years and a control group (302 subjects) aged less than 60 years. Results. No difference in genotype and allele frequencies of the ACE gene insertion/deletion polymorphism was observed between the longevity group and the control group. When adjusting for gender, the difference between the longevity group and the control group was also not significant regarding the frequencies of the genotypes (male, p=0.994 and female, p=0.797) as well as allele frequencies (male, p=0.969 and female, p=0.884). Conclusions.No association of the ACE gene insertion/deletion polymorphism with longevity was observed in our Han Chinese population. IntroductionLongevity has always been a desire of humankind. Although human lifespan is influenced mostly by non-genetic factors, genetic factors also have an important impact on lifespan. [1][2][3] Angiotensin-converting enzyme (ACE) cleaves angiotensin I to yield the octapeptide angiotensin II, which is a potent vasoconstrictor. 4 An Alu insertion/deletion (I/D) in intron 16 of the ACE gene has been suggested to be involved in cardiovascular disease.5 Subjects bearing the D allele have higher circulating and tissue ACE levels than those with the I allele, and homozygosity of the ACE D allele has been linked to an increased risk for myocardial infarction, left ventricular hypertrophy and in-stent restenosis after angioplasty. 6A potential role of the ACE gene I/D polymorphism in longevity was proposed in a casecontrol study in French centenarians in 1994. In an Italian population and a Korean population, studies in centenarians have also shown no association of the ACE gene I/D polymorphism with longevity. 9,10 Another study in an Italian sample reported a role of gender in the association of the ACE gene I/D polymorphism with longevity.11 In China, data from an Uighur longevity group supported the association between the ACE gene I/D polymorphism and longevity. 12,13 Han is the most populous ethnic group in China. However, little information on ACE I/D genotypes has been obtained in Han Chinese longevity populations. In this study, we examined the distribution of ACE I/D genotype and allele frequencies in two groups: a longevity group aged over 90 years and a control group aged less than 60 years living in the Dujiang Weirs area, in Southwest China, and the association of the ACE gene I/D polymorphism with longevity was evaluated. Materials and methods Study samplesWe included 701 subjects in this study. The longevity group included 399 nonagenarians an...

Is the ACE I/D polymorphism associated with extreme longevity? A study on a Spanish cohort

“…On the other hand, our study has some strengths. Similarly to other studies in this area, 16 we performed a second PCR to avoid a misclassification of ID heterozygotes as DD homozygotes. With regards to this, re-genotyping in 2001 of the samples from the pioneer study showing higher frequency of the D allele in French centenarians 6 revealed a 5% difference with the original data.…”

“…However, the association between the D allele and increased longevity has not been replicated in other studies on centenarians from Denmark, 11 France, 12 Italy, 13,14 Korea 15 or China (Han population). 16 To further complicate the issue, Forero et al 17 recently reported an age-related decrease of the D allele in a Latin-American population (Colombia). Controversy between studies can arise from different factors, including homogeneity of cohorts within a given report or geographic differences between studies.…”

Ideal lipid profile and genes for an extended life span

“…In contrast, other authors [71] found that the frequency rate of the D allele in the group of centenarians was significantly higher than that of the group aged 65-70 years, and the frequency rates of genotype DD were significantly higher in the centenarian group than in the controls. Yang et al [72] reported no association of the ACE gene polymorphism with longevity in Han Chinese individuals aged over 90 years. Also, Nacmias et al [73] did not find any involvement of the D allele in longevity.…”

Evidence from case–control and longitudinal studies supports associations of genetic variation in APOE, CETP, and IL6 with human longevity

“…These studies include rs2542052 in APOC3 (Novelli et al 2008), rs5882 in CETP (Cellini et al 2005;Novelli et al 2008), I/D insertion/deletion in ACE (Agerholm-Larsen et al 1997;Bladbjerg et al 1999;Blanche et al 2001;Yang et al 2009), rs1800562 in HFE (Carru et al 2003;Coppin et al 2003), and rs180113 in MTHFR (Bladbjerg et al 1999;Khabour et al 2009;Hessner et al 2001;Brattstrom et al 1998) and−176C/G in IL6 (Pes et al 2004;Wang et al 2001). Furthermore, a few meta-analyses or pooled analyses have been published; for APOE ε4 and the ACE I/D, insertion/deletion association was supported (McKay et al 2011;Zajc et al 2012), while for the IL6 −176C/G polymorphism, a North/South European gradient of association was suggested (Di Bona et al 2009).…”