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The rs1333049 polymorphism on locus 9p21.3 and extreme longevity in Spanish and Japanese cohorts.

ABSTRACT: The rs1333049 (G/C) polymorphism located on chromosome 9p21.3 is a candidate to influence extreme longevity owing to its association with age-related diseases, notably coronary artery disease (CAD). We compared allele/genotype distributions of rs1333049 in cases (centenarians) and controls (younger adults, without (healthy) or with CAD) in two independent cohorts: Spanish (centenarians: n?=?152, 128 women, 100-111 years; healthy controls: n?=?343, 212 women, age <50 years; CAD controls: n?=?98, 32 women, age ?65 years) and Japanese (centenarians: n?=?742, 623 women, 100-115 years; healthy controls: n?=?920, 511 women, < 60 years; CAD controls: n?=?395, 45 women, age ?65 years). The frequency of the "risk" C-allele tended to be lower in Spanish centenarians (47.0 %) than in their healthy (52.9 %, P?=?0.088) or CAD controls (55.1 %, P?=?0.078), and significant differences were found in genotype distributions (P?=?0.034 and P?=?0.045), with a higher frequency of the GG genotype in cases than in both healthy and CAD controls as well as a lower proportion of the CG genotype compared with healthy controls. In the Japanese cohort, the main finding was that the frequency of the C-allele did not differ between centenarians (46.4 %) and healthy controls (47.3 %, P?=?0.602), but it was significantly lower in the former than in CAD controls (57.2 %, P?

SUBMITTER: Pinos T

PROVIDER: S-EPMC4039251 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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The rs1333049 polymorphism on locus 9p21.3 and extreme longevity in Spanish and Japanese cohorts.

Pinós Tomàs T Fuku Noriyuki N Cámara Yolanda Y Arai Yasumichi Y Abe Yukiko Y Rodríguez-Romo Gabriel G Garatachea Nuria N Santos-Lozano Alejandro A Miro-Casas Elisabet E Ruiz-Meana Marisol M Otaegui Imanol I Murakami Haruka H Miyachi Motohiko M Garcia-Dorado David D Hinohara Kunihiko K Andreu Antoni L AL Kimura Akinori A Hirose Nobuyoshi N Lucia Alejandro A Lucia Alejandro A

Age (Dordrecht, Netherlands) 20131028 2

The rs1333049 (G/C) polymorphism located on chromosome 9p21.3 is a candidate to influence extreme longevity owing to its association with age-related diseases, notably coronary artery disease (CAD). We compared allele/genotype distributions of rs1333049 in cases (centenarians) and controls (younger adults, without (healthy) or with CAD) in two independent cohorts: Spanish (centenarians: n = 152, 128 women, 100-111 years; healthy controls: n = 343, 212 women, age <50 years; CAD controls: n = 98, ...[more]

PMID: 24163049

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Project description:ObjectiveThe rs10757278, rs1333049 and rs4977574 are single nucleotide polymorphisms (SNPs) of chromosome 9p21 locus associated with a prevalence of acute coronary syndromes (ACS). Reports concerning their association with long-term outcome after an ACS are equivocal. The aim of our study was to investigate the association of the 9p21.3 locus with 5-year overall mortality in patients with ST-elevation myocardial infarction (STEMI).Materials and methodsWe performed a retrospective analysis of data collected prospectively in 2 independent registries of consecutive patients with STEMI (derivation and validation group). Genotyping was performed with the TaqMan method. The analyzed end-point was total mortality.ResultsThe derivation group comprised 589 patients: 25.3% female (n = 149), mean age 62.4 ± 12.0 years, total 5-year mortality 16.6% (n = 98). When all the study group was analyzed, no significant differences in mortality were found between the genotypes. However, in high-risk patients (GRACE risk score ? 155 points, n = 238), homozygotes associated with higher risk for ACS had significantly better 5-year survival compared to other genotypes. The hazard ratio associated with the high-risk genotype (a homozygote of high risk for ACS or a heterozygote) was: HR = 2.2 (1.15-4.2) for the rs10757278 polymorphism, HR = 2.7 (95% CI 1.3-5.4) for the rs4977574 one and HR = 2.3 (1.2-4.5) for the rs1333049 one (Cox proportional hazards model). Survival analysis in the validation group (n = 365) showed a clear trend towards better prognosis in GG homozygotes of the rs10757278 SNP, which confirms our initial results (p = 0.09, log-rank test).ConclusionsThe 9p21.3 locus is associated with 5-year mortality in high-risk patients with STEMI. The genotypes associated with higher risk for ACS show a protective effect in terms of further survival (instead of a deteriorating prognosis, as reported previously). This finding, due to the very high size of the effect, could potentially be applied to clinical practice, if appropriate methods are elaborated.

Project description:BackgroundIncreased arterial stiffness is a cardiovascular outcome of metabolic syndrome (MetS). The chromosome 9p21 locus has been identified as a major locus for risk of coronary artery disease (CAD). The single nucleotide polymorphism (SNP), rs1333049 on chromosome 9p21.3 has been strongly associated with CAD and myocardial infarction. Increased arterial stiffness could be the link between the 9p21 polymorphism and increased cardiovascular risk. Since the impact of a genetic polymorphism on arterial stiffness especially in Asian populations has not been well defined, we aimed to investigate the association of arterial stiffness with rs 1333049 variant on chromosome 9p21.3 in Thai subjects with and without MetS risk factors.MethodsA total of 208 Thai subjects, aged 35-75 years, 135 with and 73 without MetS, according to IDF and NCEP-ATPIII criteria, were included in this study. Aortic-femoral pulse wave velocity (afPWV), brachial-ankle pulse wave velocity (baPWV) and aortic ankle pulse wave velocity (aaPWV) were measured and used as markers of arterial stiffness. The chromosome 9p21.3 locus, represented by the rs 1333049 variant and blood biochemistry were evaluated.ResultsArterial stiffness was elevated in subjects with MetS when compared with nonMetS subjects. PWV, especially afPWV increased progressively with increasing number of MetS risk factors (r = 0.322, P <0.001). We also found that the frequency distribution of the rs1333049 genotypes is significantly associated with the afPWV (P <0.05). In multivariate analyses, there was an association between homozygous C allele and afPWV (Odds ratio (OR), 8.16; 95% confidence interval (CI), 1.91 to 34.90; P = 0.005), while the GC genotype was not related to afPWV (OR, 1.79; 95% CI, 0.84 to 3.77; P = 0.129) when compared with the GG genotype.ConclusionsOur findings demonstrate for the first time that arterial stiffness is associated with genetic polymorphism in 9p21 and metabolic risk factors in a Thai population.

Dataset Information

The rs1333049 polymorphism on locus 9p21.3 and extreme longevity in Spanish and Japanese cohorts.

Publications

The rs1333049 polymorphism on locus 9p21.3 and extreme longevity in Spanish and Japanese cohorts.

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