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Candidate gene polymorphisms for diabetes mellitus, cardiovascular disease and cancer are associated with longevity in Koreans.

ABSTRACT: Long-lived people may have a unique genetic makeup that makes them more resistant than the general population to prevalent age-related diseases; however, not much is known about genes involved in the longevity. To identify susceptibility variants controlling longevity, we performed a high-throughput candidate gene study using 137 Koreans over 90 yr old and 213 young healthy Koreans. We evaluated 463 informative markers located in 176 candidate genes mostly for diabetes mellitus, cardiovascular disease and cancer under five genetic models. We estimated the odds ratios for each allele, genotype, haplotype, and gene-gene interaction using logistic regression analysis. Associations between 13 genes and longevity were detected at a P-value less than 0.01. Particularly, the rs671 (A) allele of the aldehyde dehydrogenase 2 family (mitochondrial) (ALDH2) gene was associated with longevity only in men (OR 2.11, P =0.008). Four genes, proprotein convertase subtilisin/kexin type 1 (PCSK1, P=0.008), epidermal growth factor receptor (EGFR, P=0.003), paired box 4 (PAX4, P=0.008), and V-yes-1 Yamaguchi sarcoma viral related oncogene homolog (LYN, P=0.002) consistently yielded statistical evidence for association with longevity. The findings of the current study may provide a starting point for future studies to unravel genetic factors controlling longevity in Koreans.

SUBMITTER: Park JW

PROVIDER: S-EPMC2788731 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

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Candidate gene polymorphisms for diabetes mellitus, cardiovascular disease and cancer are associated with longevity in Koreans.

Park Ji Wan JW Ji Yong Ick YI Choi Yoon Ho YH Kang Mi Yeon MY Jung Eunhyun E Cho Se Young SY Cho Hee-Youn HY Kang Byung Kyu BK Joung Yoo Sook YS Kim Duk-Hwan DH Park Sang Chul SC Park Joobae J

Experimental & molecular medicine 20091101 11

Long-lived people may have a unique genetic makeup that makes them more resistant than the general population to prevalent age-related diseases; however, not much is known about genes involved in the longevity. To identify susceptibility variants controlling longevity, we performed a high-throughput candidate gene study using 137 Koreans over 90 yr old and 213 young healthy Koreans. We evaluated 463 informative markers located in 176 candidate genes mostly for diabetes mellitus, cardiovascular d ...[more]

PMID: 19641380

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Project description:BACKGROUND:Type 2 diabetes mellitus (T2D), rapidly increasing to epidemic proportions, globally escalates cardiovascular disease risk. Although intensive interventions and comprehensive management of environmental risks factors for T2D are associated with reduced cardiovascular disease, such approaches are limited for individuals with high genetic T2D risk. In this study we investigated possible associations of ACE2 polymorphisms and cardiovascular risks in Uygur patients with T2D. METHODS:275 Uygur T2D patients and 272 non-diabetic Uygur individuals were enrolled as study participants. 14 ACE2 polymorphisms were genotyped by Matrix-assisted laser desorption ionization time-of-flight mass spectrometry. RESULTS:ACE2 SNP rs1978124, rs2048683, rs2074192, rs233575, rs4240157, rs4646156, rs4646188 and rs879922 were associated with T2D (all P?<?0.05). The 8 diabetic risk related ACE2 SNPs were further associated with diabetic related cardiovascular complications or events but exhibited heterogeneity as fellows: firstly, almost all diabetic risk related ACE2 SNPs (all P?<?0.05) were associated with increased SBP except rs1978124 and rs2074192, while rs2074192, rs4646188 and rs879922 were associated elevated DBP (all P?<?0.05). Secondly, SNP rs4646188 was not correlated with any type of dyslipidemia (TRIG, HDL-C, LDL-C or CHOL), and the other 7 diabetic risk related loci were at least correlated with one type of dyslipidemia (all P?<?0.05). In particular, rs879922 were simultaneously correlated with four type of dyslipidemia (all P?<?0.05). Thirdly, ACE2 SNP rs2074192 and rs879922 were associated with carotid arteriosclerosis stenosis (CAS)???50% (both P?<?0.05). Fourthly, ACE2 SNP rs2074192, rs4240157, rs4646188 and 879922 were associated with increased MAU (all P?<?0.05). In addition, ACE2 SNP rs2048683, rs4240157, rs4646156, rs4646188 and rs879922 were linked to heavier LVMI (all P?<?0.05), but only rs4240157, rs4646156 and rs4646188 were associated with lower LVEF (all P?<?0.05). CONCLUSION:ACE2 SNP rs879922 may be a common genetic loci and optimal genetic susceptibility marker for T2D and T2D related cardiovascular risks in Uygurs.

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Candidate gene polymorphisms for diabetes mellitus, cardiovascular disease and cancer are associated with longevity in Koreans.

Publications

Candidate gene polymorphisms for diabetes mellitus, cardiovascular disease and cancer are associated with longevity in Koreans.

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