Exp Mol Med.  2009 Nov;41(11):772-781. 10.3858/emm.2009.41.11.083.

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

• Park JW
• Ji YI
• Choi YH
• Kang MY
• Jung E
• Cho SY
• Cho HY
• Kang BK
• Joung YS
• Kim DH
• Park SC
• Park J

• KMID: 1122278
• DOI: http://doi.org/10.3858/emm.2009.41.11.083

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.

Keyword

case-control studies; genome-wide association study; longevity; polymorphism, single nucleotide

MeSH Terms

Adult
Aged
Aged, 80 and over
Aldehyde Dehydrogenase/genetics
Alleles
Asian Continental Ancestry Group/ethnology/genetics
Cardiovascular Diseases/ethnology/*genetics
Diabetes Mellitus/ethnology/*genetics
Female
Genetic Markers/genetics
Haplotypes
Homeodomain Proteins/genetics
Humans
Korea
Longevity/*genetics
Male
Middle Aged
Neoplasms/ethnology/*genetics
Paired Box Transcription Factors/genetics
*Polymorphism, Genetic
Proprotein Convertase 1/genetics
Receptor, Epidermal Growth Factor/genetics
Sex Factors
src-Family Kinases/genetics