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.
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