Candidate gene polymorphisms for diabetes mellitus, cardiovascular disease and cancer are associated with longevity in Koreans.
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.
Park
Ji Wan
JW
Department of Medical Genetics, Hallym University College of Medicine, Chuncheon 200-702, Korea.
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
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000444:Aldehyde Dehydrogenase / Q000235:genetics; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000483:Alleles; D044466:Asian People / Q000208:ethnology / Q000235:genetics; D002318:Cardiovascular Diseases / Q000208:ethnology / Q000235:genetics*; D003920:Diabetes Mellitus / Q000208:ethnology / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D006239:Haplotypes; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007723:Korea; D008136:Longevity / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000208:ethnology / Q000235:genetics*; D051761:Paired Box Transcription Factors / Q000235:genetics; D011110:Polymorphism, Genetic; D045664:Proprotein Convertase 1 / Q000235:genetics; D012737:Sex Factors; D019061:src-Family Kinases / Q000235:genetics
D005819:Genetic Markers; D018398:Homeodomain Proteins; C491709:PAX4 protein, human; D051761:Paired Box Transcription Factors; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; C512478:EGFR protein, human; D066246:ErbB Receptors; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D045664:Proprotein Convertase 1