title: Association of Polymorphisms in Connective Tissue Growth Factor and Epidermal Growth Factor Receptor Genes With Human Longevity.
abstract: Growth pathways play key roles in longevity. The present study tested single-nucleotide polymorphisms (SNPs) in the connective tissue growth factor gene (CTGF) and the epidermal growth factor receptor gene (EGFR) for association with longevity. Comparison of allele and genotype frequencies of 12 CTGF SNPs and 41 EGFR SNPs between 440 American men of Japanese ancestry aged ≥95 years and 374 men of average life span revealed association with longevity at the p < .05 level for 2 SNPs in CTGF and 7 in EGFR. Two in CTGF and two in EGFR remained significant after Bonferroni correction. The SNPs of both CTGF and EGFR were in a haplotype block in each respective gene. Haplotype analysis confirmed the suggestive association found by χ2 analysis. We noted an excess of heterozygotes among the longevity cases, consistent with heterozygote advantage in living to extreme old age. No associations of the most significant SNPs were observed in whites or Koreans. In conclusion, the present findings indicate that genetic variation in CTGF and EGFR may contribute to the attainment of extreme old age in Japanese. More research is needed to confirm that genetic variation in CTGF and EGFR contributes to the attainment of extreme old age across human populations.
authors.affiliation: Department of Research, Honolulu Heart Program/Honolulu-Asia Aging Study (HAAS), Kuakini Medical Center, Hawaii.|Department of Cell and Molecular Biology and Department of Pathology, John A. Burns School of Medicine, University of Hawaii Manoa, Honolulu.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Donlon
authors.affiliation: Department of Research, Honolulu Heart Program/Honolulu-Asia Aging Study (HAAS), Kuakini Medical Center, Hawaii.|Basic & Clinical Genomics Laboratory, School of Medical Sciences and Bosch Institute, University of Sydney, New South Wales, Australia.|Department of Geriatric Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Morris
authors.affiliation: Department of Research, Honolulu Heart Program/Honolulu-Asia Aging Study (HAAS), Kuakini Medical Center, Hawaii.
authors.forename: Qimei
authors.initials: Q
authors.lastname: He
authors.affiliation: Department of Research, Honolulu Heart Program/Honolulu-Asia Aging Study (HAAS), Kuakini Medical Center, Hawaii.
authors.forename: Randi
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Research, Honolulu Heart Program/Honolulu-Asia Aging Study (HAAS), Kuakini Medical Center, Hawaii.|Department of Geriatric Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu.
authors.forename: Kamal H
authors.initials: KH
authors.lastname: Masaki
authors.affiliation: Institute for Biogenesis Research, John A. Burns School of Medicine, University of Hawaii Manoa, Honolulu, Hawaii.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Allsopp
authors.affiliation: Department of Research, Honolulu Heart Program/Honolulu-Asia Aging Study (HAAS), Kuakini Medical Center, Hawaii.|Department of Geriatric Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu.|Department of Human Welfare, Okinawa International University, Japan.
authors.forename: D Craig
authors.initials: DC
authors.lastname: Willcox
authors.affiliation: California Pacific Medical Center Research Institute, San Francisco.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Tranah
authors.affiliation: California Pacific Medical Center Research Institute, San Francisco.
authors.forename: Neeta
authors.initials: N
authors.lastname: Parimi
authors.affiliation: California Pacific Medical Center Research Institute, San Francisco.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Evans
authors.affiliation: Institute of Clinical Molecular Biology, Kiel University, Germany.
authors.forename: Friederike
authors.initials: F
authors.lastname: Flachsbart
authors.affiliation: Institute of Clinical Molecular Biology, Kiel University, Germany.
authors.forename: Almut
authors.initials: A
authors.lastname: Nebel
authors.affiliation: Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Duk-Hwan
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Joobae
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Research, Honolulu Heart Program/Honolulu-Asia Aging Study (HAAS), Kuakini Medical Center, Hawaii.|Department of Geriatric Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Willcox
mesh_terms: D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D055513:Connective Tissue Growth Factor / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D008136:Longevity / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D014481:United States / Q000453:epidemiology; D044465:White People / Q000235:genetics
chemical_list: C526317:CCN2 protein, human; D055513:Connective Tissue Growth Factor; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Case–control study; Connective tissue growth factor; Epidermal growth factor; Longevity; Molecular genetics