Association of a polymorphic variant of the Werner helicase gene with myocardial infarction in a Japanese population.
The Werner syndrome (WS) is a rare autosomal recessive progeroid syndrome characterized by the premature onset of multiple age-related disorders, including atherosclerosis, cancer, non-insulin-dependent diabetes mellitus (NIDDM), ocular cataracts and osteoporosis [Epstein et al., 1966]. The major cause of death (at a median age of 47) is myocardial infarction (MI) [Epstein et al., 1966]. The WS mutation involves a member (WRN) of the RecQ family of helicases and may perturb DNA replication, repair, recombination, transcription, or chromosomal segregation [Yu et al., 1996]. We now report data on 149 MI cases and age-matched controls suggesting that a polymorphic WRN variant is associated with increased risk for MI. Based on our data, homozygosity for a cysteine at amino acid 1367 (the most prevalent genotype) predicts a 2.78 times greater risk of MI (95% confidence intervals: 1.23 to 6.86). The variant was not significantly associated with NIDDM. The two alleles (cysteine vs. arginine) could influence helicase activity, turnover, macromolecular interactions or, alternatively, could be markers for haplotypes influencing WRN regulation or reflecting gene action at linked loci. However, given the caveats implicit in genetic association studies, it is imperative that the present results be replicated in independent populations.
Ye
L
L
Department of Geriatric Medicine, Osaka University Medical School, Japan.
Miki
T
T
Nakura
J
J
Oshima
J
J
Kamino
K
K
Rakugi
H
H
Ikegami
H
H
Higaki
J
J
Edland
S D
SD
Martin
G M
GM
Ogihara
T
T
D000328:Adult; D017668:Age of Onset; D000368:Aged; D001120:Arginine / Q000235:genetics; D016022:Case-Control Studies; D003545:Cysteine / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D006720:Homozygote; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009203:Myocardial Infarction / Q000453:epidemiology / Q000235:genetics*; D011110:Polymorphism, Genetic; D014898:Werner Syndrome / Q000453:epidemiology* / Q000235:genetics*
D001120:Arginine; D003545:Cysteine