Fas promoter region gene polymorphism is associated with an increased risk for myocardial infarction.
A growing body of evidence has shown that Fas-mediated apoptosis is involved in atherosclerosis progression. Recent studies have revealed that a single nucleotide polymorphism (SNP) in the Fas promoter region (-670G/A) influences Fas expression. Here, we investigated whether -670G/A SNP influences the incidence of myocardial infarction (MI) by examining a comparison between MI patients (n=154) and control subjects (n=462) in a Japanese population. The allele frequency in each group was A 53.6%/G 46.4% in the MI patients, and A 43.9%/G 56.1% in the non-MI subjects (chi(2)=8.6; P=0.003). The odds ratio was 2.62 (95% CI: 1.43-4.88). As subjects with the -670AA genotype had a signal transducer and activator of transcription 1 (STAT1)-binding site in the Fas promoter region, STAT-1 activation by interferon-gamma may upregulate Fas expression in human vascular smooth muscle cells (VSMCs) of -670AA genotype subjects as described earlier. The Fas upregulation induces excess apoptosis to VSMCs, which leads to unstable plaque formation in atherosclerotic lesions and then potentially to plaque rupture, which can cause MI. Further investigation of hypertensive subjects revealed that the -670AA genotype does not induce hypertension occurrence, supporting that this difference of MI occurrence between the -670AA genotype and the -670GG genotype may be because of plaque rupture followed by excess apoptosis of VSMCs in the atherosclerotic lesion. We conclude that the Fas promoter gene, SNP (-670G/A), may be a risk factor of MI occurrence.
Hanasaki
Hiroko
H
Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Takemura
Yukihiro
Y
Fukuo
Keisuke
K
Ohishi
Mitsuru
M
Onishi
Miyuki
M
Yasuda
Osamu
O
Katsuya
Tomohiro
T
Awata
Nobuhisa
N
Kato
Norihiro
N
Ogihara
Toshio
T
Rakugi
Hiromi
H
D000368:Aged; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006949:Hyperlipidemias / Q000453:epidemiology; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology* / Q000235:genetics*; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012306:Risk; D050794:STAT1 Transcription Factor / Q000235:genetics; D019014:fas Receptor / Q000235:genetics*
D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D019014:fas Receptor