Genotypic Effect of ABCG1 gene promoter -257T>G polymorphism on coronary artery disease severity in Japanese men.
OBJECTIVE
ATP-binding cassette transporter G1 (ABCG1) is a cholesterol transporter that plays a role in cholesterol efflux in the presence of high-density lipoprotein (HDL). Moreover, HDL-mediated cholesterol efflux is increased in cultured ABCG1 overexpressed cells; however, the physiological roles of ABCG1 and its contribution to atherosclerosis in humans remain unclear.


METHODS
The effect of ABCG1 -257T>G mutation on transcription activity was determined by a reporter assay. One hundred nine Japanese men with coronary artery disease (CAD) were analyzed. ABCG1 -257T>G polymorphism was assessed by mutation-selective PCR methods to identify T/T, T/G, and G/G genotypes.


RESULTS
The reporter assay showed that ABCG1 transcription activity was significantly lower (p<0.01) in the G allele of -257T>G polymorphism compared with that in the T allele. Clinically, there were no significant differences in serum triglyceride and total, LDL, and HDL cholesterol levels, or other risk factors. Logistic regression analysis revealed significant additive and dominant effects on the frequency of patients with multi-vessel disease compared with single-vessel disease (T/T vs. T/G vs. G/G, odds ratio:2.1, p=0.027; T/T vs. T/G and. G/G, odds ratio:3.5, p=0.005).


CONCLUSIONS
This is the first report to show that a novel ABCG1 -257T>G promoter polymorphism influences CAD severity in Japanese men.
Furuyama
Shoudai
S
Department of Cardiology, Fukuoka University Faculty of Medicine, Fukuoka 814-0180, Japan.
Uehara
Yoshinari
Y
Zhang
Bo
B
Baba
Yasuhiko
Y
Abe
Satomi
S
Iwamoto
Takahiro
T
Miura
Shin-Ichiro
S
Saku
Keijiro
K
D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000368:Aged; D003324:Coronary Artery Disease / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D016297:Mutagenesis, Site-Directed; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014158:Transcription, Genetic
C419353:ABCG1 protein, human; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters