Frequencies of four ATP-binding cassette transporter G8 polymorphisms in patients with ischemic vascular diseases

ATP-binding cassette transporter G8 (ABCG8) was found to participate in plant sterol and cholesterol (CHOL) transport; however, the potential associations of ABCG8 genetic variants and ischemic vascular diseases are largely unknown. Determinations of allele frequencies of four common ABCG8 polymorphisms (D19H, Y54C, T400K, and A632V) were carried out in 241 unrelated patients with ischemic stroke, 148 patients with coronary heart disease, and 191 blood donors (controls). Allele frequencies of the investigated polymorphisms in patient groups showed no significant differences compared with controls. There was a tendency toward reduced 54YY-genotype frequency among male patients with stroke. On stratification by age at disease onset, male patients with stroke under the age of 50 (n = 62) showed significantly reduced 54YY-frequency compared with male controls (n = 92; 24.2% vs. 41.3%; odds ratio: 0.45 [95% confidence intervals: 0.22-0.93]; p = 0.038). No such associations were found among women. In healthy controls, CHOL levels of individuals with the 54YY genotype (n = 71; median: 4.51 mM, 25th-75th percentiles: 4.19-5.43) were significantly reduced compared with 54YC and 54CC individuals combined (n = 120; median: 4.95 mM, 25th-75th percentiles: 4.42-5.88, p = 0.009). Further, we identified a new ABCG8-variant, T401S, in a control subject. In conclusion, ABCG8 54YY-genotype may be a potential protecting factor against ischemic stroke in young men and may influence plasma CHOL levels.