title: Significant association of ABCG8:D19H gene polymorphism with hypercholesterolemia and insulin resistance.
abstract: The absorption efficiency of cholesterol is closely correlated to dietary phytosterol content and determined by genetic factors. The ATP-binding cassette (ABC) transporters ABCG5 and ABCG8 act as a sterol efflux pump to regulate the absorption of cholesterol and phytosterol. The levels of cholesterol and phytosterol associated with a Chinese diet are very different from those associated with a Western diet. This study aims to explore the association between serum total cholesterol/LDL-C levels and ABCG5/ABCG8 polymorphisms in a Taiwanese population consuming an ordinary Chinese diet. A total of 1,046 subjects (894 men and 152 women) were recruited in a hospital-based health check-up center in Kaohsiung Medical University Hospital. Five nonsynonymous polymorphisms of Q604E (ABCG5), D19H, C54Y, T400 K and A632 V (ABCG8) were analyzed by TaqMan genotyping assay. Analysis showed that the D19H polymorphism of the ABCG8 gene was significantly associated with serum total cholesterol, LDL-C levels and HOMA-IR index. Adjusting for sex and age, subjects with the D19H (GC) genotype were significantly associated with a threefold higher risk of high cholesterol and LDL-C levels than subjects with D19 (GG). These results suggest that the D19H polymorphism of ABCG8 could be considered a susceptible gene marker indicating an increased likelihood of developing high cholesterol and LDL-C levels in Taiwanese consuming an ordinary Chinese diet. It is supposed that the coexistence of higher insulin resistance and hypercholesterolemia for carriers of the D19H polymorphism may result in a greater risk of cardiovascular disease.
authors.affiliation: Division of Cardiology and General Medicine, Chi-Mei Medical Center, Chung Hwa University of Medical Technology, Tainan, Taiwan.
authors.forename: Zhih-Cherng
authors.initials: ZC
authors.lastname: Chen
authors.affiliation: Division of Endocrinology and Metabolism, Internal Medicine, Kaohsiung Medical University, 100 Tzyou 1st Rd, Kaohsiung, 807, Taiwan.
authors.forename: Shyi-Jang
authors.initials: SJ
authors.lastname: Shin
authors.affiliation: Hepatobiliary Division, Department of Surgery, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Kung-Kai
authors.initials: KK
authors.lastname: Kuo
authors.affiliation: Division of Endocrinology and Metabolism, Internal Medicine, Kaohsiung Medical University, 100 Tzyou 1st Rd, Kaohsiung, 807, Taiwan.
authors.forename: Kun-Der
authors.initials: KD
authors.lastname: Lin
authors.affiliation: Department of Preventive Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Ming-Lung
authors.initials: ML
authors.lastname: Yu
authors.affiliation: Division of Endocrinology and Metabolism, Internal Medicine, Kaohsiung Medical University, 100 Tzyou 1st Rd, Kaohsiung, 807, Taiwan. pjhsiao@cc.kmu.edu.tw.
authors.forename: Pi-Jung
authors.initials: PJ
authors.lastname: Hsiao
mesh_terms: D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution / Q000235:genetics*; D001224:Aspartic Acid / Q000235:genetics; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D006639:Histidine / Q000235:genetics; D006801:Humans; D006937:Hypercholesterolemia / Q000235:genetics*; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: C416946:ABCG8 protein, human; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters; D008078:Cholesterol, LDL; D001224:Aspartic Acid; D006639:Histidine