The association of ABCG5/G8 gene polymorphisms with blood lipid profile in Thais

Abstract

Cardiovascular diseases (CVDs) are the chronic diseases and the leading cause of global death and disability. Risk factors for CVD are encompassing both genetics and environmental background. ATP-binding cassette transporters G5 and G8 (ABCG5/G8) are membrane transporters that express on enterocytes and hepatocytes; they play roles in the regulation of body lipid homeostatis. Several studies have investigated the association of ABCG5/G8 gene polymorphisms on blood lipids, however, with controversial results. In addition, there are no reports regarding ABCG5/G8 gene polymorphisms in Thai population. The objective of present study was to determine the association of ABCG5/G8 gene polymorphisms and lipid profile as well as other CVD risk factors in Thais. The ABCG5 Q604E C>G, ABCG8 5U145 A>C, and ABCG8 Y54C A>G gene polymorphisms were determined using allele-specific polymerase chain reaction (ASPCR) technique. The respective major and minor alleles were: G (81.3%) and C (18.7%) for ABCG5 Q604E C>G; C (84.9%) and A (15.1%) for ABCG8 5U145 A>C; and G (78.8%) and A (21.2%) for ABCG8 Y54C A>G. The individuals with GG genotype of ABCG5 Q604E C>G showed significantly higher level of DBP and TC than C carriers. For ABCG8 5U145 A>C, subjects with CC genotype demonstrated significantly higher level of TC, LDL-C, and LDL-C/HDL-C than those with A allele. There were no statistically significant differences of either lipid levels or other CVD risk factors among genotypes of ABCG8 Y54C A>G. Association study initially demonstrated, only in male subjects,  that CC genotype of ABCG8 5U145 A>C significantly increased the risk of hypertension (OR 4.81, 95%CI: 1.45-16.02) as compared with A allele carriers (AC+AA). Further investigation for the combined effect revealed significant association of combined GG/CC genotypes of ABCG5 Q604E C>G and ABCG8 5U145 A>C with increase risk of dyslipidemia (OR 2.48, 95%CI: 1.02-6.03) compared to CG/AC, CG/AA, CC/CC, CC/AC, and CC/AA genotypes, however only in female subjects. This is the first report regarding the study of ABCG5/G8 gene polymorphisms in Thais. The present results demonstrate the associations of ABCG5/G8 gene polymorphisms with abnormal lipid profile and hypertension, and provide as preliminary information for more comprehensive study with the ultimate aim for CVD prevention campaign.