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.

ABCG5/G8 polymorphisms and markers of cholesterol metabolism: systematic review and meta-analysis

“…15 ). Several studies showed positive associations with plasma lipoprotein levels ( 5,7,8 ), which we and others were not able to replicate. The majority of these studies were small-scaled.…”

“…In addition, due to their skewed distribution, triglyceride data could not be pooled. Twelve studies reported signifi cant associations with baseline triglyceride levels, which mostly involved the p.T400K polymorphism ( 13,29,33 ); however, this was not consistent throughout all included studies ( 8,11,12,27,(30)(31)(32). Finally, in our analyses, we assumed a dominant genetic model, as most of the included studies presented their data according to this model.…”

“…The number of study participants ranged from 26 to 1,046. Five studies were conducted in a population of Caucasians ( 5,7,11,13,27 ), three studies investigated Asian populations ( 8,28,29 ), two studies were conducted in a Hispanic population ( 30 ), and two in a mixed racial population ( 31,32 ). The remaining three studies did not report the ethnicity of the study subjects ( 9,12,33 ).…”

“…The majority of the studies were conducted in mildly hypercholesterolaemic, otherwise healthy populations ( 5,12,13,27,28,(31)(32)(33). Five studies evaluated normocholesterolaemic subjects ( 9,11,29,30 ); two studies evaluated both ( 8,30 ). Most studies included normoweighted subjects; however, one study selected overweight, mildly hypercholesterolaemic women ( 31 ), and one study was conducted in obese, insulin-resistant men without type 2 diabetes mellitus (T2DM) ( 33 ).…”

The ABCG5 ABCG8 sterol transporter and phytosterols: implications for cardiometabolic disease

“…The D19H polymorphism has been positively associated with the risk of cholesterol gallstones in three independent studies using multiple ethnicities [24-26]. In a few studies, plasma levels of plant sterols were inversely related to BMI and markers of insulin resistance [27]. However, phytosterol supplementation had no beneficial effect on the development of obesity and insulin resistance in a high-fat diet model of obesity in mice [28].…”