ATP-binding cassette transporter G8 M429V polymorphism as a novel genetic marker of higher cholesterol absorption in hypercholesterolaemic Japanese subjects

Miwa, Kenji; Inazu, Akihiro; Kobayashi, Junji; Higashikata, Toshinori; Nohara, Atsushi; Kawashiri, Masa‐aki; Katsuda, Shoji; Takata, Munehisa; Koizumi, Junji; Mabuchi, Hiroshi

doi:10.1042/cs20050030

Cited by 46 publications

(36 citation statements)

References 25 publications

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“…They concluded that women carriers of GG genotype showed stables levels of cholesterol and non response to dietary changes; however, carriers of AA genotype had a mayor reduction in plasma cholesterol between 1988 and 1996. On the other hand, our results for this polymorphism differ with Miwa et al (2005) who did not find any association with this genetic variant and lipid levels in patients from Japan. Similarly, Wang et al (2007) did not find significant differences in plasma and biliary lipid levels.…”

Section: Discussioncontrasting

confidence: 55%

Effect of Five Single Nucleotide Polymorphisms of ABCG5 and ABCG8 Genes on Ezetimibe Lipid-Lowering Response

Caamaño¹,

Saavedra²,

Zambrano³

et al. 2012

Int. J. Morphol.

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SUMMARY:In this study we evaluated the possible association between five single nucleotide polymorphisms in ABCG5 (rs6720173) and ABCG8 (rs11887534, rs4148211, rs4148217 and rs6544718) genes and ezetimibe response in Chilean hypercholesterolemic subjects. A total of 60 non-related hypercholesterolemic subjects, aged 18 to 65 years old were included in this study. These subjects were treated with ezetimibe (10mg/day) during one month. The ABCG5 and ABCG8 genotypes were assessed by PCR-RFLP. The genotype distribution of the ABCG5/ABCG8 polymorphisms was in Hardy-Weinberg equilibrium. Our results showed that the investigated polymorphisms were not associated with the response to ezetimibe. Nevertheless, the T allele of rs6544718 polymorphism was related to higher baseline levels of LDL-cholesterol (p<0.001). In addition, the G allele for the rs4148211 polymorphism was associated with greater baseline concentrations of triglycerides (P=0.019). This allele was also associated with lower concentrations of HDL-cholesterol (P=0.027), after ezetimibe treatment. Our results suggest that the studied polymorphisms do not affect the therapeutic response to ezetimibe in the evaluated subjects.

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Section: Discussioncontrasting

confidence: 55%

Effect of Five Single Nucleotide Polymorphisms of ABCG5 and ABCG8 Genes on Ezetimibe Lipid-Lowering Response

Caamaño¹,

Saavedra²,

Zambrano³

et al. 2012

Int. J. Morphol.

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“…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 ).…”

Section: Meta-analysis: Characteristics Of Included Studiesmentioning

confidence: 99%

“…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 ).…”

Section: Meta-analysis: Characteristics Of Included Studiesmentioning

confidence: 99%

“…Six studies evaluated associations between ABCG5/G8 polymorphisms and non-cholesterol sterol concentrations ( 5,11,13,28,33 ). Analysis of the pooled data revealed that the minor allele of the p.D19H variant was associated with signifi cantly reduced markers of cholesterol absorption and increased markers of cholesterol synthesis ( Fig.…”

Section: Meta-analysis: Pooled Effects Of Polymorphisms On Lipids Andmentioning

confidence: 99%

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

Jakulj

Vissers

Tanck

et al. 2010

Journal of Lipid Research

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This article is available online at http://www.jlr.org cated at the intestinal brush border membrane. In fact, cholesterol and plant sterols are taken up by the enterocyte through the Niemann-Pick C1 Like 1 (NPC1L1) transporter ( 1 ). The ATP-binding cassette (ABC) transporters G5 and G8 actively effl ux plant sterols and, to lesser extent cholesterol, back into the intestinal lumen. In addition, ABCG5 and ABCG8 are located at the canalicular membranes of hepatocytes, where they facilitate effl ux of cholesterol and plant sterols into bile ( 2 ).The ABCG5 and ABCG8 genes are located in a headto-head confi guration on chromosome 2p21 ( 3 ). Mutations in either of these genes can cause sitosterolemia, a rare autosomal, recessively inherited disorder, characterized by xanthomas, arthralgia, anemia, and premature atherosclerosis ( 3 ). The underlying mechanism involves increased intestinal absorption of plant sterols and concomitantly decreased biliary secretion of sterols due to the absence of a functional ABCG5/G8 transporter protein ( 4 ). In addition to rare sequence changes causing sitosterolemia, several more common sequence variants in ABCG5/G8 were identifi ed in both healthy and hypercholesterolaemic individuals. These single nucleotide polymorphisms (SNP) were found to be associated with plasma cholesterol and noncholesterol sterol levels ( 5-8 ), as well as with the response to various cholesterol-lowering strategies, including diet interventions ( 7, 9 ), consumption of plant sterols or stanols ( 10, 11 ), and treatment with statins ( 12 ).Abstract Genetic variation at the ABCG5/G8 locus has been associated with markers of cholesterol homeostasis. As data originate from small-scale studies, we performed a meta-analysis to study these associations in a large dataset. We fi rst investigated associations between fi ve common ABCG5/G8 polymorphisms (p.Q604E, p.D19H, p.Y54C, p. T400K, and p.A632V) and plasma sterol levels in 245 hypercholesterolaemic individuals. No signifi cant associations were found. Subsequently, our data were pooled into a meta-analysis that comprised 3,364 subjects from 16 studies Intestinal cholesterol absorption is an active and selective process, mediated by several transporter proteins lo-

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“…This has been associated with premature coronary atherosclerosis and death (Hubá-ček et al 2001). Common sequence variations in the ABCG5 and ABCG8 genes have been reported to account for the variability in cholesterol and phytosterol absorption Plat et al 2005;Hubáček et al 2004;Miwa et al 2005;Weggemans et al 2002). Although a clear link has been established between ABCG5/ABCG8 genes and modification of the absorption and/or synthesis of plant sterols, there is still no consensus on the association of plasma total cholesterol and ABCG5/ABCG8 gene polymorphisms (Sehayek et al 2004;Berge et al 2002).…”

Section: Introductionmentioning

confidence: 99%

Significant association of ABCG8:D19H gene polymorphism with hypercholesterolemia and insulin resistance

et al. 2008

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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.

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ATP-binding cassette transporter G8 M429V polymorphism as a novel genetic marker of higher cholesterol absorption in hypercholesterolaemic Japanese subjects

Cited by 46 publications

References 25 publications

Effect of Five Single Nucleotide Polymorphisms of ABCG5 and ABCG8 Genes on Ezetimibe Lipid-Lowering Response

Effect of Five Single Nucleotide Polymorphisms of ABCG5 and ABCG8 Genes on Ezetimibe Lipid-Lowering Response

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

Significant association of ABCG8:D19H gene polymorphism with hypercholesterolemia and insulin resistance

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