Interaction between Cholesteryl Ester Transfer Protein and Hepatic Lipase Encoding Genes and the Risk of Type 2 Diabetes: Results from the Telde Study

Abstract

Background and AimDiabetic dyslipidaemia is common in type 2 diabetes (T2D) and insulin resistance and often precedes the onset of T2D. The Taq1B polymorphism in CETP (B1 and B2 alleles) (rs708272) and the G-250A polymorphism in LIPC (rs2070895) are associated with changes in enzyme activity and lipid concentrations. Our aim was to assess the effects of both polymorphisms on the risk of T2D.Methods and ResultsIn a case-control study from the population-based Telde cohort, both polymorphisms were analysed by PCR-based methods. Subjects were classified, according to an oral glucose tolerance test, into diabetic (N = 115) and pre-diabetic (N = 116); 226 subjects with normal glucose tolerance, matched for age and gender, were included as controls. Chi-square (comparison between groups) and logistic regression (identification of independent effects) were used for analysis. The B1B1 Taq1B CETP genotype frequency increased with worsening glucose metabolism (42.5%, 46.1% and 54.3% in control, IGR and diabetic group; p = 0.042). This polymorphism was independently associated with an increased risk of diabetes (OR: 1.828; IC 95%: 1.12–2.99; p = 0.016), even after adjusting by confounding variables, whereas the LIPC polymorphism was not. Regarding the interaction between both polymorphisms, in the B1B1 genotype carriers, the absence of the minor (A) allele of the LIPC polymorphism increased the risk of having diabetes.ConclusionThe presence of the B1B1 Taq1B CETP genotype contributes to the presence of diabetes, independently of age, sex, BMI and waist. However, among carriers of B1B1, the presence of GG genotype of the -250 LIPC polymorphism increases this risk further.

Taq1B CETP Polymorphism and Cardiovascular Risk in an Endogamous Pop-ulation of Diabetic Men: A Study in Santa Rosa Del Conlara, San Luis, Argentina

“…These findings agree with the association between HDL-c concentrations and Taq1B polymorphism of the CETP gene in the Veterans Affairs HDL-c Intervention Trial [13]. However, men who have the B1 allele may be at increased risk for metabolic complications due to the larger central adiposity and altered distribution of cholesteryl esthers (CE) and TG [38]- [40]. The cholesterol exchange process from HDL to non-HDL lipoproteins is mediated by CETP that facilitates the incorporation of CE into TG-rich lipoproteins as part of the reverse cholesterol transport pathway [5].…”

Assessment of established HDL-C loci for association with HDL-C levels and type 2 diabetes in Pima Indians

“…Since the female sex-specific association of rs6499863 with type 2 diabetes does not achieve genome-wide significance, and CETP has not been identified as a type 2 diabetes locus in large GWAS studies [39, 40], this hypothesis requires validation. However, the current observation is consistent with a previously identified association of the Taq1B (rs708272) polymorphism in CETP and higher plasma cholesteryl ester transfer protein (CETP) activity, HDL-C levels, HOMA-IR, metabolic syndrome and type 2 diabetes [41]. This variant associated with metabolic syndrome independent of its association with insulin resistance and HDL-C [42].…”

Missing heritability of common diseases and treatments outside the protein-coding exome

“…Epistatic interactions have been shown to contribute to quantitative traits such as gene expression and lipid levels as well as disease risk, for example in relation to diabetes and Alzheimer’s disease (Gusareva et al 2014; Hemani et al 2014; Lopez-Rios et al 2011; Ma et al 2014). Furthermore, epistasis has been proposed as one of the mechanisms to fill the heritability gap (Wang et al 2012b; Zuk et al 2012).…”