Variant rs10911021 that associates with coronary heart disease in type 2 diabetes, is associated with lower concentrations of circulating HDL cholesterol and large HDL particles but not with amino acids. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Beaney, Katherine; Cooper, Jackie; McLachlan, Stela; Wannamethee, S.; Jefferis, Barbara; Whincup, Peter; Ben-Shlomo, Yoav; Price, Jacqueline; Kumari, Meena; Wong, Andrew; Ong, Ken; Hardy, Rebecca; Kuh, Diana; Kivimaki, Mika; Kangas, Antti; Soininen, Pasi; Ala-Korpela, Mika; Drenos, Fotios; Humphries, Steve
• Is Part Of: Cardiovascular diabetology. Volume 15:Issue 1(2016)
• Page Start: 1
• Page End: 11
• Publication Date: 2016-12
• Subjects: Coronary heart disease -- Metabolomics -- HDL-cholesterol -- Genetic risk; Diabetes -- Complications -- Periodicals; Cardiovascular system -- Diseases -- Complications -- Periodicals; Cardiovascular system -- Diseases -- Prevention -- Periodicals; 616.462
• DOI: 10.1186/s12933-016-0435-0
• Languages: English
• ISSNs: 1475-2840

Abstract

Abstract Aims An intergenic locus on chromosome 1 (lead SNP rs10911021) was previously associated with coronary heart disease (CHD) in type 2 diabetes (T2D). Using data from the UCLEB consortium we investigated the relationship between rs10911021 and CHD in T2D, whether rs10911021 was associated with levels of amino acids involved in the γ-glutamyl cycle or any conventional risk factors (CRFs) for CHD in the T2D participants. Methods Four UCLEB studies (n = 6531) had rs10911021 imputation, CHD in T2D, CRF and metabolomics data determined using a nuclear magnetic resonance based platform. Results The expected direction of effect between rs10911021 and CHD in T2D was observed (1377 no CHD/160 CHD; minor allele OR 0.80, 95 % CI 0.60–1.06) although this was not statistically significant (p = 0.13). No association between rs10911021 and CHD was seen in non-T2D participants (11218 no CHD/1274 CHD; minor allele OR 1.00 95 % CIs 0.92–1.10). In T2D participants, while no associations were observed between rs10911021 and the nine amino acids measured, rs10911021 was associated with HDL-cholesterol (p = 0.0005) but the minor "protective" allele was associated with lower levels (−0.034 mmol/l per allele). Focusing more closely on the HDL-cholesterol subclasses measured, we observed that rs10911021 was associated with six large HDL particle measures in T2D (all p < 0.001). No significant associations were seen in non-T2D subjects. Conclusions Our findings are consistent with a true association between rs10911021 and CHD in T2D. The protective minor allele was associated with lower HDL-cholesterol and reductions in HDL particle traits. Our results indicate a complex relationship between rs10911021 and CHD in T2D.