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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

Beaney, Katherine E and Cooper, Jackie A and McLachlan, Stela and Wannamethee, S Goya and Jefferis, Barbara J and Whincup, Peter and Ben-Shlomo, Yoav and Price, Jacqueline F and Kumari, Meena and Wong, Andrew and Ong, Ken and Hardy, Rebecca and Kuh, Diana and Kivimaki, Mika and Kangas, Antti J and Soininen, Pasi and Ala-Korpela, Mika and Drenos, Fotios and Humphries, Steve E (2016) '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.' Cardiovascular Diabetology, 15. ISSN 1475-2840

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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.

Item Type: Article
Uncontrolled Keywords: Coronary heart disease, Metabolomics, HDL-cholesterol, Genetic risk
Subjects: Q Science > QH Natural history > QH426 Genetics
Divisions: Faculty of Social Sciences > Institute for Social and Economic Research
Depositing User: Elements
Date Deposited: 06 Sep 2018 14:59
Last Modified: 06 Sep 2018 14:59
URI: http://repository.essex.ac.uk/id/eprint/22964

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