NDLI: 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

Content Provider	Springer Nature : BioMed Central
Author	Beaney, Katherine E. Cooper, Jackie A. McLachlan, Stela Wannamethee, S. Goya Jefferis, Barbara J. Whincup, Peter Ben-Shlomo, Yoav Price, Jacqueline F. Kumari, Meena Wong, Andrew Ong, Ken Hardy, Rebecca Kuh, Diana Kivimaki, Mika Kangas, Antti J. Soininen, Pasi Ala-Korpela, Mika Drenos, Fotios Humphries, Steve E.
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.
Related Links	https://cardiab.biomedcentral.com/counter/pdf/10.1186/s12933-016-0435-0.pdf
Ending Page	11
Page Count	11
Starting Page	1
File Format	HTM / HTML
ISSN	14752840
DOI	10.1186/s12933-016-0435-0
Journal	Cardiovascular Diabetology
Issue Number	1
Volume Number	15
Language	English
Publisher	BioMed Central
Publisher Date	2016-08-22
Access Restriction	Open
Subject Keyword	Diabetes Angiology Cardiology Coronary heart disease Metabolomics HDL-cholesterol Genetic risk
Content Type	Text
Resource Type	Article
Subject	Cardiology and Cardiovascular Medicine Internal Medicine Endocrinology, Diabetes and Metabolism
Journal Impact Factor	8.5/2023
5-Year Journal Impact Factor	8.9/2023

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