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Title: 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
Authors: Beaney, KE
Cooper, JA
McLachlan, S
Wannamethee, SG
Jefferis, BJ
Whincup, P
Ben-Shlomo, Y
Price, JF
Kumari, M
Wong, A
Ong, K
Hardy, R
Kuh, D
Kivimaki, M
Kangas, AJ
Soininen, P
Ala-Korpela, M
Drenos, F
Humphries, SE
Keywords: Coronary heart disease;Metabolomics;HDL-cholesterol;Genetic risk
Issue Date: 2016
Publisher: Springer Verlag
Citation: Cardiovascular diabetology, 2016, 15 (1), pp. 115 - 115
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.
ISSN: 1475-2840
Appears in Collections:Dept of Life Sciences Research Papers

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