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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.

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Beaney, Katherine E 
Cooper, Jackie A 
McLachlan, Stela 
Wannamethee, S Goya 
Jefferis, Barbara J 


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.



Coronary heart disease, Genetic risk, HDL-cholesterol, Metabolomics, Aged, Amino Acids, Biomarkers, Cholesterol, HDL, Chromosomes, Human, Pair 1, Coronary Disease, DNA, Intergenic, Diabetes Mellitus, Type 2, Down-Regulation, Female, Gene Frequency, Genetic Association Studies, Genetic Predisposition to Disease, High-Throughput Screening Assays, Humans, Magnetic Resonance Spectroscopy, Male, Metabolomics, Middle Aged, Particle Size, Phenotype, Polymorphism, Single Nucleotide, Protective Factors, Risk Assessment, Risk Factors

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Cardiovasc Diabetol

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Springer Science and Business Media LLC