Variants of ADRA2A are associated with fasting glucose, blood pressure, body mass index and type 2 diabetes risk: meta-analysis of four prospective studies


Talmud, PJ; Cooper, JA; Gaunt, T; Holmes, MV; Shah, S; Palmen, J; Drenos, F; Shah, T; Kumari, M; Kivimaki, M; Whittaker, J; Lawlor, DA; Day, IN; Hingorani, AD; Casas, JP; Humphries, SE; (2011) Variants of ADRA2A are associated with fasting glucose, blood pressure, body mass index and type 2 diabetes risk: meta-analysis of four prospective studies. Diabetologia, 54 (7). pp. 1710-1719. ISSN 0012-186X DOI: https://doi.org/10.1007/s00125-011-2108-6

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Abstract

We quantified the effect of ADRA2A (encoding alpha-2 adrenergic receptor) variants on metabolic traits and type 2 diabetes risk, as reported in four studies. Genotype data for ADRA2A single nucleotide polymorphisms (SNPs) rs553668 and rs10885122 were analysed in > 17,000 individuals (1,307 type 2 diabetes cases) with regard to metabolic traits and type 2 diabetes risk. Two studies (n = 9,437), genotyped using the Human Cardiovascular Disease BeadChip, provided 12 additional ADRA2A SNPs. Rs553668 was associated with per allele effects on fasting glucose (0.03 mmol/l, p = 0.016) and type 2 diabetes risk (OR 1.17, 95% CI 1.04-1.31; p = 0.01). No significant association was observed with rs10885122. Of the 12 SNPs, several showed associations with metabolic traits. Overall, after variable selection, rs553668 was associated with type 2 diabetes risk (OR 1.38, 95% CI 1.09-1.73; p = 0.007). rs553668 (per allele difference 0.036 mmol/l, 95% CI 0.008-0.065) and rs17186196 (per allele difference 0.066 mmol/l, 95% CI 0.017-0.115) were independently associated with fasting glucose, and rs17186196 with fasting insulin and HOMA of insulin resistance (4.3%, 95% CI 0.6-8.1 and 4.9%, 95% CI 1.0-9.0, respectively, per allele). Per-allele effects of rs491589 on systolic and diastolic blood pressure were 1.19 mmHg (95% CI 0.43-1.95) and 0.61 mmHg (95% CI 0.11-1.10), respectively, and those of rs36022820 on BMI 0.58 kg/m(2) (95% CI 0.15-1.02). Multiple ADRA2A SNPs are associated with metabolic traits, blood pressure and type 2 diabetes risk. The alpha-2 adrenergic receptor should be revisited as a therapeutic target for reduction of the adverse consequences of metabolic trait disorders and type 2 diabetes.

Item Type: Article
Keywords: ADRA2A, alpha-2 Adrenergic receptor, Fasting glucose, Human CVD, BeadChip, Meta-analysis, Prospective studies, rs553668, rs10885122, TCF7L2, Type 2 diabetes mellitus, POLYMORPHISMS, HOMEOSTASIS, LOCI, OBESITY, MICE
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Non-Communicable Disease Epidemiology
Research Centre: Centre for Global Non-Communicable Diseases (NCDs)
PubMed ID: 21455730
Web of Science ID: 291392000017
URI: http://researchonline.lshtm.ac.uk/id/eprint/534

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