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

P. J. Talmud, J. A. Cooper, T. Gaunt, M. V. Holmes, S. Shah, J. Palmen, F. Drenos, T. Shah, M. Kumari, M. Kivimaki, J. Whittaker, D. A. Lawlor, I. N. Day, A. D. Hingorani, J. P. Casas, S. E. Humphries

Research output: Contribution to journalArticle (Academic Journal)

25 Citations (Scopus)

Abstract

Aims/hypothesis: We quantified the effect of ADRA2A (encoding α-2 adrenergic receptor) variants on metabolic traits and type 2 diabetes risk, as reported in four studies. Methods: 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. Results: 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). Conclusions/interpretation: Multiple ADRA2A SNPs are associated with metabolic traits, blood pressure and type 2 diabetes risk. The α-2 adrenergic receptor should be revisited as a therapeutic target for reduction of the adverse consequences of metabolic trait disorders and type 2 diabetes.

Original languageEnglish
Pages (from-to)1710-1719
Number of pages10
JournalDiabetologia
Volume54
Issue number7
DOIs
Publication statusPublished - 1 Jul 2011

Keywords

  • α-2 Adrenergic receptor
  • ADRA2A
  • Fasting glucose
  • Human CVD BeadChip
  • Meta-analysis
  • Prospective studies
  • rs10885122
  • rs553668
  • TCF7L2
  • Type 2 diabetes mellitus

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    Talmud, P. J., Cooper, J. A., Gaunt, T., Holmes, M. V., Shah, S., Palmen, J., Drenos, F., Shah, T., Kumari, M., Kivimaki, M., Whittaker, J., Lawlor, D. A., Day, I. N., Hingorani, A. D., Casas, J. P., & Humphries, S. E. (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), 1710-1719. https://doi.org/10.1007/s00125-011-2108-6