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

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.

journal_name

Diabetologia

journal_title

Diabetologia

authors

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

doi

10.1007/s00125-011-2108-6

subject

Has Abstract

pub_date

2011-07-01 00:00:00

pages

1710-9

issue

eissn

0012-186X

issn

1432-0428

journal_volume

pub_type

杂志文章,meta分析

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