Variants of ADRA2A are associated with fasting glucose, blood pressure, body mass index and type 2 diabetes risk: meta-analysis of four prospective studies
Year: 2011
Type: review
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.
Source: Diabetologia
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,490
Funders: John D. and Catherine T. MacArthur Foundation, Government of the United Kingdom, National Institute for Health and Care Research, British Heart Foundation, Health and Safety Executive, University of Bristol, National Institutes of Health, U.S. Public Health Service, Medical Research Council, National Institute on Aging, National Heart, Lung, and Blood Institute
Awards: G1008933337, G1170877802, G1278592377, G1742338229, G232751712, G2359252135, G2524631004, G2587446714, G2611761805, G269567959, G2747526898, G2751663742, G2881217387, G3030466631, G3383031331, Utilising genetic tools to dissect causal pathways in cardiovascular disease: deployment of a 50K high density SNP array in the Whitehall II prospective study, RENEWAL: Dissecting the molecular genetic architecture of plasma lipid traits: identifying functional changes and their use in determining coronary heart disease causality, The integration of the knowledge of genes involved in heart development and cardiovascular processes from biomedical research, using standardised gene ontology, G4574633762, G4722625316, G4892861650, G5208912463, G5412976545, G6060264546, G6354209809, G6617088278, CHANGES IN HEALTH: SOCIO-ECONOMIC STATUS AND PATHWAYS, G7227442497, G7359874357, G7724270072, Genetic risk factors for cardiovascular disease in the British Women’s Heart and Health Study, G8115415269, RENEWAL: Psychosocial and biological factors in the occurrence of cardiovascular disease: the Whitehall II study, G8259616008, Socio-economic status and heterogeneity in aging, Socioeconomic gradient in CHD in early old age, G8898901431, G9000199375, English Longitudinal Study of Ageing - Renewal 2024
OpenAlex ID: W2000228358