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

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 indi...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer-Verlag 2011
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3110279/
https://www.ncbi.nlm.nih.gov/pubmed/21455730
http://dx.doi.org/10.1007/s00125-011-2108-6
Descripción
Sumario: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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00125-011-2108-6) contains supplementary material, which is available to authorised users.

Ejemplares similares