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The alpha_2A-adrenoceptor, which is encoded by the ADRA2A gene, plays a key role in the pathogenesis of diabetes. The different ADRA2A variants and their associations with type 2 diabetes were investigated in a meta-analysis of four prospective studies. Genotyping for ADRA2A single nucleotide polymorphisms was performed and 12 SNPS were identified. Data for the SNPs rs553668 and rs10885122 were available for > 17,000 subjects, of whom 1,307 were diagnosed with T2DM. Other evaluations included insulin resistance using homeostasis model assessment and fasting glucose levels. Several SNPs were associated with metabolic traits and rs553668 was significantly associated with T2DM risk and fasting glucose. Other important SNPs identified were rs553668 and rs17186196 which were both independently linked to fasting glucose. Additionally, rs17186196 was also associated with fasting insulin and insulin resistance. Rs491589 was associated with blood pressure and rs36022820 with body mass index. The genotyping study showed significant associations of different ADRA2A SNPs with T2DM risk, metabolic status and hypertension. This suggests that the alpha_2A-adrenoceptor and its encoding gene are potential targets in diabetes and metabolic disorders therapy : 1710).

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