Association between ADRA1A gene and the metabolic syndrome: candidate genes and functional counterpart in the PAMELA population

Grassi, G. et al. (2011) Association between ADRA1A gene and the metabolic syndrome: candidate genes and functional counterpart in the PAMELA population. Journal of Hypertension, 29(6), pp. 1121-1127777777777. (doi: 10.1097/HJH.0b013e328346d72c)

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Objectives There is currently uncertainty about whether metabolic syndrome has a common underlying process. We performed a gene-centric association study of metabolic syndrome in 98 major cardiometabolic genes in the large, well phenotyped Pressioni Arteriose Monitorate e Loro Associazioni (PAMELA) study. We followed this with functional studies to elucidate a possible mechanism for the top association signal. Methods From the PAMELA cohort, we sampled 1407 individuals with information on the metabolic syndrome (ATPIII criteria). We analyzed 1324 tagging single-nucleotide polymorphisms (SNPs) in 98 candidate genes selected, based on known pathways involved in sympathetic nervous system, oxidative stress, renin-angiotensin system and sodium balance. Results The SNP rs17055869 near the alpha-1A-adrenoreceptor gene (ADRA1A) showed the strongest association with metabolic syndrome (odds ratio 1.7, CI 1.3-2.2; P=0.00007, P=0.000098 after permutation). In order to determine a functional basis for this association, we examined in a subgroup of metabolic syndrome patients whether the allelic distribution of the above mentioned gene is different according to the different degree of the metabolic syndrome-related sympathetic activation, directly assessed by the gold standard method to assess neuroadrenergic drive, that is microneurographic recording of efferent postganglionic muscle sympathetic nerve traffic. All metabolic syndrome patients with a lesser degree of sympathetic activation were homozygous for the major allele (C), whereas those with a very pronounced sympathetic overdrive had an over-representation of the minor T allele (P<0.0001). Conclusion Thus, the rs17055869 SNP near the 3' end of ADRA1A is significantly associated with metabolic syndrome and it may be involved in determining a greater level of sympathetic activation in metabolic syndrome patients.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Lee, Dr Wai Kwong and Menni, Ms Cristina and Padmanabhan, Professor Sandosh
Authors: Grassi, G., Padmanabhan, S., Menni, C., Seravalle, G., Lee, W.K., Bombelli, M., Brambilla, G., Quarti-Trevano, F., Giannattasio, C., Cesana, G., Dominiczak, A., and Mancia, G.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Journal of Hypertension

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