Elucidating the genetic susceptibility of hypertension associated microalbuminuriagenome wide scan

Résumé

Objective: To identify genetic susceptibility variants for hypertension associated microalbuminuria. Methods: The study design was a nested case-control genetic association study. Three hundred and three patients were selected from one prospective cohort recruited in the hypertension clinic of two different hospitals with the objective of identify clinical factors associated with microalbuminuria. All the patients were less than 50y, hypertensive grade I and naïve regarding to the treatment at the time of the recruitment. Cases were those who developed microalbuminuria (UAE>=30 mg/day) during the follow up and controls were those who remained with an UAE less than 30 mg/day. UAE was assessed in 24 hour urinary and in two or three samples. The Nsp array of the Affymetrix Gene-Chip Human Mapping 500K was used for genotyping, BRLMM algorithm for inferring the genotypes and PLINK software for performing the association analysis after quality control procedures. Results: The final sample size compromised of 201 controls and 102 cases with genotypes for 250000 SNPs. A few polymorphisms and haplotypes resulted in an association with the presence of an increment in UAE expressed as a qualitative or as a quantitative trait. The significantly associated loci were 8p22 for UAE as a qualitative trait and 8q12.1, 2p11.2, 9p22.2 and 18q23 for the quantitative trait. Some possible candidate genes within the significantly associated loci are: MSR1 for the qualitative trait and IMPAD1, REEP1, BNC2, and CNDP1 for the quantitative trait. There was another group of SNPs which did not reach the statistical significance but they seemed to stand out from the rest of SNPs. Within those regions there were also some possible candidate genes such as ELMO, LOX1, NRP1 or PEBP1 among others. Conclusions: GWAS strategy has enabled the identification of some genomic areas with potential influence on UAE in hypertensive patients. We were able to replicate some of the previously reported linked or associated loci with renal damage.