Pilot Genome-Wide Association Search Identifies Potential Loci for Risk of Erectile Dysfunction in Type 1 Diabetes Using the DCCT/EDIC Study Cohort.
J Urol. 2012 Jun 13;
Authors: Hotaling JM, Waggott DR, Goldberg J, Jarvik G, Paterson AD, Cleary PA, Lachin J, Sarma A, Wessells H, Group
PURPOSE: We identified genetic predictors of diabetes associated erectile dysfunction using genome-wide and candidate gene approaches in a cohort of men with type 1 diabetes. MATERIALS AND METHODS: We examined 528 white men with type 1 diabetes, including 125 with erectile dysfunction, from DCCT (Diabetes Control and Complications Trial) and its observational followup, the EDIC (Epidemiology of Diabetes Interventions and Complications) study. Erectile dysfunction was identified from a single International Index of Erectile Function item. A Human1M BeadChip (IlluminaÃÂ®) was used for genotyping. A total of 867,125 single nucleotide polymorphisms were subjected to analysis. Whole genome and candidate gene approaches were used to test the hypothesis that genetic polymorphisms may predispose men with type 1 diabetes to erectile dysfunction. Univariate and multivariate models were used, controlling for age, HbA1c, diabetes duration and prior randomization to intensive or conventional insulin therapy during DCCT. A stratified false discovery rate was used to perform the candidate gene approach. RESULTS: Two single nucleotide polymorphisms located on chromosome 3 in 1 genomic loci were associated with erectile dysfunction with p <1 ÃÂ 10(-6), including rs9810233 with p = 7 ÃÂ 10(-7) and rs1920201 with p = 9 ÃÂ10(-7). The nearest gene to these 2 single nucleotide polymorphisms is ALCAM. Genetic association results at these loci were similar on univariate and multivariate analysis. No candidate genes met the criteria for statistical significance. CONCLUSIONS: Two single nucleotide polymorphisms, rs9810233 and rs1920101, which are 25 kb apart, are associated with erectile dysfunction, although they do not meet the standard genome-wide association study significance criterion of p <5 ÃÂ 10(-8). Other studies with larger sample sizes are required to determine whether ALCAM represents a novel gene in the pathogenesis of diabetes associated erectile dysfunction.
PMID: 22704111 [PubMed - as supplied by publisher]