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J Urol. 2012 Aug;188(2):514-20. doi: 10.1016/j.juro.2012.04.001. Epub 2012 Jun 15.

Pilot genome-wide association search identifies potential loci for risk of erectile dysfunction in type 1 diabetes using the DCCT/EDIC study cohort.

Author information

1
Department of Urology, University of Washington School of Medicine, Seattle, Washington 98195, USA.

Abstract

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 (Illumina®) 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 × 10(-6), including rs9810233 with p = 7 × 10(-7) and rs1920201 with p = 9 ×10(-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 × 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
PMCID:
PMC3764461
DOI:
10.1016/j.juro.2012.04.001
[Indexed for MEDLINE]
Free PMC Article

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