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


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.
Department of Urology, University of Washington School of Medicine, Seattle, Washington 98195, USA.
James M
JM
Hotaling
Daryl R
DR
Waggott
Jack
J
Goldberg
Gail
G
Jarvik
Andrew D
AD
Paterson
Patricia A
PA
Cleary
John
J
Lachin
Aruna
A
Sarma
Hunter
H
Wessells
D000483:Alleles; D015703:Antigens, CD / Q000235:genetics*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000188:drug therapy / Q000235:genetics*; D007172:Erectile Dysfunction / Q000235:genetics*; D005326:Fetal Proteins / Q000235:genetics*; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007328:Insulin / Q000008:administration & dosage; D008297:Male; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018570:Risk Assessment; D020410:Activated-Leukocyte Cell Adhesion Molecule
D015703:Antigens, CD; D015816:Cell Adhesion Molecules, Neuronal; D005326:Fetal Proteins; D007004:Hypoglycemic Agents; D007328:Insulin; C105613:ALCAM protein, human; D020410:Activated-Leukocyte Cell Adhesion Molecule