Diacylglycerol Kinase K Variants Impact Hypospadias in a California Study Population

Details

• Alternative Title:
  J Urol
• Personal Author:
  Carmichael, Suzan L. ; Mohammed, Nebil ; Ma, Chen ; Iovannisci, Dave ; Choudhry, Shweta ; Baskin, Larry S. ; Witte, John S. ; Shaw, Gary M. ; Lammer, Edward J.
• Description:
  PURPOSE ; A recent genome-wide association study reported the novel finding that variants in diacylglycerol kinase kappa (DGKK) were associated with hypospadias. Our objectives were to determine whether this finding could be replicated in a more racially-ethnically diverse study population of California births and to provide a more comprehensive investigation of variants. ; METHODS ; We examined the association of 27 DGKK SNPs with hypospadias, relative to population-based non-malformed controls born in selected California counties from 1990-2003. Analyses included a maximum of 928 controls and 665 cases (91 mild, 336 moderate, 221 severe, 17 undetermined). Results for mild and moderate cases were similar so they were grouped together. ; RESULTS ; For mild and moderate cases, odds ratios (OR) for 15 of the 27 SNPs had p-values <0.05; two were <1, and the others ranged from 1.3 to 1.8. Among severe cases, ORs tended to be closer to one and none of the p-values were <0.05. Due to high LD across the SNPs, haplotype analyses were conducted, and two blocks were generated. These analyses identified a set of eight variants that was associated with a three- to four- fold increased risk, relative to the most common haplotype, regardless of severity of the phenotype (the OR was 4.1, p<10-4 for mild to moderate cases and 3.3, p=0.001 for severe cases). ; CONCLUSIONS ; This study confirms that DGKK variants are associated with hypospadias. Further studies are needed to enable a more thorough investigation of DGKK variability and to delineate the mechanism by which DGKK contributes to urethral development.
• Subjects:
  • California
  • Case-Control Studies
  • Diacylglycerol Kinase
  • Genetic Variation
  • Humans
  • Hypospadias
  • Infant, Newborn
  • Male
  • Polymorphism, Single Nucleotide
• Keywords:
  • HYPOSPADIAS
  • GENES
• Source:
  J Urol. 189(1):305-311
• Pubmed ID:
  23177175
• Pubmed Central ID:
  PMC3973486
• Document Type:
  Journal Article
• Funding:
  6U01DD000489/DD/NCBDD CDC HHSUnited States/ ; R01 ES017060/ES/NIEHS NIH HHSUnited States/ ; R01ES017060/ES/NIEHS NIH HHSUnited States/ ; R01 DK058105/DK/NIDDK NIH HHSUnited States/ ; U01 DD000489/DD/NCBDD CDC HHSUnited States/
• Volume:
  189
• Issue:
  1
• Download URL:
  https://stacks.cdc.gov/view/cdc/33671/cdc_33671_DS1.pdf
• File Type:
  [PDF - 345.39 KB]
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:62e8f23e176d8b8277e0fec55fc379e9c7202a64aded1ee867d6125f880ba06f2e5723ea3f4bdf13bfebce85745eb1b50a029288c5e4aea41577140dfc19afcd