Promotor genotype of the platelet-derived growth factor receptor-alpha gene shows population stratification but not association with spina bifida meningomyelocele.

Neural tube defects (NTDs) constitute a major group of congenital malformations with an overall incidence of approximately 1-2 in 1,000 live births in the United States. Hispanic Americans have a 2.5 times higher risk than the Caucasian population. Spina bifida meningomyelocele (SBMM) is a major clinical presentation of NTDs resulting from lack of closure of the spinal cord caudal to the head. In a previous study of spina bifida (SB) patients of European Caucasian descent, it was suggested that specific haplotypes of the platelet-derived growth factor receptor-alpha (PDGFRA) gene P1 promoter strongly affected the rate of NTD genesis. In our study, we evaluated the association of PDGFRA P1 in a group of 407 parent-child triads (167 Caucasian, 240 Hispanics) and 164 unrelated controls (89 Caucasian, 75 Hispanic). To fully evaluate the association of PDGFRA P1, we performed both transmission-disequilibrium test (TDT) and association analyses to test the hypotheses that PDGFRA P1 was (1) transmitted preferentially in SBMM affected children and (2) associated with the condition of SBMM comparing affected children to unaffected controls. We did find that there was a different allelic and genotypic distribution of PDGFRA P1 when comparing Hispanics and Caucasians. However, neither ethnic group showed strong association between SBMM and the PDGFRA P1 region. These findings suggest that PDGFRA P1 does not have a major role in the development of SBMM.