Urinary tract anomalies associated with MTHFR gene polymorphism C677T in girls.

BACKGROUND/AIMS Periconceptional folate has a preventive effect not only on neural tube defects, but possibly also on other birth defects such as urinary tract anomalies (UTA), orofacial clefts and conotruncal heart defects. Folate metabolism gene variants are therefore being investigated as potential susceptibility factors. METHODS We assessed the methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C genotypes in 132 UTA patients and 290 controls, also with respect to sex. RESULTS We found a significantly higher incidence of the T allele/TT genotype of the C677T polymorphism in UTA patients compared with controls (p = 0.019/p = 0.044). In the individual sexes, the T allele frequency in UTA girls versus control girls was 42.6 versus 21.7%, p < 0.0001 (OR = 2.68; 95% CI: 1.63-4.40), and the frequency of TT genotypes was 19.2 versus 5.6%, p = 0.02 (OR = 4.0; 95% CI: 1.26-12.69); no difference was observed between the boys' groups. CONCLUSION The higher incidence of the C677T MTHFR gene polymorphism in girls with UTA could point to a developmental difference between the sexes that might be related to sexual dimorphism in methylation due to the lower activity of MTHFR in the system with the highest sexual dimorphism: the urogenital system. Naturally, this assumption should be further tested.