Homozygous deletion of glutathione S-transferase theta 1 and mu 1 increase the risk of non-syndromic oral clefts in a Mexican population.

OBJECTIVE: To investigate whether null variants of Glutathione S-transferase Mu 1 (GSTM1) and GST Theta 1 (GSTT1) in infants and mothers, as well as maternal exposures to environmental factors, contribute to the risk of non-syndromic cleft lip with or without palate (NSCL/P) in a Mexican population. DESIGN: We performed a matched pair case-control study, including 98 cases and 98 controls and their mothers. Sociodemographic information and environmental exposures were collected by a questionnaire. Null variants of GSTM1 and GSTT1 were assessed by multiplex Polymerase Chain Reaction (PCR). Odds ratios (OR) and their 95 % confidence intervals (CI) were calculated to estimate risks. The interaction of genetic variables with smoking and adjusted ORs were evaluated by binary logistic regression. RESULTS: Homozygous null GSTM1 was associated with the risk of NSCL/P when present in mothers (OR = 2.45, 95 % CI 1.23-4.86) or infants (OR = 2.98, 95 % CI 1.45-6.14). A higher risk was also found when children carried the homozygous null GSTT1 (OR = 4.89, 95 % CI 2.42-9.87). In mothers, this variant showed a crude risk of 9.17 (95 % CI 3.95-21.29), which increased to OR = 13.81 (95 % CI 1.63-117.09) upon interaction with frequent passive smoking (5-7 days/week). Sociodemographic and other environmental exposures were not significantly associated with the risk of NSCL/P. CONCLUSIONS: Maternal and infant GSTT1 and GSTM1 homozygous null genotypes were associated with a higher risk of NSCL/P, and the results suggest an interaction of the maternal GSTT1-null/null genotype with frequent passive smoking.