Paraoxonase 1 polymorphisms and haplotypes and the risk for having offspring affected with spina bifida in Southeast Mexico

BACKGROUND Spina bifida (SB) is a common congenital malformation in Southeast Mexico. Parents of children with SB reside in areas with frequent pesticide spraying or have agriculture activities, suggesting potential exposure to pesticides. Paraoxonase 1 (PON1) is the responsible enzyme for deactivation of organophosphates (OP) in the central nervous system. Polymorphisms of PON1 genes influence the catalytic activity and plasma protein level of the enzyme, therefore, genotypic characterization of PON1 gene represents a potential predictor for susceptibility to OP‐related effects. METHODS The frequency of PON1 haplotypes and polymorphisms (−108CT, L55M, and Q192R) were determined in this study. A case‐control study was performed to evaluate the risk for having offspring affected by SB in 152 cases and 160 control parents. Polymorphisms were determined by PCR amplification and restriction fragment length polymorphism and Real Time‐PCR. Odds ratios and confidence interval 95% were estimated. RESULTS Genotype frequencies for the three PON1 polymorphisms were distributed according to Hardy–Weinberg expectations (p > 0.05) and were significantly different between cases and controls (p < 0.05). The heterozygous CT genotype of −108CT polymorphism, the RR genotype of Q192R polymorphism, both LM and MM genotypes of L55M polymorphism, and the haplotypes 221 and 222 (for −108CT, L55M, and Q192R) were associated with the risk for having a child affected by SB (p < 0.02). The heterozygous −108CT genotype was associated only maternally, whereas the heterozygous L55M genotype was relevant only in the fathers. The RR homozygous genotype was relevant both in mothers and fathers, suggesting the importance of this substrate‐specific polymorphism. CONCLUSION Results suggest that PON1 polymorphisms are relevant risk factors for having offspring affected with SB in this population from Southeast Mexico. Birth Defects Research (Part A), 2010. © 2010 Wiley‐Liss, Inc.