title: Polymorphism in CYP1A1, GSTMI,        GSTT1 genes and organochlorine pesticides in the etiology of hypospadias.
abstract: Exposure to endocrine-disrupting chemicals (EDCs) and maternal endogenous estrogen may cause hypospadias, common congenital anomaly. Several organochlorine pesticides (OCPs) have been reported to possess an endocrine-disrupting potential. Cytochrome P4501A1 (CYP1A1) and glutathione S-transferases (GSTM1 and GSTT1) of xenobiotic metabolizing enzyme family are involved in the metabolism of various environmental toxicants and steroidal hormones. Hence, the present study was designed to evaluate the role of CYP1A1, GSTM1, GSTT1 genes polymorphism, OCPs levels and risk of hypospadias. A total of 80 hypospadiac and 120 age-matched control boys were included. OCP levels in blood were determined using Gas Chromatograph equipped with electron capture detector (GC-ECD)  and polymorphism in CYP1A1, GSTM1 and GSTT1 genes was evaluated by RFLP and multiplex PCR method. We observed significant high levels of β-hexachlorohexane (HCH), γ-HCH, and p,p'-dichlorodiphenyl-dichloroethylene (p,p'-DDE) in the cases. CYP1A1 polymorphisms were not significantly different among cases and controls, whereas concomitant deletion of GSTM1 and GSTT1 genotypes was significantly higher in cases as compared to controls. However, after adjusting for low birth weight and maternal occupational exposure, the results did not remain significant but odds of risk was higher (OR = 1.72, p = 0.14) among cases. In conclusion, our study suggests irrespective of genetic predisposition, higher level of some OCPs may be associated with increased risk of hypospadias.
authors.affiliation: Environmental Biochemistry & Molecular Biology Laboratory, Department of Biochemistry, University College of Medical Sciences & GTB Hospital, University of Delhi, Dilshad Garden, Delhi, India.
authors.forename: Chandra
authors.initials: C
authors.lastname: Shekharyadav
authors.forename: Minu
authors.initials: M
authors.lastname: Bajpai
authors.forename: Vivek
authors.initials: V
authors.lastname: Kumar
authors.forename: Rafat Sultana
authors.initials: RS
authors.lastname: Ahmed
authors.forename: Piyush
authors.initials: P
authors.lastname: Gupta
authors.forename: Basu Dev
authors.initials: BD
authors.lastname: Banerjee
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D052244:Endocrine Disruptors / Q000097:blood / Q000633:toxicity*; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D006843:Hydrocarbons, Chlorinated / Q000097:blood / Q000633:toxicity*; D007021:Hypospadias / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D007194:India / Q000453:epidemiology; D007223:Infant; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D008297:Male; D016273:Occupational Exposure; D016017:Odds Ratio; D010575:Pesticides / Q000097:blood / Q000633:toxicity*; D011110:Polymorphism, Genetic
chemical_list: D019363:Cytochrome P-450 CYP1A1; D052244:Endocrine Disruptors; D005982:Glutathione Transferase; D006843:Hydrocarbons, Chlorinated; D010575:Pesticides; C413545:glutathione S-transferase T1