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Mol. Hum. Reprod. Advance Access published online on November 5, 2009
Molecular Human Reproduction, doi:10.1093/molehr/gap096
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© The Author 2009. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Genetic Association of Phase I and Phase II Detoxification Genes with Recurrent Miscarriages among North Indian Women

F. Parveen1, R.M. Faridi1, V. Das2, G. Tripathi1 and S. Agrawal1,*

1Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow (UP) India 2Department of Obstetrics and Gynecology, Queen Mary Hospital, CSMMU, Lucknow (U.P), India

* Name and address of the corresponding author: Dr. Suraksha Agrawal, Prof. and HOD, Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow (UP) 226014 India, Phone: 091-522 -2668004-8 Ext 2338 (O), 2346, 2347, 2339(R), Fax No. 091-522 -26680973/6680017, Email: suraksha{at}sgpgi.ac.in

Allelic variants of the detoxification genes that have impaired biotransformation functions may increase susceptibility to reproductive toxicity leading to endometriosis, recurrent miscarriage (RM) or poor pregnancy outcome. In the present study, we have investigated CYP1A1, CYP2D6, GSTT1, GSTP1 and GSTM1, which are involved in the phase I and phase II detoxification systems, in relation to their role in the etiology of unexplained recurrent miscarriages (RM). In a case control study, we have investigated 200 females with RM and 300 age and ethnically matched healthy controls with successful reproductive history from North India. The frequencies of phase I wild-type genotypes of CYP1A1 and CYP2D6 in RM cases were 0.56 and 0.60, whereas in controls these were 0.68 and 0.65 respectively (both p<0.05). The GSTM1 null-genotype frequencies were 0.66 and 0.84 among RM cases and controls respectively, the GSTT1 null- genotype frequencies were 0.52 and 0.45 (p<0.005) and the GSTP1 variant allele frequencies were 0.23 and 0.20 respectively. In conclusion, we observed significant protective effects of phase I wild-type genotypes and association of the GSTT1 null genotype with RM. Through combined analyses we have highlighted the importance of the balance of phase I/phase II detoxification systems, in the etiology of recurrent miscarriage.

Key Words: Recurrent Miscarriages (RM)/Phase I and Phase II detoxification systems/Null Genotype/SNPs

Submitted on June 17, 2009; resubmitted on September 29, 2009; accepted on October 28, 2009.


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