Sunday, March 27, 2011

Novel alleles of HLA-DQ and -DR loci show association with recurrent miscarriages among South Indian women

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Meka Aruna1, Theeya Nagaraja1, Sadaranga Andal Bhaskar2, Surapaneni Tarakeswari3, Alla Govardhan Reddy4, Kumarasamy Thangaraj4, Lalji Singh4 and B. Mohan Reddy1,*
1Molecular Anthropology Group, Biological Anthropology Unit, Indian Statistical Institute, Street No. 8, Habsiguda, Hyderabad 500007, India
2Lakshmi Fertility Clinic, Pogathota, Nellore 524001, India
3Fernandez Hospital, Bogulkunta, Hyderabad 500001, India
4Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500007, India *Correspondence address. E-mail: bmr{at}isi.ac.in; bmrisi{at}gmail.comReceived March 24, 2010. Revision received January 9, 2011. Accepted January 17, 2011. BACKGROUND In this study, recurrent miscarriages (RMs) are defined as loss of two or more clinically detectable pregnancies before 20 weeks of gestation. HLA has been thought to play a role in RM. However, the results of earlier studies on the role of different human leucocyte antigen (HLA) genes were conflicting and inconclusive. In the present study, we investigate HLA genes (HLA-DRA, HLA-DRB1, HLA-DQA1 and HLA-DQB1) in RM couples with unknown etiology and normal couples.

METHODS Blood samples from 143 RM couples and 150 control couples were analyzed, firstly to validate previously reported association studies and secondly to explore whether any novel alleles or haplotypes specific to Indian populations can be observed to be associated with RM. HLA typing was carried out by DNA sequencing.

RESULTS Results suggest an association of the DQB1*03:03:02 allele with RM (odd ratio = 2.66; pc = 0.02; confidence interval = 1.47–4.84). Haplotypes of the DQA1 and DQB1 risk alleles also showed a significant association with RM, albeit not after Bonferroni correction for multiple comparisons.

CONCLUSIONS HLA-DQB1 appears to have a strong involvement in the manifestation of RM in this population from South India. The current genetic analysis of RM and control couples not only highlights the genes exhibiting a strong etiological role but also reflects the protective nature of some HLA genes against RM. Nevertheless, most of these alleles/haplotypes were not those that are implicated in RM in other ethnic backgrounds, and hence require further validation in other populations of India, from different ethnic and/or geographic backgrounds.

© The Author 2011. 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@oup.com This ArticleHum. Reprod. (2011) 26 (4): 765-774. doi: 10.1093/humrep/der024 First published online: February 15, 2011

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