Association of CTLA-4 and TNF-α polymorphism with recurrent miscarriage among North Indian women.
BACKGROUND
CTLA-4 is engaged on effector cells that may alter signal transduction and subsequently cytokine production. The transmission of longer repeats of (AT)(n) alleles of CTLA-4 is also associated with women undergoing recurrent miscarriage. The TNF-α known as an embryo-toxic cytokine is reported to be greater in placentas of abortion prone pregnancies.


OBJECTIVE
The present study investigated the role of CTLA-4+49 A/G, CTLA-4 (AT)(n) 3'UTR, TNF-α-308G/A and TNF-α-238G/A polymorphisms as a susceptibility marker for recurrent miscarriage (RM).


METHODS
We genotyped CTLA4+49 A/G, TNF-α-308 and TNF-α-238 gene polymorphisms in 300 patients with RM and 500 age and ethnically matched negative controls using PCR-RFLP method. While gene sequencing method was adopted for studying the CTLA-4 (AT)(n) 3'UTR polymorphism.


RESULTS
The mutant homozygous genotype GG of CTLA4+49A/G, AA genotype and A allele of TNF-α-308, G allele of TNF-α-238 were observed to be predisposing among RM cases along with the 104 bp, 106 bp, 110 bp and 116 bp alleles of CTLA-4 (AT)(n) microsatellite repeat. GA and AG haplotypes of TNF-α were low risk associated haplotypes among recurrent miscarriage women.


CONCLUSIONS
Roles of CTLA-4 A49G, CTLA-4 (AT)(n) 3'UTR, TNF-α-308 and TNF-α-238 polymorphisms in RM cases from North India is reflected through this study.
Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow 226 014, UP, India.
Rekha
R
Gupta
Swayam
S
Prakash
Farah
F
Parveen
Suraksha
S
Agrawal
D000026:Abortion, Habitual / Q000235:genetics*; D060908:CTLA-4 Antigen / Q000235:genetics*; D016022:Case-Control Studies; D016001:Confidence Intervals; D003710:Demography; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007194:India; D015201:Meta-Analysis as Topic; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha