Tumor necrosis factor alpha and lymphotoxin alpha haplotypes in idiopathic recurrent pregnancy loss.
OBJECTIVE
To investigate the contribution of the -238G/A and -308G/A tumor necrosis factor (TNF) alpha, and +252A/G lymphotoxin (LT) alpha gene polymorphisms to idiopathic recurrent miscarriage (RM).


METHODS
A retrospective case-control study.


METHODS
Outpatient maternity center.


METHODS
Study subjects comprised 372 RM women and 274 age-matched parous control women.


METHODS
None.


METHODS
The TNFalpha and LTalpha gene variants and idiopathic RM.


RESULTS
Higher prevalence of TNFalpha -238A and LTalpha +252G alleles and LTalpha +252G/G genotype and lower frequencies of TNFalpha -308G/A were seen in RM cases. Three-loci haplotype analysis (TNFalpha -308GA/TNFalpha -238GA/LTalpha +252AG) demonstrated significant association between TNFalpha-LTalpha gene variants and RM. Both protective [-308A/-238G/+252A], and susceptible [-308G/-238A/+252G] haplotypes were identified. Mutlivariate regression analysis confirmed the association of -308G/-238A/+252G haplotype with exclusively early RM, after controlling for a number of covariates; no specific TNFalpha and LTalpha genotypes or haplotypes were linked with either late or combined early and late RM.


CONCLUSIONS
The TNFalpha -238G/A and LTalpha +252A/G, but not TNFalpha -308G/A, polymorphic variants are associated with exclusively early idiopathic RM.
Zammiti
Walid
W
Faculty of Pharmacy, Research Unit of Hematologic and Autoimmune Diseases, University of Monastir, Monastir, Tunisia.
Mtiraoui
Nabil
N
Finan
Ramzi R
RR
Almawi
Wassim Y
WY
Mahjoub
Touhami
T
D000026:Abortion, Habitual / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008233:Lymphotoxin-alpha / Q000235:genetics*; D011247:Pregnancy; D012189:Retrospective Studies; D012307:Risk Factors; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha