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Reproduction (2006) 131 395-401
DOI: 10.1530/rep.1.00815
Copyright © 2006 Society for Reproduction and Fertility
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RESEARCH

Methylenetetrahydrofolate reductase C677T and A1298C polymorphism and changes in homocysteine concentrations in women with idiopathic recurrent pregnancy losses

N Mtiraoui, W Zammiti, L Ghazouani, N Jmili Braham, S Saidi, R R Finan1, W Y Almawi2 and T Mahjoub

Research Unit of Hematological and Autoimmune diseases, Faculty of Pharmacy, Monastir, Center University, Tunisia, 1 Faculté de Médecine, Université St Joseph, Beirut, Lebanon, and 2 Al-Jawhara Center for Molecular Medicine, Genetics and Inherited Diseases, College of Medicine & Medical Sciences, Arabian Gulf University, Manama, Bahrain

Correspondence should be addressed to W Y Almawi; Email: wyalmawi{at}yahoo.co.uk

Because they have been described as strong risk factors for idiopathic recurrent pregnancy losses (RPLs), we assessed the association between the methylenetetrahydrofolate reductase (MTHFR) single-nucleotide polymorphisms (SNPs) C677T and A1298C and hyperhomocysteinemia in Tunisian women with idiopathic RPL. Study subjects comprised 200 patients with more than three consecutive RPLs, and 200 age-matched parous control women. C677T and A1298C SNPs were analyzed by PCR-RFLP analysis, and fasting serum homocysteine was measured with ELISA. The frequency of MTHFR 677T/T (30.0 vs 7.0%) and 1298C/C (13.5 vs 4.0%) genotypes was significantly higher in patients. While it was similar among patients and controls (P = 0.095), higher homocysteine was seen with the T/T (but not 1298A/C and 1298C/C) genotype among patients and controls compared with non-T/T carriers (P < 0.05), and in patients vs controls. Higher prevalence of MTHFR 677T/T was seen in late (P < 0.05) and early-late (P < 0.001) RPL, while higher prevalence of 1298C/C genotype was seen only in early-late RPL (P < 0.001), and the prevalence of double heterozygotes was statistically not significant between patients and controls (P = 0.10; odds ratio = 2.73). Logistic regression analysis showed that, after adjusting for all variables, homozygosity for MTHFR C677T was associated with late (P < 0.001), and combined early-late (P < 0.001), while homozygosity for A1298C was associated only with combined early-late (P = 0.026), as was secondary-level education, which was associated with early (P = 0.005), late (P = 0.026) and combined early-late (P = 0.004) abortions. Homozygosity for MTHFR C677T (late and early-late) and A1298C (early-late) are risk factor for RPLs, irrespectively of total homocysteine levels.




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