title: Methylenetetrahydrofolate reductase C677T and A1298C polymorphism and changes in homocysteine concentrations in women with idiopathic recurrent pregnancy losses.
abstract: 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.
authors.affiliation: Research Unit of Hematological and Autoimmune diseases, Faculty of Pharmacy, Monastir, Center University, Tunisia.
authors.forename: N
authors.initials: N
authors.lastname: Mtiraoui
authors.forename: W
authors.initials: W
authors.lastname: Zammiti
authors.forename: L
authors.initials: L
authors.lastname: Ghazouani
authors.forename: N Jmili
authors.initials: NJ
authors.lastname: Braham
authors.forename: S
authors.initials: S
authors.lastname: Saidi
authors.forename: R R
authors.initials: RR
authors.lastname: Finan
authors.forename: W Y
authors.initials: WY
authors.lastname: Almawi
authors.forename: T
authors.initials: T
authors.lastname: Mahjoub
mesh_terms: D000026:Abortion, Habitual / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D004522:Educational Status; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications* / Q000235:genetics; D016015:Logistic Models; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D012189:Retrospective Studies; D012307:Risk Factors; D014416:Tunisia
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2)