Non‐Latin European descent could be a requirement for association of NTDs andMTHFRvariant 677C > T: A meta‐analysis

Abstract

There are several studies that have found a positive association between neural tube defects (NTDs) and the common mutation 677C > T of 5,10-methylenetetrahydrofolate reductase (MTHFR), and others that have not found such an association. We updated the meta-analyses of the published data about NTDs and MTHFR 677C > T variant from January 1994 to October 2005 identifying 170 potentially relevant studies. After applying pertinent exclusion criteria, 37 different populations from 32 studies were included in the meta-analysis, with a total of 3,530 cases and 6,296 controls. Further we stratified the data according to geographical region and ethnicity, and produced two separated meta-analyses for non-Latin European and Latin European descent populations. The general (odds ratio 1.41; 95% confidence interval 1.24-1.59), and the non-Latin European meta-analyses (1.62; 1.38-1.90) indicate an association of TT genotype and NTDs; no association was demonstrated for Latin European populations (1.16; 0.95-1.43). The examination of non-Latin European studies revealed that the association of TT genotype with NTD has only been proven for Irish populations, both by case-control studies, and by family-based tests, such as the allele transmission disequilibrium test (TDT).

Polymorphisms of methylenetetrahydrofolate reductase and methionine synthase genes and bladder cancer risk: a case–control study with meta-analysis

“…Therefore, we performed a meta-analysis to assess the association between the C677T polymorphism and risk of bladder cancer. Our meta-analysis results indicated that the MTHFR C677T polymorphism was not associated with bladder cancer risk, which was consistent with the published meta-analysis data on other cancers in Caucasians [40,41]. However, we found an increased risk effect for 677T allele on risk of bladder cancer in Asians (our present study).…”

Association between MTHFD1 G1958A Polymorphism and Neural Tube Defects Susceptibility: A Meta-Analysis

“…Therefore, folate-related genes widely investigated for their potential involvement in pathogenesis of NTDs. To date, several meta-analyses have been conducted to investigate the association between NTDs and SNPs for candidate genes involved in the folate pathway, including C677T and A1298C in the MTHFR (methylenetetrahydrofolate reductase) gene [37]–[39], A66G in the MTRR (methionine synthase reductase) gene [1], [39], A2756G in the MTR (methionine synthase) gene [39]–[41], and A80G in the RFC-1 (reduced folate carrier) gene [39], [42]. However, no meta-analysis has been conducted on the effect of the MTHFD1 genetic polymorphism on susceptibility to NTDs.…”

Estudio de asociación de base familiar entre polimorfismos de MTHFR y mielomeningocele en Chile

“…Dentro de estos estudios para la variante c.C677T, considerando trabajos que incluyeron principalmente poblaciones de origen caucásica, Van der Put et al 8 demostraron que dicho polimorfismo constituía un marcador de aumento de riesgo de manifestar DTN en todas las poblaciones analizadas, excepto para la italiana. Diez años después, Amorim et al 9 publicaron un meta-análisis considerando poblaciones de todos los orígenes étnicos. Estos autores, al igual que Van der Put el al 8 , confirmaron que la variante c.C677T era un factor de riesgo.…”

“…8 sociedad Pro ayuda del niño lisiado (teleton-chile). 9 En Chile, su prevalencia es de 0,5-0,8/1.000 nacimientos, de los cuales cerca del 50% corresponden a espina bífida (EB). Dentro de los pacientes con EB, la mayoría de ellos corresponden a mielomeningocele (MM) 2,3 .…”

“…Las variantes no sinónimas del gen MTHFR: p.Ala222Val (c.C677T) y p.Glu429Ala (c.A1298C), que se asocian a disminución de la actividad de la enzima, han sido las más estudiadas como posibles factores etiológicos de DTN 7 . No obstante, se han descrito resultados controversiales respecto a la asociación de estas variantes con el riesgo de presentar DTN en varias poblaciones, inconsistencias que podrían ser explicadas por el diferente origen étnico de dichas muestras [8][9][10] . Se ha descrito además que el uso de acido fólico induciría una selección genética en favor de los alelos asociados a una menor actividad de MTHFR (677T y 1298C) 11,12 .…”