Hyperhomocysteinemia and MTHFR polymorphisms in association with orofacial clefts and congenital heart defects: A meta‐analysis

Abstract

Several studies have reported an association between hyperhomocysteinemia, 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphisms and cleft lip with or without cleft palate (CLP), and congenital heart defects (CHDs). However, findings have been inconsistent. A meta-analysis was performed of published studies until September 2006 investigating these associations in both mothers and children. Homocysteine data were provided in two CLP and three CHD studies, and MTHFR polymorphisms were reported in ten CLP and eight CHD studies. Data were analyzed using the random effects model in the Cochrane Review Manager. The pooled odds ratio (OR) of maternal hyperhomocysteinemia was 2.3 (95% CI 0.4-11.9) for CLP, and 4.4 (2.6-7.3) for CHDs. The MTHFR C677T polymorphism and CLP showed pooled ORs of 1.2 (0.9-1.5) in mothers and 1.0 (0.9-1.2) in children, whereas these estimates for the A1298C polymorphism were 1.0 (0.7-1.2) in mothers and 0.9 (0.6-1.2) in children. The MTHFR C677T polymorphism in CHD studies demonstrated a pooled OR of 1.0 (0.8-1.3) for mothers and 1.1 (0.9-1.5) for children. Two studies investigating the maternal A1298C polymorphism in CHDs demonstrated a pooled OR of 1.2 (0.8-1.8). Only one CHD study reported an OR of 1.3 (0.8-2.1) for this polymorphism in children. In conclusion, this meta-analysis demonstrates that maternal hyperhomocysteinemia is a risk factor for CHDs. The MTHFR polymorphisms C677T and A1298C in both mothers and children are not independently associated with CLP or CHDs. Future studies should be performed to investigate the interactions between maternal hyperhomocysteinemia, B-vitamin intake, related polymorphisms and the risk of CLP and CHDs.

Combined Effects of Cigarette Smoking and Alcohol Consumption on Perinatal Outcome

“…In addition, alcohol intake and low methylenetetrahydrofolate reductase activity has an adverse effect on the total homocysteine concentration [61] . In addition, in a recent meta-analysis, VerkleijHagoort et al [62] confirmed that hyperhomocysteinemia is a risk factor for congenital heart disease. Another known example is the effect of these substances on antioxidants other than folate.…”

Folate and one‐carbon metabolism gene polymorphisms and their associations with oral facial clefts

“…g Beaty et al [2002], Blanton et al [2000], Chevrier et al [2007], Gaspar et al [2004], Grunert et al [2002], Jugessur et al [2003], Martinelli et al [2001], Mills et al [1999], Mostowska et al [2006], Nurk et al [2004], Pezzetti et al [2004], Prescott et al [2002], Shaw et al [1998], Shi et al [2004], Shotelersuk et al [2003], Tolarova et al [1998], van Rooij et al [2003, Vieira et al [2005], Zhu et al [2006]. h Verkleij-Hagoort et al [2007]. i Martinelli et al [2006], Mostowska et al [2006].…”

Meta-analysis of methylenetetrahydrofolate reductase (MTHFR) A1298C polymorphism and risk of orofacial cleft

“…Several meta-analysis studies illustrate the utility of the technique in identifying genes of small effects like MTHFR with phenotypes like-NTD (Zhang et al, 2013); down syndrome (Zintzaras, 2007;; cardiovascular disease (Xuan et al, 2011), stroke (Yadav et al, 2013); migraine (Shurks et al, 2010), Alzheimer's (Zhang et al, 2010), bipolar disorder (Rai, 2011), and depression (Zintzaras, 2006;. Author identified one meta-analysis (Verkleij-Hagoort et al, 2007) published in 2007 concerning similar topic during the literature search. Verkleij-Hagoort performed a metaanalysis based on eight studies and find meager between MTHFR C677T polymorphisms and orofacial cleft (OR=1.01; 95% CI=0.87-1.16; I 2 =0%).…”