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.

• Authors: Anna Verkleij-Hagoort, Johannes Bliek, Fakhredin Sayed-Tabatabaei, Nicolette Ursem, Eric Steegers, Régine Steegers-Theunissen
• Journal: American journal of medical genetics. Part A (Am J Med Genet A) Vol. 143A Issue 9 Pg. 952-60 (May 01 2007) ISSN: 1552-4825 [Print] United States
• PMID: 17431894 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't)

Chemical References

• Methylenetetrahydrofolate Reductase (NADPH2)

Topics

• Case-Control Studies
• Child
• Cleft Lip (genetics)
• Cleft Palate (genetics)
• Female
• Heart Defects, Congenital (genetics)
• Humans
• Hyperhomocysteinemia (genetics)
• Methylenetetrahydrofolate Reductase (NADPH2) (genetics)
• Mothers
• Polymorphism, Single Nucleotide