Heterozygote advantage of the MTHFR gene in patients with neural-tube defect and their relatives

Reply to comment on: Biason-Lauber A, Boehm B, Lang-Muritano M et al. (2005) Association of childhood type 1 diabetes mellitus with a variant of PAX4: possible link to beta cell regenerative capacity. Diabetologia 48:900–905

“…The most probable explanation for this phenomenon is that the polymorphism represents a heterozygote advantage, one of the known causes of deviation from HWE (together with outbreeding, mutations, gene migration, genetic drift and non-random mating). This is not an isolated phenomenon as it has been previously described and discussed [2][3][4][5][6]. That the A/C genotype might confer a functional advantage is also confirmed by our expression studies.…”

Study of MTHFR and MS polymorphisms as risk factors for NTD in the Italian population

“…confirm this mutation as a major determinant for NTD (Papapetrou et al 1996;Mornet et al 1997;Speer et al 1997;Boduroglu et al 1998;Koch et al 1998;Weitkamp et al 1998;Shaw et al 1999). The C677T mutation was studied in the Italian population, which has a relatively low prevalence of NTDs.…”

No evidence for heterozygote advantage at MTHFR in patients with lumbosacral myelomeningocele or their relatives

“…Weitkamp et al 1 reported a heterozygote advantage of the MTHFR gene in patients with neural tube defects (NTD) and their relatives. A C-to-T substitution at nucleotide 677 that converts an alanine to a valine residue in the 5,10-methylenetetrahydofolate-reductase gene (MTHFR) yields a common thermolabile variant (T) with 30% to 50% activity of the allelic form (C).…”

“…Homozygosity for the C677T allele has been shown to be more prevalent in individuals with NTD and their parents, as compared to controls in several studies. [2][3][4][5] Weitkamp et al 1 used a data sample of 168 families with NTD pregnancy (81 anencephaly, 1 encephalocele, and 86 spina bifida). The families were from a variety of ethnic origins consisting of 92.3% Western European, 7.0% Native American, 0.4% African American, and 0.3% Asian.…”