Association of neural tube defects in children of mothers with MTHFR 677TT genotype and abnormal carbohydrate metabolism risk: a case-control study

Abstract

ABSTRACT. Abnormalities in maternal folate and carbohydrate 2201©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 13 (1): 2200-2207 (2014) Combination of risk factors in spina bifida metabolism have both been shown to induce neural tube defects (NTD) in humans and animal models. However, the relationship between these two factors in the development of NTDs remains unclear. Data from mothers of children with spina bifida seen at the Unidad de Espina Bífida del Hospital Infantil Virgen del Rocío (case group) were compared to mothers of healthy children with no NTD (control group) who were randomly selected from patients seen at the outpatient ward in the same hospital. There were 25 individuals in the case group and 41 in the control group. Analysis of genotypes for the methylenetetrahydrofolate reductase (MTHFR) 677CT polymorphism in women with or without risk factors for abnormal carbohydrate metabolism revealed that mothers who were homozygous for the MTHFR 677TT polymorphism and at risk of abnormal carbohydrate metabolism were more likely to have offspring with spina bifida and high levels of homocysteine, compared to the control group. The increased incidence of NTDs in mothers homozygous for the MTHFR 677TT polymorphism and at risk of abnormal carbohydrate metabolism stresses the need for careful metabolic screening in pregnant women, and, if necessary, determination of the MTHFR 677CT genotype in those mothers at risk of developing abnormal carbohydrate metabolism.

The interaction of maternal diabetes with mutations that affect folate metabolism and how they affect the development of neural tube defects in mice

“…This phenotype has not been found previously in this mutant mouse line, although it was associated with NTDs in human patients . Interestingly, studies in humans revealed that mothers homozygous for the MTHFR C677T polymorphism (MTHFR6TT, but not MTHFR 677CT) and at risk of abnormal carbohydrate metabolism had a higher risk of bearing offspring with spina bifida . In the knowledge that this polymorphism is associated with decreased enzyme activity and an increase in blood homocysteine levels our data are also consistent with the idea that only a severe impairment in maternal folate metabolism is capable of inducing NTDs along with maternal diabetes.…”

Prävalenz von Gastroschisis, Omphalozele, Spina bifida und orofazialen Spaltbildungen bei Neugeborenen im Zeitraum Januar 2000–Dezember 2010 in Leipzig, Sachsen, Sachsen-Anhalt und Deutschland

“…Spina bifida, eine Verschlussstörung der Wirbelsäule [5], ist die am weitesten verbreitete Fehlbildung des Neuralrohrs [8]. Sie tritt bei durchschnittlich 10/10 000 Geburten auf [9]. Ein Risikofaktor stellt das Alter der Mutter dar.…”

“…Zwischen den 16 Bundesländern zeigen sich keine erheblichen Unterschiede im Auftreten der 4 zusammengefassten Fehlbildungen. Auffallend sind jedoch die vergleichsweise niedrige Prävalenz in Berlin (9,41/10 000 LB, KI 8,4-10,5) und das scheinbar gehäufte Auftreten von angeborenen Fehlbildungen in Mecklenburg-Vorpommern (17,41/10 000 LB, KI 15,[2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]6). Ursache dafür ist wahrscheinlich der Fehler der kleinen Zahlen, also eine Verfälschung des Ergebnisses aufgrund einer geringen Gesamtmenge.…”

“…Das geringste Auftreten von kongenitalen Malformationen wurde in Berlin (9,41/10 000 LB, KI 8,4-10,5) registriert. Das höchste Auftreten (17,41/10 000 LB,KI 15,[2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]6) zeigte sich in Mecklenburg-Vorpommern.DiskussionBei den gemeldeten Fällen von Omphalozele, Gastroschisis und orofazialen Spaltbildungen beobachteten wir in Deutschland einen statistisch signifikanten Anstieg über den betrachteten Zeitraum, dessen Effektgröße jedoch sehr gering ist (z. B. Omphalozele OR 1,04, KI 1,02-1,05, p-korrigiert < 0,05) und vielmehr auf die hohe ▶Abb.…”

Women with Methylenetetrahydrofolate Reductase Gene Polymorphism and the Need for Proper Periconceptional Folate Supplementation

“…NTDs (Neural tube defects) are a group of severe, disabling and deadly congenital disorders of the nervous system, arising from incomplete neural tube closure during early stages of pregnancy [28][29][30]. Anencephaly, SB (spina bifida), encephalocele, craniorachischisis and iniencephaly are the most common [31][32][33].…”