Prevalence of the polymorphism MTHFR A1298C and not MTHFR C677T is related to chromosomal aneuploidy in Brazilian Turner Syndrome patients

Abstract

Background: Dysfunctions in the folate metabolism can result in DNA hypomethylation and abnormal chromosome segregation. Two common polymorphisms of this enzyme (C677T and A1298C) reduce its activity, but when associated with aneuploidy studies the results are confl icting. The objective of the present study is to analyze the MTHFR gene polymorphisms in women with Turner Syndrome and in a control group, correlating the fi ndings to the chromosomal aneuploidy. Methods: The study comprised 140 patients with Turner Syndrome, of which 36 with chromosome mosaicism and 104 nonmosaics, and a control group of 209 fertile and healthy women without a history of any offspring with aneuploidy. Polymorphisms C677T and A1298C were studied by RFLP-PCR and the results were statistically analyzed. Results: The frequency of genotypes MTHFR 677CC, 677CT and 677TT in the patients with Turner Syndrome and chromosome mosaicism was, respectively, 58.3%, 38.9% and 2.8%. Among the patients with non-mosaic Turner Syndrome, 47.1% presented genotype 677CC, 45.2% genotype 677CT, and 7.7% genotype 677TT. Among the 209 individuals of the control group, genotypes 677CC, 677CT and 677TT were found at the following frequencies: 48.3%, 42.1% and 9.6%, respectively. As for polymorphism A1298C, the patients with Turner

Genetic Variants Involved in One-Carbon Metabolism: Polymorphism Frequencies and Differences in Homocysteine Concentrations in the Folic Acid Fortification Era

“…Herein, we observed that 11.3% of the population presented as being homozygous (TT) for the variant 677C>T, considering a homozygote prevalence of 13.2% and 1.6% among White and Black races, respectively. In a study concerning the polymorphism 1298A>C, 40% heterozygotes (AC) and 6% mutant homozygotes CC were observed in a healthy Brazilian population [21], consistent with the results of the present study (34.2% AC and 6.2% CC). In the United Kingdom, 44.8% heterozygotes AC and 9.3% mutant homozygotes CC were observed in an elderly population ( n = 1041) [22].…”

Abnormal Folate Metabolism and Maternal Risk for Down Syndrome

“…The MTHFR 677 C→T polymorphism is associated with diminished levels of 5-methylcytosine and DNA hypomethylation (Chen et al, 2010;Friso et al, 2002;Paz et al, 2002), micronucleus formation (Andreassi et al, 2003;Botto et al, 2003), and microsatellite instability (Naghibalhossaini et al, 2010) in the presence of the variant T allele. The homozygous variant genotype of another polymorphism of the MTHFR gene, 1298 A→C, was more frequent in patients with Turner syndrome (de Oliveira et al, 2008), and a higher frequency of the C allele was observed in spontaneous abortions with fetal chromosomal aneuploidy as compared to those with normal fetal karyotypes (Kim et al, 2011), suggesting its involvement in the origin of chromosomal imbalances. The MTR 2756 A→G polymorphism was associated with reduced number of hypermethylated CpG islands of suppressor tumor genes and with higher micronucleus rates in the presence of the MTRR 66 GG variant genotype (Botto et al, 2003;Paz et al, 2002;Zijno et al, 2003).…”

Polymorphisms in folate pathway genes are not associated with somatic nondisjunction in turner syndrome

“…TS is characterized by the absence or abnormality of one sex chromosome in either all or some cells. To date, two studies have evaluated the influence of two common MTHFR polymorphisms (677C>T and 1298A>C) and nondisjunction in Turner syndrome, and have reported conflicting results [Santos et al, 2006;Oliveira et al, 2008]. Therefore, virtually every live-born TS individual must comprise more than one cell line, thus constituting a mosaic [Oliveira et al, 2009;Hook and Warburton, 2014].…”

“…Therefore, virtually every live-born TS individual must comprise more than one cell line, thus constituting a mosaic [Oliveira et al, 2009;Hook and Warburton, 2014]. To date, two studies have evaluated the influence of two common MTHFR polymorphisms (677C>T and 1298A>C) and nondisjunction in Turner syndrome, and have reported conflicting results [Santos et al, 2006;Oliveira et al, 2008].…”