多态性MTHFR A1298C而非MTHFR C677T的患病率与巴西特纳综合征患者的染色体非整倍性有关。

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

作者信息

Oliveira Kelly Cristina de, Bianco Bianca, Verreschi Ieda T N, Guedes Alexis Dourado, Galera Bianca Borsato, Galera Marcial Francis, Barbosa Caio P, Lipay Monica Vannucci Nunes

机构信息

Department of Medicine, Federal University of São Paulo, SP, Brazil.

出版信息

Arq Bras Endocrinol Metabol. 2008 Nov;52(8):1374-81. doi: 10.1590/s0004-27302008000800028.

DOI:10.1590/s0004-27302008000800028

PMID:19169497

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 conflicting. 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 findings to the chromosomal aneuploidy.

METHODS

The study comprised 140 patients with Turner Syndrome, of which 36 with chromosome mosaicism and 104 non-mosaics, 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 Syndrome and chromosome mosaicism presented genotypes 1298AA, 1298AC and 1298CC at the following frequencies: 58.3%, 27.8% and 13.9%, respectively. Among the non-mosaic Turner Syndrome patients, genotype 1298AA was found in 36.5%, genotype 1298AC in 39.4%, and genotype 1298CC in 22.1%. In the control group, genotypes 1298AA, 1298AC and 1298CC were present at the following frequencies: 52.6%, 40.7% and 6.7%, respectively.

CONCLUSION

No correlation was observed between the MTHFR gene polymorphism 677 and chromosomal aneuploidy in the Turner Syndrome patients. However, the MTHFR gene polymorphism at position 1298, mainly genotype 1298CC that reduces the enzyme efficiency, was more frequent in the group of Turner Syndrome patients, suggesting its involvement in mechanisms related to chromosomal imbalances.

摘要

背景

叶酸代谢功能障碍可导致DNA低甲基化和染色体异常分离。该酶的两种常见多态性（C677T和A1298C）会降低其活性，但在与非整倍体研究相关时，结果存在冲突。本研究的目的是分析特纳综合征女性和对照组中MTHFR基因多态性，并将研究结果与染色体非整倍体相关联。

方法

该研究纳入了140例特纳综合征患者，其中36例为染色体嵌合体，104例为非嵌合体，以及一个由209名有生育能力且健康、无任何非整倍体后代病史的女性组成的对照组。通过限制性片段长度多态性聚合酶链反应（RFLP-PCR）研究C677T和A1298C多态性，并对结果进行统计学分析。

结果

特纳综合征和染色体嵌合体患者中MTHFR 677CC、677CT和677TT基因型的频率分别为58.3%、38.9%和2.8%。在非嵌合型特纳综合征患者中，47.1%表现为677CC基因型，45.2%为677CT基因型，7.7%为677TT基因型。在对照组的209名个体中，677CC、677CT和677TT基因型的频率分别为48.3%、42.1%和9.6%。至于A1298C多态性，特纳综合征和染色体嵌合体患者中1298AA、1298AC和1298CC基因型的频率分别为58.3%、27.8%和13.9%。在非嵌合型特纳综合征患者中，1298AA基因型的比例为36.5%，1298AC基因型为39.4%，1298CC基因型为22.1%。在对照组中，1298AA、1298AC和1298CC基因型的频率分别为52.6%、40.7%和6.7%。