Oliveira Kelly C, Verreschi Ieda T N, Sugawara Eduardo K, Silva Vanessa C, Galera Bianca B, Galera Marcial Francis, Bianco Bianca, Lipay Monica V N
Division of Endocrinology, Department of Medicine, Universidade Federal de São Paulo, São Paulo, Brazil.
Genet Test Mol Biomarkers. 2012 May;16(5):396-400. doi: 10.1089/gtmb.2011.0222. Epub 2012 Jan 27.
To determine the frequency of C677T and A1298C polymorphisms of the MTHFR gene and correlate them with homocysteine serum levels in patients with Turner syndrome (TS) and controls.
This case-control study included 78 women with TS and a control group of 372 healthy individuals without personal or family history of cardiovascular disease and cancer. C677T (rs1801133) and A1298C (rs1801131) polymorphisms were detected by polymerase chain reaction-restriction fragment-length polymorphism and the TaqMan system, respectively. Homocysteine serum levels were determined by high-performance liquid chromatography. The results were analyzed statistically, and p<0.05 was considered to represent a significant difference.
The homocysteine levels change was 13.9+3.3 nM in patients with TS and 8.8+3.2 nM in the control group. No significant difference between groups was found (p=0.348). Single-marker analysis revealed no association between MTHFR C677T polymorphism and TS when genotype (p=0.063) or allelic (p=0.277) distribution was considered. Regarding MTHFR A1298C polymorphism, a statistical difference was found between the TS group and the control group, for both genotype (p<0.0001) and allele (p<0.0001) distribution. Haplotype analysis of 2 MTHFR polymorphisms identified 2 haplotypes-CC and TC-associated with TS (p<0.001 and p=0.0165, respectively). However, homocysteine levels were not higher in patients with haplotype risk.
The results suggest that the C677T and A1298C polymorphisms of the MTHFR gene are not related to homocysteine levels in Brazilian patients with TS, despite the differential distribution of the mutated allele C (A1298C) in these patients. Further studies are needed to investigate the possible genetic interaction with homocysteine levels in TS.
确定特纳综合征（TS）患者及对照组中甲基四氢叶酸还原酶（MTHFR）基因C677T和A1298C多态性的频率，并将其与血清同型半胱氨酸水平相关联。
这项病例对照研究纳入了78例TS女性患者以及一个由372名无心血管疾病和癌症个人或家族史的健康个体组成的对照组。分别采用聚合酶链反应-限制性片段长度多态性方法和TaqMan系统检测C677T（rs1801133）和A1298C（rs1801131）多态性。通过高效液相色谱法测定血清同型半胱氨酸水平。对结果进行统计学分析，p<0.05被认为具有显著差异。
TS患者的同型半胱氨酸水平变化为13.9+3.3 nM，对照组为8.8+3.2 nM。两组之间未发现显著差异（p=0.348）。单标记分析显示，在考虑基因型（p=0.063）或等位基因（p=0.277）分布时，MTHFR C677T多态性与TS之间无关联。关于MTHFR A1298C多态性，在TS组和对照组之间，基因型（p<0.0001）和等位基因（p<0.0001）分布均存在统计学差异。对2种MTHFR多态性进行单倍型分析，确定了2种与TS相关的单倍型——CC和TC（分别为p<0.001和p=0.0165）。然而，具有单倍型风险的患者的同型半胱氨酸水平并不更高。
结果表明，尽管巴西TS患者中突变等位基因C（A1298C）的分布存在差异，但MTHFR基因的C677T和A1298C多态性与TS患者的同型半胱氨酸水平无关。需要进一步研究来调查TS中与同型半胱氨酸水平可能存在的基因相互作用。
