Zampieri Bruna Lancia, Biselli Joice Matos, Goloni-Bertollo Eny Maria, Pavarino Erika Cristina
Department of Biologia Molecular, Faculdade de Medicina de São José do Rio Preto (FAMERP), Unidade de Pesquisa em Genética e Biologia Molecular (UPGEM), São José do Rio Preto, SP, Brazil.
Genet Test Mol Biomarkers. 2012 Jun;16(6):628-31. doi: 10.1089/gtmb.2011.0257. Epub 2012 Feb 17.
Mechanisms underlying meiotic nondisjunction are poorly understood. Attempts to elucidate the causes of Down syndrome (DS) have analyzed the relationship between polymorphism in folate metabolism and DS.
The role of methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) G1958A and betaine-homocysteine methyltransferase (BHMT) G742A polymorphisms in DS risk was investigated.
Blood samples were collected from a total of 86 DS mothers and from 161 control mothers. The investigation of the MTHFD1 G1958A polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and by real-time PCR for the BHMT G742A polymorphism.
The median maternal age of case mothers (30.40; 12.9-46.3 years) was significantly higher (p<0.0005) than in the control group (26.60; 15.4-57.9 years). The frequency of BHMT variant genotypes was significantly lower in DS mothers compared with controls (p=0.047). A significant decreased risk for BHMT 742 AA genotype (odds ratio [OR]=0.30; 95% confidence interval [CI]: 0.10-0.93; p=0.037) was observed. Moreover, when the dominant model was applied (BHMT 742GA or 7428AA versus 742GG), there was also a significant decrease in DS risk (OR=0.58; 95% CI: 0.37-0.98; p=0.042). MTHFD1 G1958A genotype frequencies were not significantly altered in DS mothers (p=0.206).
Our study suggests that the polymorphism BHMT G742A may modulate the DS risk in Brazilian mothers.
减数分裂不分离的潜在机制尚不清楚。为阐明唐氏综合征（DS）的病因，已有研究分析了叶酸代谢多态性与DS之间的关系。
研究亚甲基四氢叶酸脱氢酶1（MTHFD1）G1958A和甜菜碱-同型半胱氨酸甲基转移酶（BHMT）G742A多态性在DS风险中的作用。
共采集了86例DS母亲和161例对照母亲的血样。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）检测MTHFD1 G1958A多态性，采用实时PCR检测BHMT G742A多态性。
病例组母亲的中位年龄（30.40岁；12.9 - 46.3岁）显著高于对照组（26.60岁；15.4 - 57.9岁）（p<0.0005）。与对照组相比，DS母亲中BHMT变异基因型的频率显著降低（p = 0.047）。观察到BHMT 742 AA基因型的风险显著降低（比值比[OR]=0.30；95%置信区间[CI]：0.10 - 0.93；p = 0.037）。此外，当采用显性模型（BHMT 742GA或742AA与742GG）时，DS风险也显著降低（OR = 0.58；95% CI：0.37 - 0.98；p = 0.042）。DS母亲中MTHFD1 G1958A基因型频率无显著改变（p = 0.206）。
我们的研究表明，BHMT G742A多态性可能调节巴西母亲的DS风险。
