Cyril Cyrus, Rai Padmalatha, Chandra N, Gopinath P M, Satyamoorthy K
Department of Genetics, Dr. ALMPGIBMS, University of Madras, Taramani, Chennai - 600 113, India.
Indian J Hum Genet. 2009 May;15(2):60-4. doi: 10.4103/0971-6866.55217.
The 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphisms and low folate levels are associated with inhibition of DNA methyltransferase and consequently DNA hypomethylation. The expanding spectrum of common conditions linked with MTHFR polymorphisms includes certain adverse birth outcome, pregnancy complications, cancers, adult cardiovascular diseases and psychiatric disorders, with several of these associations remaining still controversial. Trisomy 21 or Down syndrome (DS) is the most common genetic cause of mental retardation. It stems predominantly from the failure of chromosome 21 to segregate normally during meiosis. Despite substantial research, the molecular mechanisms underlying non-disjunction leading to trisomy 21 are poorly understood.
Two common variants C677T and A1298C of the MTHFR gene were screened in 36 parents with DS children and 60 healthy couples from Tamil Nadu and Karnataka. The MTHFR genotypes were studied by RFLP analysis of PCR-amplified products and confirmed by sequencing.
The CT genotype was seen in three each (8.3%) of case mothers and fathers. One case father showed TT genotype. All the control individuals exhibited the wild type CC genotype. A similar frequency for the uncommon allele C of the second polymorphism was recorded in case mothers (0.35) and fathers (0.37) in comparison with the control mothers (0.39) and fathers (0.37).
This first report on MTHFR C677T and A1298C polymorphisms in trisomy 21 parents from south Indian population revealed that MTHFR 677CT polymorphism was associated with a risk for Down syndrome.
5,10 - 亚甲基四氢叶酸还原酶（MTHFR）基因多态性和低叶酸水平与DNA甲基转移酶的抑制相关，进而导致DNA低甲基化。与MTHFR基因多态性相关的常见疾病谱不断扩大，包括某些不良出生结局、妊娠并发症、癌症、成人心血管疾病和精神障碍，其中一些关联仍存在争议。21三体综合征或唐氏综合征（DS）是智力发育迟缓最常见的遗传原因。它主要源于减数分裂期间21号染色体不能正常分离。尽管进行了大量研究，但导致21三体的不分离背后的分子机制仍知之甚少。
在来自泰米尔纳德邦和卡纳塔克邦的36对患有唐氏综合征孩子的父母和60对健康夫妇中筛查了MTHFR基因的两种常见变异C677T和A1298C。通过对PCR扩增产物的限制性片段长度多态性分析研究MTHFR基因型，并通过测序进行确认。
病例组母亲和父亲中各有三人（8.3%）表现为CT基因型。一名病例组父亲表现为TT基因型。所有对照组个体均表现为野生型CC基因型。与对照组母亲（0.39）和父亲（0.37）相比，病例组母亲（0.35）和父亲（0.37）中第二种多态性罕见等位基因C的频率相似。
这份关于印度南部人群21三体综合征父母中MTHFR C677T和A1298C基因多态性的首次报告显示，MTHFR 677CT多态性与唐氏综合征风险相关。
