Abdulla Riaz, Kudkuli Jagadish, Kapoor Saketh, Prabhu Vishnudas, Shetty Pushparaja, Aziz Niloufa Z
Department of Oral Pathology and Microbiology, Yenepoya Dental College, Yenepoya (Deemed to be University), Mangalore, Karnataka, India.
Department of Biomaterials and Research Centre, Yenepoya Dental College, Yenepoya (Deemed to be University), Mangalore, Karnataka, India.
J Oral Maxillofac Pathol. 2020 Sep-Dec;24(3):453-458. doi: 10.4103/jomfp.JOMFP_329_19. Epub 2021 Jan 9.
Clefts of the lip, with or without cleft palate and cleft palate only, collectively called as orofacial clefts (OFCs) are one of the most common congenital malformations with varying degrees of penetrance and phenotype expressions. The aim of this study was to investigate the association between methylenetetrahydrofolate reductase (MTHFR) cytosine-to-thymine (c. 677 C>T), adenine-to-cytosine (c.1298 A>C) single- nucleotide polymorphisms (SNPs) and South Indian patients with the nonsyndromic cleft lip with or without palate (NSCL ± P).
A cohort consisting of 25 cases of NSCL ± P and 18 controls from a South Indian cohort were included in this case-control study. Genetic analysis of c.677C>T and c.1298A C polymorphisms in the MTHFR gene was carried out using Sanger sequencing and analyzed from chromatogram profiles. Data interpretation was done using statistical software MedCalc Statistical Software version 16.2 and the Statistical Package for the Social Sciences (SPSS version 22.0).
DNA sequence analysis of the MTHFR gene revealed c. 677C>T and c. 1298A>C polymorphisms in 16% and 76% of NSCL ± P cases, respectively. Heterozygous variant in MTHFR c. 1298A>C polymorphism was found to be a significant risk factor ( = 0.0164) for NSCL ± P in South Indian ethnic population. c.677C>T polymorphism, in particular, was apparently dormant overall in the study population. These results offer certain novelty in terms of the distinctive pattern in SNPs of genotypes observed in the study.
NSCL ± P is one of the most common and challenging congenital malformations with complex etiological basis. Common risk factors such as MTHFR SNPs, namely c.677C>T and c.1298A>C, are subjected to variations in terms of ethnic group, geographic region and micro/macro-environmental factors. Overall, our study has explored part of South Indian ethnic population and revealed a different and unique distribution of mutations in this sample population.
唇裂（伴或不伴腭裂）以及单纯腭裂统称为口面部裂隙（OFCs），是最常见的先天性畸形之一，其外显率和表型表达程度各异。本研究旨在调查亚甲基四氢叶酸还原酶（MTHFR）基因胞嘧啶突变为胸腺嘧啶（c.677 C>T）、腺嘌呤突变为胞嘧啶（c.1298 A>C）的单核苷酸多态性（SNP）与南印度非综合征性唇裂伴或不伴腭裂（NSCL±P）患者之间的关联。
本病例对照研究纳入了一个由25例NSCL±P患者和18例来自南印度队列的对照组成的队列。使用桑格测序法对MTHFR基因中的c.677C>T和c.1298A C多态性进行基因分析，并从色谱图中进行分析。使用统计软件MedCalc Statistical Software版本16.2和社会科学统计软件包（SPSS版本22.0）进行数据解读。
MTHFR基因的DNA序列分析显示，分别有16%和76%的NSCL±P病例存在c.677C>T和c.1298A>C多态性。在南印度种族人群中，发现MTHFR c.1298A>C多态性的杂合变异是NSCL±P的一个显著危险因素（P = 0.0164）。特别是c.677C>T多态性在研究人群中总体上似乎处于休眠状态。这些结果在研究中观察到的基因型SNP独特模式方面具有一定的新颖性。
NSCL±P是最常见且具有挑战性的先天性畸形之一，其病因基础复杂。常见的危险因素如MTHFR SNP，即c.677C>T和c.1298A>C，会因种族、地理区域以及微观/宏观环境因素而有所不同。总体而言，我们的研究探索了部分南印度种族人群，并揭示了该样本人群中突变的不同且独特的分布情况。
