Mohamed Sa'dom Siti Aisyah Faten, Hashim Hashima, Maran Sathiya, Mohd Zain Mohd Rizal, Wan Ibrahim Wan Pauzi, Wong Abdul Rahim, Corno Antonio F, Wan Taib Wan Rohani, Tan Huay Lin
Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia 16150 Kubang Kerian, Kelantan, Malaysia.
Department of Pediatrics Medicine, School of Medical Sciences, Universiti Sains Malaysia 16150 Kubang Kerian, Kelantan, Malaysia.
Am J Cardiovasc Dis. 2016 Nov 30;6(4):138-145. eCollection 2016.
Ventricular septal defect (VSD) is the most common form of cardiac malformations accounting approximately 20% of all congenital heart defects. is an inhibitory protein that antagonizes the signalling of TGF-β family member and has been found in the development and function of mouse heart models. This study aims to screen and identify the polymorphisms of exonic regions in Malay population with VSD. Peripheral blood samples were collected and extracted from 30 clinically diagnosed VSD patients. PCR amplification was performed using 12 sets of designed primers encompassing seven exons of . Re-sequencing was conducted to characterize the polymorphisms of . Observed polymorphisms were then genotyped in 30 healthy individuals using both re-sequencing and allele-specific PCR techniques. A total of 10 variants were identified in the patient population located in the upstream (rs7236774), exonic (rs368427729, rs145686330, rs3764482, rs3809922, rs780863704 and rs3809923), intronic (rs3736242) and 3'UTR regions (rs375444823 and rs16950113). No significant difference of genotype and allele frequency was observed among these SNPs. Two synonymous variants (rs3809922 and rs3809923) were found in complete linkage disequilibrium (r=1.0) with each other indicate a strong correlation of these SNPs. The identification of these SNPs provides a new perspective of the VSD causation.
室间隔缺损（VSD）是最常见的心脏畸形形式，约占所有先天性心脏病的20%。[某蛋白]是一种抑制蛋白，可拮抗转化生长因子-β家族成员的信号传导，已在小鼠心脏模型的发育和功能中被发现。本研究旨在筛选和鉴定马来西亚VSD人群中外显子区域的多态性。收集并提取了30例临床诊断为VSD患者的外周血样本。使用涵盖[某基因]七个外显子的12组设计引物进行PCR扩增。进行重测序以表征[某基因]的多态性。然后使用重测序和等位基因特异性PCR技术对30名健康个体中的观察到的多态性进行基因分型。在患者群体中总共鉴定出10个变体，分别位于上游（rs7236774）、外显子（rs368427729、rs145686330、rs3764482、rs3809922、rs780863704和rs3809923）、内含子（rs3736242）和3'UTR区域（rs375444823和rs16950113）。在这些单核苷酸多态性中未观察到基因型和等位基因频率的显著差异。发现两个同义变体（rs3809922和rs3809923）处于完全连锁不平衡状态（r = 1.0），表明这些单核苷酸多态性之间存在强相关性。这些单核苷酸多态性的鉴定为VSD的病因提供了新的视角。
