Noori Noormohammad, Miri-Moghaddam Ebrahim, Dejkam Asieh, Garmie Yasman, Bazi Ali
Department of Pediatric Cardiology, Children and Adolescents Health Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.
Genetics of Non-Communicable Disease Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.
Caspian J Intern Med. 2017 Spring;8(2):83-90. doi: 10.22088/cjim.8.2.83.
The 5, 10-methyleneterahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) are two essential enzymes involved in folate metabolism. The relationship between genetic polymorphisms and congenital heart defects (CHDs) is inconsistent. Our aim was to investigate the association between two well-known polymorphisms of MTHFR and MTRR genes, C677T and A66G, respectively, and CHDs in Iranian patients.
We enrolled 74 patients with ventricular septal defect (VSD) and 79 with tetralogy of fallot (TOF) along with 147 healthy controls. C677T and A66G polymorphisms were detected using tetra-primer ARMS (amplification refractory mutation system) PCR.
Individuals carrying homozygote mutant (TT) genotype of C677T polymorphism represented the highest risk for CHDs (OR=7.3, 95% CI: 0.8-61, P=0.06). Also, significantly increased risk of VSD was observed in individuals with TT genotype (OR=10, 95% CI: 1-92.2, P=0.04). However, the frequency for variant allele (T) of C677T polymorphism was not statistically different between cases and controls (16.3% and 20.9%, respectively). For A66G polymorphism, we found that AG and GG genotypes had higher frequencies in the patients (48.4% and 21.6% respectively) than controls (42.9% and 15.6%, respectively). In line with this, combined AG+GG genotype represented with significantly elevated risk of CHDs (OR=1.6; 95% CI: 1-2.6, P=0.03). AG+GG combination was also identified as a risk factor for TOF (OR=1.8, 95% CI: 1-3.3, P=0.04).
We demonstrated that C677T polymorphism of MTHFR gene was significantly associated with VSD in our patients. Our study also suggested that A66G polymorphism of MTRR gene may contribute to the development of TOF in Iranians.
5,10 - 亚甲基四氢叶酸还原酶（MTHFR）和蛋氨酸合成酶还原酶（MTRR）是参与叶酸代谢的两种关键酶。基因多态性与先天性心脏病（CHD）之间的关系并不一致。我们的目的是研究伊朗患者中MTHFR和MTRR基因的两种著名多态性，即分别为C677T和A66G，与先天性心脏病之间的关联。
我们纳入了74例室间隔缺损（VSD）患者、79例法洛四联症（TOF）患者以及147名健康对照者。使用四引物ARMS（扩增阻滞突变系统）PCR检测C677T和A66G多态性。
携带C677T多态性纯合突变（TT）基因型的个体患先天性心脏病的风险最高（OR = 7.3，95%CI：0.8 - 61，P = 0.06）。此外，TT基因型个体患室间隔缺损的风险显著增加（OR = 10，95%CI：1 - 92.2，P = 0.04）。然而，C677T多态性变异等位基因（T）的频率在病例组和对照组之间无统计学差异（分别为
16.3%和20.9%）。对于A66G多态性，我们发现患者中AG和GG基因型的频率（分别为48.4%和21.6%）高于对照组（分别为42.9%和15.6%）。与此一致，AG + GG组合基因型患先天性心脏病的风险显著升高（OR = 1.6；95%CI：1 - 2.6，P = 0.03）。AG + GG组合也被确定为法洛四联症的一个危险因素（OR = 1.8，95%CI：1 - 3.3，P = 0.04）。
我们证明MTHFR基因的C677T多态性与我们患者中的室间隔缺损显著相关。我们的研究还表明MTRR基因的A66G多态性可能与伊朗人法洛四联症的发生有关。
