神经管发育不良患儿及其核心家庭MTHFR基因A1298C多态性分布的研究

The genetic polymorphism distribution of A1298c nucleotide of MTHFR in patients with NDTs and its nucleus families

目的 通过对神经管发育不良 (NDTs)患儿及核心家庭MTHFR基因A1 2 98位点多态性分布的研究 ,探讨该基因多态性与NDTs之间的关系。方法 2 0 0 0年 9月～ 2 0 0 2年 3月 ,40例 3～ 1 5岁NDTs患儿 (男 2 8例 ,女 1 2例 )及其中 2 6个核心家庭进行研究。应用聚合酶链反应 限制性片段长度多态性分析 (PCR RFLP)技术 ,分析MTHFR基因第 1 2 98位核苷酸基因型 (野生型、杂合型、突变纯合型 )的分布情况 ;并对 2 6个核心家庭进行以父母为对照的病例对照研究 ,计算传递失衡指数 (TDT)及基于单体型的单体型相对危险度 (HHRR)。结果 NDTs患儿、核心家庭与正常对照中均未发现纯合突变。基因型构成比采用 χ2 检验 ,NDTs患儿及患儿母亲野生型分别占 1 7.50 % ,1 1 .54 % ,杂合型分别占 82 .50 % ,88.46 % ,与正常对照之间差异无显著性意义 (分别为P >0 .2 5 ;P>0 .90 )。患儿父亲野生型占 30 .77% ,杂合突变型占 69.2 3 % ,低于正常对照 (P <0 .0 5)。等位基因频率比较采用u检验 ,患儿为 41 .2 5 % ,与对照间差异无显著性意义 (P >0 .0 5) ;患儿父母分别为69 .2 3 % ,88.46 % ,均高于正常对照 (P <0 .0 1 )。核心家庭分析结果 :TDT(χ2 ) =0 .36 ,P >0 .0 5 ;HHRR(χ2 ) =0 .369,P >0 .0 5。结论 MTHFR基因第 1

Objective To examine the relationship b etween the genetic polymorphism of MTHFR A1298C and neural tube defects. Methods Forty cases (28 males and 12 females) aged 3～15 years and 26 nucleus families were studied between September 2000 and March 200 2 . Using PCR-RFLP to detect the genotypes of the 1298th nucleotide including wil d type, heterozygate type and mutant homozygote type of MTHFR, 26 nuclear famil ies were analyzed as case-parental control study, from which Transmitted Disequ ilibrium Test (TDT) and Haplotype-based Haplotype Relative Risk(HHRR) were calc ulated. Results It showed no mutant homozygotes among the pati ents and the mothers and the controls. The ratios of genotypes showed no differe nce in the patients and control groups or in mothers and the controls. The wild type of NDTs patients and mothers were 17.5% and 11.54% respectively. T he heterozygate type of NDTs patients and mothers were 82.50% and 88.46% respectively without difference between the controls groups ( χ 2-test, P > 0.25 , P > 0.90 respectively).The proportion of wild type and mutant homozygote type was 30.77% and 69.23% respectively in the fathers, and i t was lower than that in the controls ( χ 2-test, P < 0.05 ).The allel e frequency of the 1298C was no different between the patients and the controls( u-test, P > 0.05 ). It was higher in the parents than that in the controls (u-test, P < 0.01 ). Nuclear families analysis demonstrated TDT (χ 2)= 0.36 , P > 0.05 and HHRR ( χ 2)= 0.369 , P > 0.05 respecti vely.Conclusions There are no difference in patients with neur a l tube defects and the control groups in genetic polymorphism distribution of th e 1298th nucleotide of MTHFR. There is no transmitted disquilibrium of the allel e 1298C in NDTs nucleus families. It seems to be no direct relation between the genetic polymorphism of MTHFR A 1298C and neural tube defects in our country.