蛋氨酸合酶基因A2756G位点多态性与非综合征型唇腭裂的关联性研究

No association of the A2756G polymorphism of methionine synthase gene with nonsyndromic cleft lip with or without cleft palate

目的研究蛋氨酸合酶基因（methionine synthase，MS）A2756G位点多态性与非综合征型唇腭裂（nonsyndromic cleft lip with or without cleft palate，NSCL／P）的关联性。方法采用PCR-限制性片段长度多态性技术检测97个NSCL／P病例组核心家庭和104个对照家庭的MS基因A2756G位点的多态性；用人群关联研究分析、病例组核心家庭的传递不平衡检测（transmission disequilibrium test，TDT）、单体型的相对危险度分析（haplotype-based haplotype relative risk，HHRR）、家庭为基础的关联研究（family-based association tests，FBAT）等统计分析。结果子代、父亲、母亲病例组和对照组之间基因型和等位基因的分布差异均无统计学意义（P〉0．05）；本研究中在子代和母亲组中未检出GG基因型，AG基因型相对于AA基因型的比值比0R和95％c1分别为子代1．78（0．74～4．34）、父亲0．80（0．36～1．79）、母亲1．26（0．54～2．93），G相对于A基因的0R和95％CI分别为子代1．70（0．78～3．73）、父亲0．88（0．49～1．75）、母亲1．23（0．59～2．60），携带有突变基因G并不能增加患NSCL／P的危险。病例组核心家庭分析，TDT分析χ^2=0．034，P〉0．05；HHRR分析χ^2=0．03，P〉0．05；FBAT分析Z=0．186，P〉0．05。结论结果未显示出MS基因A2756G位点多态性和NSCL／P发生的相关性，还待进一步研究。

Objective To study the association of the A2756G polymorphism of the methionine synthase （MS） gene with nonsyndromic cleft lip with or without cleft palate （NSCL/P） in Chinese. Methods Ninety-seven NSCL/P case-parent triads were selected as the case group. One hundred and four healthy subjects and their biological parents were selected as control group. For all subjects the A2756G polymorphism of the MS gene was examined by PCR-RFLP method. Results There was no statistical difference in genotype and allele frequencies for MS A2756G variants among family members between case group and control group. The GG genotype was not detected in the offsprings and mothers. The odds ratio and confidence interval of genotype AG in offspring, father and mother were 1.78（0.74-4.34）, 0.80（0.36- 1.79） and 1.26（0.54-2. 93） respectively. The odds ratio and confidence interval of allele G in offspring, father and mother were 1.70（0.78-3.73）, 0. 88（0. 49-1.75）, and 1.23（0.59-2.60） respectively. The G allele did not increase the risk of NSCL/P. Transmission disequilibrium test （TDT） analysis yielded no evidence of linkage disequilibrium （χ^2=0. 034 ,P〉0.05）. The results of haplotype-based haplotype relative risk （HHRR） analysis （χ^2=0.03,P〉0.05） and family-based association tests （FBAT） （Z=0. 186, P〉 0.05） failed to show association between the MS A2756G variant and the risk of NSCL/P. Conclusion The A2756G polymorphism of the MS gene was not associated with NSCL/P in Chinese in the present study.