还原叶酸载体1基因A80G多态性与非综合征型唇腭裂的相关性研究

Relationship between genetic polymorphisms of RFC1 A80G and nonsymdromic cleft lip with or without palate

目的探讨还原叶酸载体(RFC)1基因A80G多态性与非综合症型唇腭裂(NSCL/P)相关性。方法收集97个核心家庭和104个对照家庭,用聚合酶链式反应-限制性片段长度多态性方法,进行RFC1基因A80G位点多态性检测,用人群关联研究分析、NSCL/P核心家庭的TDT、HHRR、FBAT等检验统计分析。结果人群关联研究分析,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无显著性(P>0.05)。AG基因型相对于AA基因型的比值比OR(95%CI)、P值分别为子代0.87(0.44～1.70)、0.657;父亲1.09(0.54～2.21)、0.788;母亲1.63(0.79～3.36)、0.152。GG基因型相对于AA基因型的OR(95%CI)、P值分别为子代0.48(0.19～1.23)、0.094;父亲0.93(0.38～2.23)、0.850;母亲1.30(0.46～3.67)、0.584。G基因相对于A基因的OR(95%CI)、P值分别为子代1.22(0.78～1.94)、0.386;父亲1.02(0.64～1.61)、0.945;母亲0.91(0.58～1.41)、0.660。携带有突变基因G并不能增加患NSCL/P的危险。NSCL/P核心家庭分析,TDT检验中传递G等位基因给患病子代的为40次,传递A等位基因的为71次,等位基因A比突变等位基因G更易传递给患病子代(χ2=8.658,P<0.05;HHRR检验χ2=10.31,P<0.05;FBAT检验Z=2.942,P<0.05)。结论利用核心家庭资料进行统计分析的结果则认为RFC1基因A80G位点变异存在传递不平衡现象,这与NSCL/P发病危险之间存在有一定的关联关系,等位基因A可能与NSCL/P的高危显性有关系。

Objective To explore the relationship between genetic polymorphisms of reduced folate carrier (RFC)1 A80G and nonsymdromic cleft lip with or without palate on Chinese population.Methods There were 97 NSCL/P case-parent triads those were selected as case group. At the same period, 104 healthy subjects were selected together with their biological parents as control group. For all subjects the polymorphisms of RFC1 A80G were examined by PCR-RFLP method.Results There was no statistical difference in genotype and gene frequencies for RFC1A80G variants among family members between case group and control group in offsprings and fathers and mothers (P<0.05). The odds ratio(OR), confidence interval(CI) and P value of offspring, father and mother genotype (AG) were 0.87(0.44-1.70),0.657;1.09(0.54-2.21),0.788;1.63(0.79-3.36),0.152 respectively. The OR, CI and P value of offspring, father and mother allele (GG) were 0.48(0.19-1.23),0.094;0.93(0.38-2.23),0.850;1.30(0.46-3.67),0.584 respectively. The OR, CI and P value of offspring, father and mother allele (G) were 1.22(0.78-1.94),0.386;1.02(0.64-1.61),0.945;0.91(0.58-1.41),0.660.The G allele could not increase the risk of NSCL/P. But in the transmission disequilibrium test (TDT) analysis, the transmission of the G allele was 40 times, the A allele was 71 times, the A allele was more likely to transmit to the sicken offspring(χ~2=8.658,P<0.05). Results of haplotype-based haplotype relative risk (HHRR) analysis (χ~2=10.31,P<0.05) and family-based association tests (FBAT)(Z=2.942,P<0.05) were showed that there was an association between RFC1A80G variant and the risk of NSCL/P.Conclusion The statistical analysis of nuclear family could evidence of linkage in the presence of disequilibrium, there was an association between RFC1 A80G variant and the risk of NSCL/P, and the A allele could have an association with the dominant high-risk of NSCL/P.