ABCB1基因多态性与中国骨髓移植患者服用环孢素A所致移植后糖尿病的关联分析

Correlation between ABCB1 polymorphisms and the susceptibility of post-transplant diabetes mellitus induced by cyclosporine A in Chinese bone marrow transplant recipients

目的分析中国骨髓移植患者ABCB1基因型的分布特征及其多态性与中国骨髓移植患者服用环孢素A所致移植后糖尿病的相关性。方法选取中国骨髓移植患者112例为研究对象,其中血糖正常97例和移植后糖尿病15例。用聚合酶链式反应直接测序的方法检测ABCB1各位点的基因型分布及等位基因频率。结果中国骨髓移植患者ABCB1 C1236T、G2677T/A、C3435T基因型分布均符合Hardy-Weinberg平衡。ABCB1 C1236T中移植后糖尿病组和血糖正常组的CC基因型分别为6.67%,14.43%;CT基因型分别为53.33%,45.36%;TT基因型分别为40.00%,40.21%;C等位基因分别为33.33%,37.11%;T等位基因分别为66.67%,62.89%,差异均无统计学意义(P>0.05)。ABCB1G2677T/A中移植后糖尿病组和血糖正常组的GG基因型分别为13.33%,9.28%;AG/GT基因型分别为60.00%,52.58%;AA/AT/TT基因型分别为26.67%,38.14%;G等位基因分别为43.33%,35.57%;A/T等位基因分别为56.67%,64.43%,差异均无统计学意义(P>0.05)。ABCB1 C3435T中移植后糖尿病组和血糖正常组的CC基因型分别为40.00%,36.08%;CT基因型分别为46.67%,43.30%;TT基因型分别为13.33%,20.62%;C等位基因分别为63.33%,57.73%;T等位基因分别为36.67%,42.27%,差异均无统计学意义(P>0.05)。结论 ABCB1多态性与中国骨髓移植患者服用环孢素A所致的移植后糖尿病不相关,但仍不能忽视ABCB1基因多态性对环孢素A药效和药物不良反应的影响。

Objective To study the frequency distribution patterns of ABCB1 polymorphisms in Chinese bone marrow transplant recipients,to explore the correlation between ABCB1 polymorphisms and the susceptibility of post-transplant diabetes mellitus（PTDM） induced by cyclosporine A（Cs A） in Chinese bone marrow transplant recipients.Methods We totally collect 112 cases of Chinese bone marrow transplant recipients,97 cases with normal blood glucose（NBG） and 15 cases with PTDM.Polymerase chain reaction-direct sequencing methods were used to detect the genotype of ABCB1.Results The distribution of genotypic and allelic frequencies of ABCB1 C1236 T,G2677T/A and C3435 T were all consistent with Hardy-Weinberg balances（P 0.05）.In PTDM and NBG patients,the CC genotypic frequencies of ABCB1 C1236 were 6.67% and 14.43%;the CT were 53.33% and 45.36%;the TT were 40.00% and 40.21%,respectively;the C allelic frequencies of ABCB1 C1236 were 33.33% and 37.11%;the T were 66.67% and 62.89%,respectively.The GG genotypic frequencies of ABCB1 G2677 T/A were 13.33% and 9.28%;the AG/GT were 60.00% and 52.28%;the AA/AT/TT were 26.67% and 38.14%,respectively;the G allelic frequencies of ABCB1 G2677 T/A were 43.33% and 35.57%;the A/T were 56.67% and 64.43%,respectively.The CC genotypic frequencies of ABCB1 C3435 T were 40.00% and36.08%;the CT were 46.67% and 43.30%;the TT were 13.33% and 20.62%,respectively;the C allelic frequencies of ABCB1 C3435 T were 63.33% and 57.73%;the T were 36.67% and 42.27%,respectively.There was no significant difference in the distribution of allele and genotype of ABCB1 C1236 T,G2677T/A and C3435 T between the PTDM and NBG patients（P 0.05）.Conclusion The polymorphisms of ABCB1 is not correlated to the susceptibility of post-transplant diabetes mellitus by Cs A.But,we still need to pay much attention to the correlation between effect and adverse reaction of Cs A and polymorphism of ABCB1.