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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 analyze the distribution and polymorphism of ABCB1 genotype in Chinese patients with bone marrow transplantation and the correlation between the polymorphism of ABCB1 genotype and the post-transplant diabetes mellitus induced by CsA in Chinese patients with bone marrow transplantation. Methods One hundred and twelve patients with bone marrow transplantation in China were selected as study subjects, including 97 cases of normal blood glucose and 15 cases of post-transplant diabetes mellitus. The genotype distribution and allele frequencies of each site of ABCB1 were detected by polymerase chain reaction sequencing. Results The distribution of ABCB1 C1236T, G2677T / A and C3435T genotypes in China’s bone marrow transplantation patients were in accordance with Hardy-Weinberg equilibrium. The CC genotypes in ABCB1 C1236T group and normal glucose group were 6.67% and 14.43% respectively; the CT genotypes were 53.33% and 45.36% respectively; the TT genotypes were 40.00% and 40.21% respectively; the C alleles were 33.33% and 37.11%, respectively. The T allele was 66.67% and 62.89% respectively, with no significant difference (P> 0.05). The GG genotypes of ABCB1G2677T / A in diabetic group and normal glucose group were 13.33% and 9.28%, AG / GT genotype were 60.00% and 52.58%, respectively. The genotypes of AA / AT / TT were 26.67% and 38.14 %. The G allele was 43.33% and 35.57% respectively. The A / T allele was 56.67% and 64.43% respectively, with no significant difference (P> 0.05). CC genotypes in ABCB1 C3435T group and normal blood glucose group were 40.00% and 36.08% respectively; CT genotypes were 46.67% and 43.30% respectively; TT genotypes were 13.33% and 20.62% respectively; C alleles were 63.33% and 57.73%, respectively. The T allele was 36.67% and 42.27% respectively, with no significant difference (P> 0.05). Conclusion ABCB1 polymorphism is not associated with posttransplant diabetes mellitus induced by cyclosporin A in Chinese patients with bone marrow transplantation. However, the effects of ABCB1 gene polymorphism on the efficacy and adverse drug reactions of cyclosporin A can not be ignored.