多囊卵巢综合征患者胰岛素受体基因及抵抗素基因内含子变异的研究

Variation of single nucleotide polymorphism of the insulin receptor gene and resistin gene with polycystic ovary syndrome

目的探讨胰岛素受体基因(INSR)酪氨酸激酶区17外显子多态性及抵抗素基因内含子基因多态性在多囊卵巢综合征(PCOS)发病中的作用。方法用聚合酶链反应—限制性片段多态性技术(PCR-RFLP)检测75例PCOS患者(PCOS组)和66例健康妇女(对照组)的INSR第17外显子1058位点多态性;用3100 AvantGenet-ic Analyzer测序,观察两组抵抗素基因第2内含子序列。结果PCOS组和对照组INSR第17外显子多态性出现频率分别为41.0%和12.5%(P<0.01),PCOS组非肥胖者和肥胖者分别为52.0%和25.0%(P<0.01)。PCOS组INSR第17外显子1058位点出现T和C等位基因患者的BM I分别为(22.99±3.24)kg/m2和(25.80±4.01)kg/m2(P<0.01)。两组抵抗素基因在距第2外显子末端39 bp位点上存在C和CT两种基因型,PCOS组C等位基因和CT双峰出现的频率分别为96%和4%,对照组分别为95%和5%,两组比较P>0.05。结论INSR第17外显子的多态性(C-T)可增大PCOS发病的风险,可能为PCOS的易感基因(在非肥胖者中更有意义);抵抗素基因第2内含子多态性与PCOS发病无明显相关性。

Objective To investigate the correlation of C/T single nueleotide polymorphism at 17 exon in tyrosine kinase domain of insulin receptor gene and the intron 2 of resistin gene in patients with polycystic ovary syndrome （PCOS）. Methods 75 patients with PCOS （PCOS group） and 66 normal females （control group） were selected to analyze the 1058 site single nucleotide polymorphism at 17 exon of the insulin receptor gene （INSR） with polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP）. Sequence of a single nucleotide polymorphism in the intron 2 of the resistin gene were determined by using Genetic Analyzer. Results C/T single nucleotide polymorphism frequency at the exon 17 of INSR in PCOS group was significantly higher than that in the control group （41% vs 12.5%, P 〈 0. 01 ）. There was a significant difference between the frequency in the non-obese PCOS （52%） and the obese PCOS （25%） ,P 〈0. 01. The BMI in patients with T allele （22.99 ± 3.24） of the INSR single nucleotide polymorphism was lower than that with C allele （25. 80 ±4. 01 ） ,P 〈0. 05. There were two gene types （C and CT） at the 39 site from the terminal exon 2 of the resistin gene. The C allele frequency of the PCOS group was 0.96（72/75）, CT cannula cusp frequency was 0. 04（ 3/75 ）. The C allele frequency of the control group was 0. 95 （63/66）, CT cannula cusp frequency 0. 05 （ 3/66）, the difference was not significant （ P 〉 0.05）. Conclusions The gene single nucleotide polymorphism of INSR may contribute to the occurrence and development of PCOS. Insulin receptor gene is one of the susceptibility genes in patients with PCOS, especially in the non-obese PCOS patients. Resistin intron 2 gene has polymorphism on the 39 site from the terminal exon 2. Resistin introns 2 gene pelymorphism is not associated with polycystic ovary syndrome.