尾加压素Ⅱ基因多态性与多囊卵巢综合征相关性的研究

Association of genetic variants in urotensin II gene with polycystic ovary syndrome

目的探讨尾加压素Ⅱ（UTS2）基因多态性与多囊卵巢综合征（PCOS）发病的关系。方法用熔解温度不同的基因分型法，检测PCOS患者101例（PCOS组）及其父母202名和105名健康妇女（对照组）UTS2基因rs228648、rs2890565位点单核苷酸多态性（SNP），并检测基础状态下FSH、LH、睾酮、空腹血糖、空腹胰岛素水平。结果PCOS组的UTS2基因rs228648A／G多态性位点与对照组比较，基因型与等位基因频率均无明显差异，两组的SNPrs2890565基因型频率差异有统计学意义（P〈0．05），PCOS组A等位基因频率明显高于对照组（P〈0．05）。传递不平衡检验（TDT）显示，SNPrs228648A／G在杂合子父母的2个不同等位基因无优势传递（P〉0．05），而rs2890565A／G在杂合子父母A等位基因优势传递（P〈0．05）。PCOS组UTS2基因SNPrs228648GG基因型较携带A等位基因的PCOS患者稳态模型评估的胰岛素抵抗指数（HOMA—IR）明显增高（P〈0．05）。SNPrs2890565AA和AG基因型空腹血糖、空腹胰岛素较GG基因型明显增高，AA基因型HOMA—IR较GG基因型明显增高（P〈0．05）。结论UTS2基因SNPrs228648A／G多态性与PCOS无相关性，但与胰岛素抵抗存在关联。UTS2基因SNPrs2890565可能在PCOS的遗传易感性中起一定作用，A等位基因可能与PCOS的发生有关。

Objective To investigate the correlation of single nueleotide polymorphisms （SNP） of rs228648 and rs2890565 in urotensin 11 （UTS2）gene with polycystie ovary syndrome（PCOS）. Methods The genotypes of two SNPs in UTS2 gene were determined through polymerase chain reaction Tm-shift genotyping method. 101 Chinese Han families trios in Shandong Province consisting of fathers, mothers, and affected daughters with PCOS and 105 healthy women were recruited. The physiological and biochemical parameters including serum follicular stimulating hormone（FSH） ,luteinizing hormone（LH）, testosterone,fasting plasma glucose, and insulin were also measured. Results The distributions of three genotypes and two alleles of SNP rs228648 in UTS2 gene were similar between PCOS group and control group. The distributions of genotypes of SNP rs2890565 in UTS2 gene differed significantly between PCOS group and control group （P 〈 0. 05 ）. The frequency of A allele of SNP rs2890565 in UTS2 gene was significantly higher in PCOS group than that in control group（ P〈0.05 ）. Transmission disequilibrium test（TDT）did not show significantly biased transmission of two different alleles from parents to affected daughters at rs228648 locus （P〉0.05）, but showed an excess transmission of A allele from heterozygous parents to affected offspring at rs2890565 locus（P〈0.05）. The carriers with GG genotype of SNP rs22864g had significantly higher HOMA-IR compared to those with AA and AG genotypes. The carriers with AA or AG genotype of SNP rs2890565 had significantly higher fasting plasma glucose and fasting insulin compared to those with GG genotypes. HOMA-IR in cases with AA genotype was significantly higher than that with GG genotype. Conclusions There is no association of SNP rs228648 with PCOS, but exists association with insulin resistance. The genetic polymorphism of UTS2 gene rs2890565 may be associated with PCOS, and the higher frequency of A allele is likely to contribute to PCOS.