The CAG Repeat Polymorphism At Androgen Receptor Gene Exon 1 Is Associated With Predisposition To Uterine Leiomyoma

Uterine leiomyoma is one of the most frequent neoplasms, occurring in 25% to 77% of adult women. While most of the cases are benign, its behavior in patients remains unpredicatable. Some histologically benign tumors may show aggressiveness or even metastasis to distant organs. These cases carry two or more nodules, falling into the category of multiple uterine leiomyomas. To disclose the related factors of genetic sensitivity among multiple cases may help to find the people who are sensitive to it, and may help for the diagnosis and therapy for the disease.Random inactivation of one X-chromosome in somatic cells offers a probability for the clonality analysis. The inactivation pattern can also be used as a parameter to describle the individual genetic sensitivity in cases of the same desease. Recently, we have established a clonality assay based on X-chromosome polymorphism at the phosphoglycerate kinase (PGK) locus, our data indicating that some multiple leiomyomas may be unicentric. The relationshipamong nodules of mutiple leiomyomas seems not simple as before which includes multi-centric, unicentric and both of them. Furthermore we established the non-isotopic clonality assay based on inactivation patterns of the polymorphic X-chromosomes at androgen receptor (AR) locus and approve our previous finding. In this study, the following tests were performed: 1) 10 cases samples were selected as control to estimate the MW and N values of female samples by sequensing the PCR products at AR allele which has different length. 2) CAG repeat length of 14 female samples were selected as cintrol. 3) The associations of short tandem repeat (STR) CAG among different nodules and different type in multiple cases were checked.This study show :1) Number of the CAG repeats in a reference group of the male sample ranged from 11 to 30, with their mean value being 21.4(median value 22.5); 2) Number of the CAG repeats in a reference group of the female sample ranged from 17 to 28, with their mean value being 21.3(median value 22).3) For leiomyoma with one, two or three and more than three nodules, the mean values were 21.2, 21.3 and 21.8(median value 21, 21, 22). The difference was statistically significant (P<0.05), indicating a predisposing role of the longer STR in the development of multiple uterine leiomyomas. Number of the CAG repeats in multiple leiomyomas of the unicentric and mixed types ranged from 16 to 25 and from 19 to 26.The mean value were 20.4, being significantly smaller than that in the multicentric cases (22.1), further revealing that the unicentric and multicentric uterine leiomyomas might corelated to individual genetic sensitivity.In the study, we have approved that the CAG STR polymorphism at the AR gene exon 1 plays some role in the development or progression of multiple uterine leiomyomas. The individuals with the longer alleles may be more predisposed to the neoplasm and the multicentric type of multiple leiomyomas. We have found that the STR(CAG) at AR gene locus may play a role in the development of mutiple uterine leiomyomas.The case who has the longer CAG repeat are apt to have this kind of tumor and to develop multi-centric type of desease.