Maria Ammendola

The association of PTPN22 polymorphism with endometriosis: effect of genetic and clinical factors

OBJECTIVE To investigate the possible effect of clinical and genetic variables on the association between PTPN22 and endometriosis. METHODS PTPN22, ACP₁ and p53 codon 72 genetic polymorphisms and duration of previous pharmacological treatment were studied. The study sample consisted of 132 women hospitalized for endometriosis diagnosed by laparoscopic intervention and histologically confirmed: 359 healthy blood donors were studied as controls. PTPN22, ACP1 and p53 codon 72 genotypes were determined by DNA analysis. Discriminant statistical analysis, logistic regression analysis, chi square of independence, power test and linear correlation were performed using SPSS programs. RESULTS A significant increase of PTPN22 *T allele in endometriosis is observed in women carrying ACP1*C allele, in women carrying p53 codon 72 *Pro allele and in women with prolonged pharmacological treatment. CONCLUSIONS PTPN22 may not be a primary factor in the etiology of endometriosis but may cooperate with clinical and genetic factors influencing susceptibility and clinical course of disease. These new observations point to a multifactorial origin of endometriosis and help to explain the reported differences between human populations concerning the association between PTPN22 and endometriosis.

ACP1 is associated with allergy

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Acid phosphatase locus 1 genetic polymorphism, endometriosis, and allergy

Recent studies suggest that acid phosphatase locus 1 (ACP1) could be involved in T-cell antigen receptor signaling and in immune disorders. The present study shows that the ACP1( *)C allele, which is associated with elevated enzymatic activity, is significantly more common in women with endometriosis than in healthy women, but is less common in allergic than in nonallergic subjects. These findings suggest that carriers of high activity ACP1 genotypes are more susceptible to endometriosis but less susceptible to allergic manifestations than carriers of other ACP1 genotypes.

Is there an association between uterine leiomyomas and acid phosphatase locus 1 polymorphism

OBJECTIVE Platelet derived growth factor (PDGF) is involved in the development of leiomyomas. The low-molecular-weight phosphoprotein-tyrosine-phosphatase (LMWPTP), controlled by the highly polymorphic acid phosphatase locus 1 (ACP1), is able to dephosphorylate the PDGF receptor. Therefore, we searched for a possible association between ACP1 and leiomyomas. STUDY DESIGN We studied 172 women hospitalized for symptomatic leiomyomas requiring surgical intervention and 164 healthy women without clinical evidence of leiomyomas from the same white population. The chi(2) test of independence, Pearson correlation, analysis of variance, and post hoc test for difference between means were performed. RESULTS The distribution of ACP1 genotypes among patients does not differ significantly from that of healthy women. However, leiomyoma size was negatively correlated with ACP1 F isoform concentrations. Leiomyoma size was smaller among carriers of the *B/*B genotype, which has the highest concentration of the F isoform, than among carriers of *A/*A, *C/*B, and *C/*C genotypes, which have the lowest concentration of the F isoform. CONCLUSION High ACP1 F isoform concentration, through dephosphorylation of the PDGF receptor, may negatively regulate cell proliferation and growth of leiomyomas.

Genetic variability within Adenosine Deaminase gene and uterine leiomyomas

OBJECTIVE The recent observation of an association of colon cancer with two polymorphic sites within the Adenosine Deaminase (ADA) gene suggests an involvement of these polymorphisms in the development of solid tumors. This prompted us to search for a similar association in uterine leiomyomas. STUDY DESIGN We have studied 181 women admitted to the hospital for leiomyomas requiring surgical intervention and 248 women of comparable age without clinical signs of leiomyomas. All women were from the White population of Rome and gave verbal consent to participate in the study. The genotypes of three polymorphic sites (ADA1, ADA2, ADA6) of ADA gene were determined by DNA analysis. RESULTS A higher proportion of ADA2*1/*1 genotype and of carriers of the ADA6*1 allele was observed in women with leiomyomas as compared to controls. This parallels the association found in colon cancer. CONCLUSIONS This pattern is identical to that previously observed in colon cancer making the possibility of mere sample chance artifact unlikely and supporting the hypothesis that genetic polymorphisms within the ADA gene could be involved in the susceptibility to solid tumors. Genetic variability within the ADA gene may influence adenosine concentration and in turn the immune response by lymphocytes in solid tumors. On the other hand ADA molecules acting as ecto-enzyme may be involved in the transduction of signals in the cell surface with important effects on tumor development.

PTPN22 and uterine leiomyomas

OBJECTIVE It has been suggested that the development of uterine leiomyomas is positively influenced by an immune system in a chronically inflammatory state and that a lower level of regulating T cell (Treg cells) would play a central role. Since it has been suggested that the W620 variant of protein tyrosine phosphatase non-receptor type 22 (PTPN22) decreases the number of Treg cells, we investigated a possible relationship between PTPN22 polymorphism and uterine leiomyomas. STUDY DESIGN We studied 203 white women from Rome who were hospitalized for symptomatic leiomyomas requiring surgical intervention. These women were considered in a previous paper regarding the relationship between ACP1 and dimension of leiomyomas. As controls we studied 355 healthy women from the same population with comparable age and without clinical evidence of leiomyomas. All women gave written informed consent to participate to the study. Chi square test of independence and T-test for difference between means were performed by SPSS package. RESULTS Considering the whole sample, a borderline association between PTPN22 and leiomyomas was observed: the *C/*T genotype is more frequent in cases than in controls. This association is marked and statistically significant in younger women only. The main diameter of tumor is significantly greater in *C/*T than in *C/*C women. This effect is present in younger women only. The *C/*T genotype also shows a higher tendency to intramural localization, but no effect of age is observed upon this association. CONCLUSIONS The data suggest a positive effect of *C/*T genotype on susceptibility to leiomyomas in younger women. In these women a *C/*T genotype favors the growth of leiomyomas.

The effect of ACP1, ADA6 and PTPN22 genetic polymorphisms on the association between p53 codon 72 polymorphism and endometriosis

PurposeAssociation between p53 codon 72 and endometriosis has been observed in populations of East Asia but not in those of European descent. Genetic polymorphisms could interact with p53 codon 72 influencing its association with endometriosis, thus explaining these differences among populations.Methods130 women hospitalized for endometriosis and a sample of 250 women without endometriosis have been studied. All women were from the White population of Rome. ACP1, PTPN22, ADA6 and p53 codon 72 genotypes were determined by DNA analysis. Statistical analysis was performed by SPSS package. Three-way contingency table analyses were performed by a log linear model according to Sokal and Rohlf.ResultsThere is an epistatic interaction among ADA6, p53 codon 72 and endometriosis resulting in a positive association between carriers of *Pro allele of p53 codon 72 and endometriosis in women carrying the ADA6 *1 allele. PTPN22 and ACP1 show an additive effect with p53 codon 72 concerning their effect on endometriosis. The strength of association between p53 codon 72 and endometriosis is positively correlated with the number of the three factors considered.ConclusionADA6, PTPN22 and ACP1 are involved in immune reactions: since endometriosis has an autoimmune component, a cooperative interaction among these genetic systems appears biological plausible. The present result could contribute to explain the differences observed among populations concerning the association between p53 codon 72 and endometriosis.