Association of interleukin 1beta gene (+3953) polymorphism and severity of endometriosis in Turkish women

Abstract

Endometriosis is regarded as a complex trait, in which genetic and environmental factors contribute to the disease phenotype. We investigated whether the interleukin (IL) 1beta (+3953) polymorphism is associated with the severity of endometriosis. Diagnosis of endometriosis was made on the basis of laparoscopic findings. Stage of endometriosis was determined according to the Revised American Fertility Society classification. 118 women were enrolled in the study. 78 women did not have endometriosis, 6 women had stage I, 3 had stage II, 13 had stage III and 18 had stage IV endometriosis. Polymerase Chain Reaction (PCR), Restriction Fragment Length Polymorphism (RFLP), and agarose gel electrophoresis techniques were used to determine the IL 1beta (+3953) genotype. Frequencies of the IL-1beta (+3953) genotypes in the control group were: CC, 0.397; TT, 0.115; CT, 0.487. Frequencies of the IL-1beta (+3953) genotypes in cases were: CC, 0.375; TT, 0.225; CT, 0.400. We found a 2.22 fold increase in TT genotype in the endometriosis group. However, the difference was not statistically significant (P > 0.05). We also observed an increase in the frequency of IL-1beta (+3953) T allele in the endometriosis group. However, the difference was not statistically significant. We also investigated the association between IL-1beta (+3953) polymorphism and the severity of endometriosis. The frequencies of CC+CT genotypes in stage I, III and IV endometriosis patients were 83.3, 84/6 and 72.2%, respectively; and TT genotypes were 16.7, 15.4 and 27.8%, respectively. We observed a statistically insignificant increase in TT genotype in stage IV endometriosis (P > 0.05). We suggest that IL-1beta (+3953) polymorphism is not associated with endometriosis in Turkish women.

Defining the genetic profile of endometriosis (Review)

“…Non-relation has been underlined between endometriosis and the IL-1β −511 promoter, IL-1β exon 5 and IL-1 receptor antagonist genetic variations, since proportions of various polymorphisms did not seem to differ significantly between a group of patients (n=120) and healthy controls (n=103) in a previous study (101). Notably, the association between IL-1β (+3953) polymorphism endometriosis in a Turkish population was assessed as negative, since statistically insignificant proved to be the increased frequency of the respective genotypes (102). On the other hand, additional evidence exists for a positive correlation between the IL1A locus and endometriosis (103).…”

Polymorphisms of TNF-alpha (− 308), IL-1beta (+ 3954) and IL1-Ra (VNTR) are associated to severe stage of endometriosis in Mexican women: a case control study

“…All five studies (Turkey, Taiwan, China, Austria, Mexico) that have investigated the relationship between the C+3954T SNP and endometriosis found a negative association. The allele frequencies identified range from 1 to 43% in women with endometriosis [49][50][51][52]. Attar [51], like us, identified an increased frequency in endometriosis stage IV (27%, p = 0.056), which could be related to an increased synthesis of IL-1β by peritoneal immune and non-immune cells that can induce the expression of different molecules involved in the immunological dysfunctions contributing to the establishment and progression of the disease.…”

Factores inmunogen�ticos asociados al desarrollo de endometriosis

“…El SNP +3953 T/C fue analizado en mujeres europeas con endometriosis, en las cuales no se encontró asociación entre este polimorfismo con endometriosis ni con el aumento de la citocina IL-1β 71 , mientras que Attar, et al 72 encontraron que la frecuencia genotípica TT y la frecuencia alélica T fue mayor en pacientes turcas con endometriosis y que el genotipo TT estuvo asociado a estados avanzados de endometriosis. El alelo T tiene resultados controvertidos respeto a la producción de IL-1β, ya que Santtila, et al 73 reportaron una producción menor, mientras que Pociot, et al 74 observaron lo contrario, así como el genotipo TT se observó asociado a un aumento en la producción de dicha citocina 75 .…”