title: Association of CCR5, TLR2, TLR4 and MBL genetic variations with genital tract infections and tubal factor infertility.
abstract: Upper genital tract infections can inflict inadequate immune response and cause Fallopian tube damage and concomitant female infertility. However, the exact role of host genetic variation in the development of tubal factor infertility remains unclear. We selected nine genetic variations in four genes involved in immune response modulation (CCR5, TLR2, TLR4 and MBL2) and assessed their association with tubal factor infertility by comparing genotype frequencies among 163 women with tubal factor infertility and 400 control individuals. The CCR5, TLR2 and TLR4 genotypes were not associated with tubal factor infertility, although the TLR4 Asp299Gly and Thr399Ile heterozygosity was associated with a decreased incidence of pathogens associated with genital tract infections in tubal factor infertility patients. In contrast, MBL2 low-producing genotypes were associated with an increased incidence of such pathogens. In addition, hyper-producing MBL2 genotype HYA/HYA and low-producing MBL2 genotypes were associated with susceptibility to tubal factor infertility, while a protective effect was associated with the high-producing MBL2 genotype HYA/LYA. Overall, these data suggest that polymorphisms in TLR4 and MBL2 play a role in receptiveness to pathogens causing genital tract infections, while MBL2 genotypes contribute to susceptibility to tubal factor infertility.
authors.affiliation: Department of Obstetrics and Gynecology, University of Tartu, L. Puusepa 8, 51014 Tartu, Estonia. triin.laisk@ut.ee
authors.forename: Triin
authors.initials: T
authors.lastname: Laisk
authors.forename: Maire
authors.initials: M
authors.lastname: Peters
authors.forename: Merli
authors.initials: M
authors.lastname: Saare
authors.forename: Kadri
authors.initials: K
authors.lastname: Haller-Kikkatalo
authors.forename: Helle
authors.initials: H
authors.lastname: Karro
authors.forename: Andres
authors.initials: A
authors.lastname: Salumets
mesh_terms: D002690:Chlamydia Infections / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D002692:Chlamydia trachomatis; D004198:Disease Susceptibility; D005187:Fallopian Tubes / Q000382:microbiology / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005831:Genital Diseases, Female / Q000235:genetics* / Q000382:microbiology; D005838:Genotype; D006801:Humans; D007247:Infertility, Female / Q000235:genetics* / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D037601:Mannose-Binding Lectin / Q000235:genetics* / Q000276:immunology; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D019713:Receptors, CCR5 / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000235:genetics* / Q000276:immunology
chemical_list: C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin; D019713:Receptors, CCR5; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4