title: Association analysis of interleukin gene polymorphisms in autoimmune thyroid diseases in the Tunisian population.
abstract: Autoimmune thyroid diseases (AITDs), including Graves' disease (GD) and autoimmune hypothyroidism (AH), are inherited as complex traits. Among the genes contributing to AITDs susceptibility are genes of the IL-1 family. IL-1 regulates T and B lymphocyte maturation, including the induction of several cytokines and cytokine receptors. Therefore, disturbances of this balance may not only play a role in inflammation but also in the pathogenesis of autoimmunity. In order to investigate genetic association of IL-1 gene polymorphisms with AITDs, we performed both a familial study in a large Tunisian pedigree with high prevalence of AITDs (64 patients and 176 controls), and a case-control study (131 GD unrelated patients and 225 healthy controls). PCR and PCR-RFLP methods were used to analyse respectively a VNTR in the IL-1RN gene and three SNPs in both IL-1B genes (-511 C/T and +3954 C/T) and IL-1A (-889 C/T). The family-based association study showed an association of the IL-1B+3954 C/T polymorphism (p=0.02) and two haplotypes IL-1RN*3/C/T/T and IL-1RN*1/C/T/T (p=0.009 and p=0.047 respectively) with AITDs. The case-control study is the first study revealing a significant association of the IL-1A-889 C/T polymorphism (chi2=10.23; p=0.0014) with susceptibility to GD. Our data suggest that the IL-1 gene cluster may harbour susceptibility genes for AITDs and GD pathogenesis in the Tunisian population.
authors.affiliation: Unité cibles diagnostiques et thérapeutiques en pathologies humaines, Centre de biotechnologie de Sfax, Tunisie.
authors.forename: Maha
authors.initials: M
authors.lastname: Kammoun-Krichen
authors.forename: Noura
authors.initials: N
authors.lastname: Bougacha-Elleuch
authors.forename: Kaouthar
authors.initials: K
authors.lastname: Makni
authors.forename: Maha
authors.initials: M
authors.lastname: Rebai
authors.forename: Sylvie
authors.initials: S
authors.lastname: Peraldi-Roux
authors.forename: Ahmed
authors.initials: A
authors.lastname: Rebai
authors.forename: Mouna
authors.initials: M
authors.lastname: Mnif
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abid
authors.forename: Joumaa
authors.initials: J
authors.lastname: Jouida
authors.forename: Hammadi
authors.initials: H
authors.lastname: Ayadi
mesh_terms: D000483:Alleles; D001327:Autoimmune Diseases / Q000235:genetics*; D016022:Case-Control Studies; D005192:Family Health; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D015233:Models, Statistical; D010375:Pedigree; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D013959:Thyroid Diseases / Q000235:genetics*; D014416:Tunisia
chemical_list: D007375:Interleukin-1