title: ICAM1 K469E and E-selectin S128R polymorphisms could predispose to increased autoantibody production and TSH suppression in Graves' disease.
abstract: The etiopathogenesis of Graves' disease (GD) has not been clearly elucidated although the role of chronical inflammation and endothelial dysfunction has been established. Adhesion molecules such as intercellular adhesion molecule 1 (ICAM1), vascular cell adhesion molecule 1 (VCAM1), and E-selectin are secreted from vascular endothelium and promote accumulation of leukocytes in damaged endothelial areas. This study examined the possible association of ICAM1 (G241R and K469E), VCAM1 (T-1591C and T-833C), and E-selectin (S128R) single nucleotide polymorphisms (SNPs) with the occurrence of GD. ICAM1 (G241R and K469E), VCAM1 (T-1591C and T-833C), and E-selectin (S128R) SNPs in DNA from peripheral blood leukocytes of 171 patients with GD and 259 healthy controls were investigated by real-time PCR combined with melting curve analysis using fluorescence-labeled hybridization probes. We did not find significant differences in the distributions of studied polymorphisms, nor in the haplotype frequencies between patients with GD and healthy control. However, the anti-TPO levels in E-selectin 128R allele carrying subjects (SR + RR) were higher than S128S genotype (p < 0.05). In addition, the decline of TSH levels was more prominent in ICAM1 469 E carrying subjects (KE + EE) in comparison with wild homozygotes (p < 0.05). Although there is not association between ICAM1 (G241R and K469E), VCAM1 (T-1591C and T-833C), and E-selectin (S128R) SNPs and susceptibility to GD, higher anti-TPO in E-selectin 128 SR + RR, and lower TSH in ICAM1 469 KE + EE subjects suspect that these genotypes are prone to increased antithyroid autoantibody production with more accentuated TSH suppression in GD. Further studies with a larger cohort, analyzing other polymorphisms in ICAM, VCAM1 and E-selectin genes are necessary to support our observations.
authors.affiliation: Department of Biochemistry, Istanbul Faculty of Medicine, Istanbul University, Çapa, 34093, Istanbul, Turkey.
authors.forename: Müge
authors.initials: M
authors.lastname: Kanmaz-Özer
authors.forename: Semra
authors.initials: S
authors.lastname: Doğru-Abbasoğlu
authors.forename: Pervin
authors.initials: P
authors.lastname: Vural
authors.forename: Ayşenur
authors.initials: A
authors.lastname: Özderya
authors.forename: Berrin
authors.initials: B
authors.lastname: Karadağ
authors.forename: Müjdat
authors.initials: M
authors.lastname: Uysal
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D001323:Autoantibodies / Q000276:immunology*; D016022:Case-Control Studies; D019040:E-Selectin / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006111:Graves Disease / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology*; D006239:Haplotypes; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D013972:Thyrotropin / Q000276:immunology*; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D019040:E-Selectin; D018799:Intercellular Adhesion Molecule-1; D013972:Thyrotropin