Fas ligand gene polymorphisms are not associated with Hashimoto's thyroiditis and Graves' disease.
Hashimoto's thyroiditis and Graves' disease represent the two most common autoimmune thyroid disorders. Whereas in Hashimoto's thyroiditis FasL expression causes thyrocytes to undergo apoptosis, additional anti-apoptotic molecules appear to protect these cells in Graves' disease. Mutations of the FasL gene were observed in systemic lupus erythematosus. Given its functional relevance for the pathogenesis of thyroid autoimmunity we wondered whether variants of the FasL gene play a role in Hashimoto's thyroiditis and Graves' disease. We genotyped families with at least one offspring affected by Hashimoto's thyroiditis (n = 86) and Graves' disease (n = 90) for two FasL gene polymorphisms (C -843 T in the promoter, A IVS2nt-124 G in intron 2). Extended transmission disequilibrium (ETDT) and chi(2) testing were performed. Neither polymorphism alone nor the promoter/intron 2 haplotypes (p = 0.91) were associated with Hashimoto's thyroiditis. No association with Graves' disease was observed for the promoter polymorphism (p = 0.91) and the intron 2 "A" allele (57.1%; p = 0.36) or the promoter/intron 2 haplotypes (p = 0.31). Moreover, intron 2 genotyping revealed no difference between an additional 251 patients with Graves' disease and 197 healthy controls (p = 0.37). Italian and German families did not differ for the studied polymorphisms. In conclusion, our data do not suggest common genetic FasL variants to significantly contribute to the pathogenesis of either Hashimoto's thyroiditis or Graves' disease.
Stuck
Bettina J
BJ
Department of Internal Medicine I, University Hospital Frankfurt am Main, Germany.
Pani
Michael A
MA
Besrour
Foued
F
Segni
Maria
M
Krause
Maren
M
Usadel
Klaus-H
KH
Badenhoop
Klaus
K
D001327:Autoimmune Diseases / Q000453:epidemiology / Q000235:genetics*; D016009:Chi-Square Distribution; D053222:Fas Ligand Protein; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006111:Graves Disease / Q000453:epidemiology / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007438:Introns / Q000235:genetics; D007558:Italy / Q000453:epidemiology; D015810:Linkage Disequilibrium; D008562:Membrane Glycoproteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D013967:Thyroiditis, Autoimmune / Q000453:epidemiology / Q000235:genetics*; D044465:White People / Q000235:genetics
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins