Analysis of MHC genes in a Tunisian isolate with autoimmune thyroid diseases: implication of TNF -308 gene polymorphism.
Autoimmune thyroid diseases (AITDs), which include Hashimoto thyroiditis (HT), Graves' disease (GD) and primary idiopathic myxoedema (PIM), are recognized as multifactorial diseases. In this study, we have examined single and haplotypic genetic variation across the major histocompatibility complex (MHC) in a Tunisian isolate with a high prevalence of AITDs (62 patients: 32 with GD, 9 with HT and 21 with PIM). Genotyping was performed for HLA class I and II alleles as well as polymorphisms within tumor necrosis factor (TNF), lymphotoxin alpha (TLalpha) and heat shock protein (HSP70-02 and HSP70-hom) genes. Our results showed association of HLA-A2-B50-TNF 2 haplotype with AITDs (p = 0.045). Linkage analysis using Simwalk2 program has shown significant result with TNF -308 gene polymorphism (p = 0.03). The FBAT has given evidence for genetic association with TNF -308 and HLA-DR gene polymorphisms. TNF 2 allele was associated with GD (p = 0.0011), whereas TNF 1, HLA-DR11 and DR12 (p = 0.0039, p = 0.00089 and p = 0.0056, respectively) were rather implicated in HT pathogenesis. Results found by TDT-STDT have confirmed the involvement of the TNF -308 gene polymorphism in AITD pathogenesis (p < 10(-9)).
Bougacha-Elleuch
Noura
N
Laboratoire de Génétique Moléculaire Humaine Faculté de Médecine, Avenue Majida Boulila, 3029 Sfax, Tunisia.
Rebai
Ahmed
A
Mnif
Mouna
M
Makni
Hafedh
H
Bellassouad
Mohamed
M
Jouida
Jomaa
J
Abid
Mohamed
M
Hammadi
A
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002874:Chromosome Mapping; D005260:Female; D006111:Graves Disease / Q000235:genetics / Q000276:immunology; D006801:Humans; D008285:Major Histocompatibility Complex; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D013967:Thyroiditis, Autoimmune / Q000235:genetics / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology*; D014416:Tunisia
D014409:Tumor Necrosis Factor-alpha