Association of DRB1*04-DQB1*0301 haplotype and lack of association of two polymorphic sites at CTLA-4 gene with hashimoto's thyroiditis in an Italianpopulation
A. Petrone et al., Association of DRB1*04-DQB1*0301 haplotype and lack of association of two polymorphic sites at CTLA-4 gene with hashimoto's thyroiditis in an Italianpopulation, THYROID, 11(2), 2001, pp. 171-175
Hashimoto's thyroiditis (HT) is an autoimmune disease resulting from a comp
lex interaction between genetic and environmental factors. The genetic loci
conferring susceptibility need to be still defined. The aim of the present
study was to determine whether Cytotoxic T-Lymphocyte-Associated Antigen-4
(CTLA-4), HLA DRB1, and DQB1 genes were associated to HT in an Italian pop
ulation. We evaluated the allele distribution of the following loci: CTLA-4
exon 1 A49G dimorphism, which resulted in an amino acidic exchange (Tnr/Al
a) in the leader peptide, CTLA-4 3' microsatellite, HLA DRB1 and DQB1 in 12
6 patients with HT and in 301 control subjects from an Italian population (
Lazio region). CTLA-4 exon 1 A49G dimorphism was typed by Polymerase Chain
Reaction and Restriction Fragment Length Polymorphism (PCR-RFLP); CTLA-4 3'
microsatellite alleles were defined using a fluorescence-based method. HLA
DRB1 and DQB1 alleles were typed using a SSO reverse line blot method and
a probeless procedure based on allele group-specific amplification followed
by DNA heteroduplex analysis, respectively. Data were initially analyzed b
y chi (2) test or Fisher's exact test. Multiple logistic regression analysi
s was then applied on factors with significant crude odds ratios and on CTL
A-4 exon 1 A49G dimorphism to investigate their independent effects. The tw
o polymorphic sites at CTLA-4 gene did not increase the risk for HT. The di
stribution of HLA DRB1 and DQB1 alleles did not show any significant differ
ence between patients and controls, however, the DRB1*04-DQB1*0301 haplotyp
e was significantly increased in patients. Other factors that increase the
risk of disease were gender and age. Females showed approximately 18 times
more risk than males; subjects older than 50 years had an odds ratio of 6.6
. These data suggest that these two polymorphic sites at CTLA-4 do not play
a major role in the susceptibility of the disease in an Italian population
while female gender, age over 50 years, HLA DRB1*04-DQB1*0301 haplotype in
crease the risk of developing HT.