The T allele of rs10036748 in the TNIP1 gene is the minor protective allele for asthma but the minor or major risk allele for systemic lupus erythematosus and systemic sclerosis in non-Hispanic white or Chinese subjects, respectively.
The genetic signal of association with TNIP1 variants, together with tissular and cellular investigations, suggests that this pathway has a critical role in regulating autoimmunity and SSc pathogenesis.
We genotyped a polymorphism (G-945C) in the promoter of the connective-tissue growth factor (CTGF) gene in 1000 subjects in two groups: group 1, consisting of 200 patients with systemic sclerosis and 188 control subjects; and group 2, consisting of 300 patients with systemic sclerosis and 312 control subjects.
Connective tissue growth factor (CTGF) has been implicated in the cardiac and kidney complications of type 2 diabetes, and the CTGF-945 G/C polymorphism is associated with susceptibility to systemic sclerosis, a disease characterised by tissue fibrosis.
The increase in DRB1*1502-DRB5*0102 haplotype supported the hypothesis of Reveille, et al that uncharged polar amino acid residue at position 30 of HLA-DQB1 allele was important for a-Scl-70 positive PSS because close association of the haplotype with DQB1*0601 was well established in Japanese; listed as a hypothetical candidate of PSS susceptible DQB1 allele.
Antifibrillarin, although an infrequent nucleolar autoantibody, is a marker for severe SSc, especially in blacks and males, and is strongly associated with a unique HLA haplotype, as well as with combinations of certain HLA-DQB1 alleles.
To examine the role of HLA-DRB1 and HLA-DQB1 alleles in the susceptibility to systemic sclerosis (SSc) and its clinical expression in a Spanish population.
We assessed the possible association between 7 single-nucleotide polymorphisms (SNP) in the CTGF gene and scleroderma in a French population (registration number 2006/0182).
CTGF has been linked to transforming growth factor-beta (TGF-beta) pathways in fibroproliferative diseases and specific polymorphisms within the CTGF gene may predispose for fibrosis in systemic sclerosis.
Polymorphisms in exons 2-4 for HLA-A, -B, -C loci, exon 2 for HLA-DRB1 and exons 2,3 for HLA-DQB1 were analyzed for association with PSS at allele and haplotype levels.
The results do not confirm previous findings and suggest that the CTGF -945 promoter polymorphism does not play a major role in SSc susceptibility or clinical phenotype.
Although many studies have analyzed HLA allele frequencies in several ethnic groups in patients with scleroderma (SSc), none has been done in French Caucasian patients and none has evaluated which one of the common amino acid sequences, (67)FLEDR(71), shared by HLA-DRB susceptibility alleles, or (71)TRAELDT(77), shared by HLA-DQB1 susceptibility alleles in SSc, was the most important to develop the disease.
This study confirms the association between an SNP in the CTGF gene and susceptibility to SSc, especially in the presence of diffuse cutaneous SSc, interstitial lung disease and anti-topoisomerase I antibody.