Genome-Wide Association Study in an Amerindian Ancestry Population Reveals Novel Systemic Lupus Erythematosus Risk Loci and the Role of European Admixture.
We also found that the homozygous risk genotype of rs1059702 was associated with lower mRNA levels of MECP2, but not IRAK1, in SLE patients (p=0.0012) and healthy controls (p=0.0064).
Recently, an IRAK1 haplotype that contains the 196Phe functional variant (rs1059702), located on Xq28, was found to confer susceptibility to systemic lupus erythematosus (SLE).
MiRNA-146a rs2910164 and IRAK1 rs3027898 polymorphisms were a risk factor for predisposition to RA in codominant and dominant tested inheritance models, while, the miRNA-499 rs3746444 and PADI4 rs1748033 polymorphisms were a risk factor in codominant and recessive one.
The aim of the present study was to reveal if there is any association of miRNA-146a variant rs2910164 and the two interleukin (IL) 1 receptor associated kinase (IRAK1, a target gene of mir-146a) polymorphisms rs3027898 and rs1059703 with RA predisposition.
Among eight SSc-associated susceptibility polymorphisms which were applied for meta-analysis, IRF5 rs2004640 polymorphism (OR 1.12; 95% CI 1.02-1.22, P = 1.39 × 10<sup>-2</sup>), STAT4 rs7574865 polymorphism (OR 1.25; 95% CI 1.07-1.47, P = 5.3 × 10<sup>-3</sup>), IRAK1 rs1059702 polymorphism (OR 1.20; 95% CI 1.05-1.37, P = 0.007), and CTGF G-945C polymorphism (OR 1.42; 95% CI 1.18-1.71, P = 0.002) are associated with PF status in SSc, while TNFAIP3 rs5029939, CD226 rs763361, CD247 rs2056626, and IRF5 rs10488631 polymorphisms are not.
IRAK1 rs1059702 and MECP2 rs17435 were associated specifically with diffuse cutaneous SSc (PFDR=4.12×10(-3), OR=1.27, 95% CI 1.09 to 1.47, and PFDR=5.26×10(-4), OR=1.30, 95% CI 1.14 to 1.48, respectively), but conditional logistic regression analysis showed that the association of IRAK1 rs1059702 with this subtype was explained by that of MECP2 rs17435.
In both the discovery and replication sets, the rs1059702 TT genotype was found to be associated with specific SSc subsets, highlighting a potential contribution to disease severity.
Since interleukin-1 receptor-associated kinase (IRAK-1)/nuclear factor-kappa B (NF-kappa B) pathway plays an essential role in the pathogenesis of autoimmune diseases, the aim of the present study was to explore the role of polymorphisms in three genes, named IRAK1 (rs3027898), NFKBIA (rs696) and NFKB1 (-94ATTG insertion/deletion variant, - rs28362491), in PV susceptibility.
Among eight SSc-associated susceptibility polymorphisms which were applied for meta-analysis, IRF5 rs2004640 polymorphism (OR 1.12; 95% CI 1.02-1.22, P = 1.39 × 10<sup>-2</sup>), STAT4 rs7574865 polymorphism (OR 1.25; 95% CI 1.07-1.47, P = 5.3 × 10<sup>-3</sup>), IRAK1 rs1059702 polymorphism (OR 1.20; 95% CI 1.05-1.37, P = 0.007), and CTGF G-945C polymorphism (OR 1.42; 95% CI 1.18-1.71, P = 0.002) are associated with PF status in SSc, while TNFAIP3 rs5029939, CD226 rs763361, CD247 rs2056626, and IRF5 rs10488631 polymorphisms are not.
The rs13397 G and rs1059703 T major alleles were significantly increased in RA patients (<i>n</i> = 408) compared with age-matched controls (<i>n</i> = 471) in both Tunisian and French women.
Overall, the results showed that there were significant associations with ADs risk in three genetic models for rs3027898 and in four genetic models for rs1059702, but in neither model for rs1059703.
On the other hand, IRAK1 rs1059702 was consistently associated with presence of pulmonary fibrosis (PF), because statistical significance was observed when comparing SSc patients PF+ versus controls (PFDR=0.039, OR=1.30, 95% CI 1.07 to 1.58) and SSc patients PF+ versus SSc patients PF- (p=0.025, OR=1.26, 95% CI 1.03 to 1.55).
The aim of the present study was to reveal if there is any association of miRNA-146a variant rs2910164 and the two interleukin (IL) 1 receptor associated kinase (IRAK1, a target gene of mir-146a) polymorphisms rs3027898 and rs1059703 with RA predisposition.
Genotyping for miRNA-146a (rs2910164) and its target gene IRAK1 (rs3027898) was performed using real-time polymerase chain reaction (RT-PCR) in 80 patients with SLE and 70 patients with MS, as well as 120 healthy control individuals.
SIPD patients showed significant association between: leukocytosis > 15,000/mmc and rs1059702-nonTT (IRAK1; P = 0.0460), pleuropneumonia and rs1624395-G (IRAKM; P = 0.0147), and rs1370128-C (IRAKM; P = 0.0055), sequelae, and rs4251513-nonGG (IRAK4; P = 0.0055), death and rs6853-nonAA (P = 0.0054) and rs6853-G (P = 0.0065; MyD88).