ANALYSIS OF ASSOCIATIONS OF POLYMORPHISMS IN THE GENES CODING FOR L4, IL10, IL13 WITH THE DEVELOPMENT OF ATOPIC BRONCHIAL ASTHMA AND ITS REMISSION
BULLETIN OF RUSSIAN STATE MEDICAL UNIVERSITY
Authors: Zhorina, Yu, V; Abramovskikh, O. S.; Ignatova, G. U.; Ploshchanskay, O. G.
Abstract
Bronchial asthma is a multifactorial disease underpinned by chronic inflammation. The atopic phenotype of BA implies the presence of similar molecular mechanisms of pathogenesis between the patients. The aim of this study was to analyze the associations between the development of atopic BA/its remission and the following polymorphisms of interleukin genes: IL4 (rs2243250; C-589T), IL10 (rs1800896; G-1082A; rs1800872; C-592A), and IL13 (rs20541; Arg130Gln). Using allele-specific polymerase chain reaction (PCR), we studied the listed SNPs in the mixed urban sample of patients with BA (n = 53) and the controls (n = 30) residing in South Ural. The analysis revealed that genotype AA of IL10 (rs1800872) occurred more frequently in the control group (23.3%) than in the patients with atopic BA (5.7%) (OR = 0.197; 95% CI [0.047-0.832]; p = 0.031). No differences in genotype frequencies were observed between the patients with atopic BA and the controls for other studied polymorphisms. Our study failed to demonstrate the association of the listed polymorphisms and BA remission.
Fine mapping of eight psoriasis susceptibility loci
EUROPEAN JOURNAL OF HUMAN GENETICS
Authors: Das, Sayantan; Stuart, Philip E.; Ding, Jun; Tejasvi, Trilokraj; Li, Yanming; Tsoi, Lam C.; Chandran, Vinod; Fischer, Judith; Helms, Cynthia; Duffin, Kristina Callis; Voorhees, John J.; Bowcock, Anne M.; Krueger, Gerald G.; Lathrop, G. Mark; Nair, Rajan P.; Rahman, Proton; Abecasis, Goncalo R.; Gladman, Dafna; Elder, James T.
Abstract
Previous studies have identified 41 independent genome-wide significant psoriasis susceptibility loci. After our first psoriasis genome-wide association study, we designed a custom genotyping array to fine-map eight genome-wide significant susceptibility loci known at that time (IL23R, IL13, IL12B, TNIP1, MHC, TNFAIP3, IL23A and RNF114) enabling genotyping of 2269 single-nucleotide polymorphisms (SNPs) in the eight loci for 2699 psoriasis cases and 2107 unaffected controls of European ancestry. We imputed these data using the latest 1000 Genome reference haplotypes, which included both indels and SNPs, to increase the marker density of the eight loci to 49 239 genetic variants. Using stepwise conditional association analysis, we identified nine independent signals distributed across six of the eight loci. In the major histocompatibility complex (MHC) region, we detected three independent signals at rs114255771 (P = 2.94 x 10(-74)), rs6924962 (P = 3.21 x 10(-19)) and rs892666 (P = 1.11 x 10(-10)). Near IL12B we detected two independent signals at rs62377586 (P = 7.42 x 10(-16)) and rs918518 (P = 3.22 x 10(-11)). Only one signal was observed in each of the TNIP1 (rs17728338; P = 4.15 x 10(-13)), IL13 (rs1295685; P = 1.65 x 10(-7)), IL23A (rs61937678; P = 1.82 x 10(-7)) and TNFAIP3 (rs642627; P = 5.90 x 10(-7)) regions. We also imputed variants for eight HLA genes and found that SNP rs114255771 yielded a more significant association than any HLA allele or amino-acid residue. Further analysis revealed that the HLA-C*06-B*57 haplotype tagged by this SNP had a significantly higher odds ratio than other HLA-C*06-bearing haplotypes. The results demonstrate allelic heterogeneity at IL12B and identify a high-risk MHC class I haplotype, consistent with the existence of multiple psoriasis effectors in the MHC.