title: Association analysis of GWAS and candidate gene loci in a Pakistani population with psoriasis.
abstract: Psoriasis is a common inflammatory and hyper proliferative condition of the skin and a serious chronic systemic autoimmune disease. We undertook an association study to investigate the genetic etiology of psoriasis in a Pakistani population by genotyping single-nucleotide polymorphisms (SNPs) previously reported to be associated in genome-wide association (GWAS) or in candidate gene studies of psoriasis. Fifty seven single-nucleotide polymorphisms (SNPs) from 42 loci were genotyped in 533 psoriasis patients and 373 controls. Our results showed genome wide significant association of the MHC region (rs1265181 being the most significant from five SNPs used with overall OR=3.38; p=2.97E-18), as well as nominally significant associations at ten other loci (p<0.05) in the Pakistani population (LCE3B, REL, IL13/IL4, TNIP1, IL12B, TRAF3IP2, ZC3H12C, NOS2 and RNF114 from GWAS and PRR9 from a previous candidate gene study). Overall, only nine SNPs out of the 42 GWAS loci, displayed an odds ratio in the opposite allelic direction and only three did not reach similar odds ratio within 95% confidence interval as previously reported (SLC45A1/TNFRSF9, ELMO1 and IL28RA). This indicates similar genetic risk factors and molecular mechanisms behind disease in Pakistani psoriasis patients as in other populations. In addition, we show that the MHC and TNIP1 regions are significantly different in patients with psoriasis onset before the age of 40 (type I) compared to after 40 years of age (type II). MHC being associated mainly with type I while TNIP1 with type II patients.
authors.affiliation: Institute of Biomedical and Genetic Engineering, G-9/1, Islamabad, Pakistan; Department of Biochemistry, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Saeeda
authors.initials: S
authors.lastname: Munir
authors.affiliation: Skin and Laser Clinic, Peshawar Road, Rawalpindi, Pakistan.
authors.forename: Simeen
authors.initials: S
authors.lastname: ber Rahman
authors.affiliation: Institute of Biomedical and Genetic Engineering, G-9/1, Islamabad, Pakistan.
authors.forename: Sadia
authors.initials: S
authors.lastname: Rehman
authors.affiliation: Institute of Biomedical and Genetic Engineering, G-9/1, Islamabad, Pakistan.
authors.forename: Nusrat
authors.initials: N
authors.lastname: Saba
authors.affiliation: Department of Biochemistry, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Wasim
authors.initials: W
authors.lastname: Ahmad
authors.affiliation: Department of Mathematical Sciences, Chalmers University of Technology, Gothenburg, Sweden.
authors.forename: Staffan
authors.initials: S
authors.lastname: Nilsson
authors.affiliation: Institute of Biomedical and Genetic Engineering, G-9/1, Islamabad, Pakistan.
authors.forename: Kehkashan
authors.initials: K
authors.lastname: Mazhar
authors.affiliation: Department of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden. Electronic address: asa.torinsson.naluai@gu.se.
authors.forename: Åsa Torinsson
authors.initials: ÅT
authors.lastname: Naluai
mesh_terms: D000328:Adult; D005260:Female; D056426:Genetic Loci / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D010154:Pakistan; D020641:Polymorphism, Single Nucleotide; D011565:Psoriasis / Q000235:genetics*
keywords: Autoimmunity; Genetic risk factors; HLA; Molecular mechanisms; Psoriasis; Systemic immunity