Analysis of the genetic component of systemic sclerosis in Iranian and Turkish populations through a genome-wide association study. (21st September 2018)

• Record Type: Journal Article
• Authors: González-Serna, David; López-Isac, Elena; Yilmaz, Neslihan; Gharibdoost, Farhad; Jamshidi, Ahmadreza; Kavosi, Hoda; Poursani, Shiva; Farsad, Faraneh; Direskeneli, Haner; Saruhan-Direskeneli, Guhrer; Vargas, Sofia; Sawalha, Amr H; Brown, Matthew A; Yavuz, Sule; Mahmoudi, Mahdi; Martin, Javier
• Is Part Of: Rheumatology. Volume 58:Number 2(2019)
• Page Start: 289
• Page End: 298
• Publication Date: 2018-09-21
• Subjects: SSc -- GWAS -- Iranian and Turkish populations -- risk loci; Rheumatism -- Periodicals; Rheumatology -- Periodicals; 616.723005
• DOI: 10.1093/rheumatology/key281
• Languages: English
• ISSNs: 1462-0324

Abstract

Abstract: Objectives: SSc is an autoimmune disease characterized by alteration of the immune response, vasculopathy and fibrosis. Most genetic studies on SSc have been performed in European-ancestry populations. The aim of this study was to analyse the genetic component of SSc in Middle Eastern patients from Iran and Turkey through a genome-wide association study. Methods: This study analysed data from a total of 834 patients diagnosed with SSc and 1455 healthy controls from Iran and Turkey. DNA was genotyped using high-throughput genotyping platforms. The data generated were imputed using the Michigan Imputation Server, and the Haplotype Reference Consortium as a reference panel. A meta-analysis combining both case–control sets was conducted by the inverse variance method. Results: The highest peak of association belonged to the HLA region in both the Iranian and Turkish populations. Strong and independent associations between the classical alleles HLA-DRB1*11: 04 [ P = 2.10 × 10 −24, odds ratio (OR) = 3.14] and DPB1*13: 01 ( P = 5.37 × 10 −14, OR = 5.75) and SSc were observed in the Iranian population. HLA-DRB1*11: 04 ( P = 4.90 × 10 −11, OR = 2.93) was the only independent signal associated in the Turkish cohort. An omnibus test yielded HLA-DRB1 58 and HLA-DPB1 76 as relevant amino acid positions for this disease. Concerning the meta-analysis, we also identified two associations close to the genome-wide significance level outside the HLA region, corresponding to IRF5-TNPO3 rs17424921-C ( P = 1.34 × 10 −7, OR = 1.68) and NFKB1 rs4648133-C ( P = 3.11 × 10 −7, OR = 1.47). Conclusion: We identified significant associations in the HLA region and suggestive associations in IRF5-TNPO3 and NFKB1 loci in Iranian and Turkish patients affected by SSc through a genome-wide association study and an extensive HLA analysis.