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Rheumatology (Oxford). 2019 Feb 1;58(2):289-298. doi: 10.1093/rheumatology/key281.

Analysis of the genetic component of systemic sclerosis in Iranian and Turkish populations through a genome-wide association study.

Author information

1
Cell Biology and Immunology Department, Institute of Parasitology and Biomedicine López-Neyra, Consejo Superior de Investigaciones Científicas, Granada, Spain.
2
Department of Rheumatology, Istanbul Bilim University, Istanbul, Turkey.
3
Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran.
4
Department of Rheumatology, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
5
Division of Rheumatology, Marmara University, Istanbul, Turkey.
6
Department of Physiology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
7
Division of Rheumatology, Department of Internal Medicine, Ann Arbor MI, USA.
8
Department of Computational Medicine and Bioinformatics, The Center for Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor MI, USA.
9
Institute of Health and Biomedical Innovation, Queensland University of Technology, Translational Research Institute, Princess Alexandra Hospital, Queensland, Australia.

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.

PMID:
30247649
DOI:
10.1093/rheumatology/key281
[Indexed for MEDLINE]

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