Possible single-nucleotide polymorphism loci associated with systemic sclerosis susceptibility: a genetic association study in a Chinese Han population.

Chang Shu,Yun Li,Wei Wang,Hongzhong Jin,Xiaofei Mao,Nan Wu,Wei Du,Qiuning Sun,Xuming Mao,Qin Zhu,Shervin Assassi

doi:10.1371/journal.pone.0113197

Abstract

ObjectiveThe aim of this study was to confirm the association of RHOB and FAM167A-BLK gene polymorphisms with susceptibility to systemic sclerosis (SSc) in a Chinese Han population.MethodsA total of 248 SSc patients and 251 healthy controls of Chinese Han ethnicity, which visited the department of dermatology of Peking Union Medical College Hospital, were included in the study. Six selected single nucleotide polymorphisms (SNPs) in the RHOB and FAM167A-BLK regions were selected as markers and were genotyped using a MassARRAY system, which is based on the matrix-assisted laser desorption/ionization time of flight mass spectrometry technique.ResultsThree SNPs in the coding regions of the RHOB and FAM167A-BLK genes displayed an association with SSc: (1) rs1062292T, which is a newly discovered SNP in the RHOB gene (P = 0.03, odds ratio [OR] = 1.62, 95% confidence interval (CI) = 1.05–2.50), (2) rs2736340T (P = 0.03, OR = 1.39, 95%CI = 1.03–1.85), and (3) rs13277113A (P = 0.04, OR = 1.34, 95%CI = 1.01–1.76), both in the FAM167A-BLK gene. Our results support previous findings that vaiants in the RHOB and FAM167A-BLK genes may be associated with susceptibility to SSc. However, the loci of the SNPs in RHOB region that displayed an association with SSc are quite different from the loci which were identified in studies of Caucasian populations.ConclusionOur results confirm that RHOB and FAM167A-BLK polymorphisms exist in Chinese Han SSc patients. Therefore, variants of the RHOB and FAM167A-BLK genes are promising genetic markers for SSc.

Highlights

Scleroderma or systemic sclerosis (SSc) is a chronic, connective tissue disease characterized by widespread fibrosis of the skin and internal organs, small-vessel vasculopathy, and immune dysregulation with or without production of autoantibodies
Our results confirm that RHOB and FAM167A-BLK polymorphisms exist in Chinese Han SSc patients
The rs1062292T allele showed a higher prevalence in SSc patients (91.9%) than in controls (87.6%), thereby indicating a statistically significant association between the rs1062292T allele and SSc risk (P50.03, OR51.62, 95%CI51.05–2.50) in the x2 test

Summary

Introduction

Scleroderma or systemic sclerosis (SSc) is a chronic, connective tissue disease characterized by widespread fibrosis of the skin and internal organs, small-vessel vasculopathy, and immune dysregulation with or without production of autoantibodies. It is widely accepted that different genetic factors contribute to the development and prognosis of SSc. Further, GWASs have been a useful tool for studying the genetic basis of autoimmune and other complex diseases. In a recent GWAS in a French Caucasian SSc discovery cohort [5] 17 single-nucleotide polymorphisms (SNPs) displaying tier two associations were selected for follow-up in independent cohorts. Six SNPs located in three loci (TNIP1, RHOB, and PSORS1C1) were proposed as novel SSc risk factors. Later, in a large independent replication study by a Spanish group, TNIP1, but not RHOB and PSORS1C1, was confirmed to be associated with SSc [7]

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