title: Epistatic interaction between genetic variants in susceptibility gene ETS1 correlates with IL-17 levels in SLE patients.
abstract: T-helper cells that produce IL-17 (Th17 cells) are a subset of CD4(+) T-cells with pathological roles in autoimmune diseases including systemic lupus erythematosus (SLE), and ETS1 is a negative regulator of Th17 cell differentiation. Our previous work on genome-wide association study (GWAS) identified two variants in the ETS1 gene (rs10893872 and rs1128334) as being associated with SLE. However, like many other risk alleles for complex diseases, little is known on how these genetic variants might affect disease pathogenesis. In this study, we examined serum IL-17 levels from 283 SLE cases and observed a significant correlation between risk variants in ETS1 and serum IL-17 concentration in patients, which suggests a potential mechanistic link between these variants and the disease. Furthermore, we found that the two variants act synergistically in influencing IL-17 production, with evidence of significant genetic interaction between them as well as higher correlation between the haplotype formed by the risk alleles and IL-17 level in patient serum. In addition, the correlation between ETS1 variants and IL-17 level seems to be more significant in SLE patients manifesting renal involvement, dsDNA autoantibody production or early-onset.
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, LKS Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Hong Kong.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.forename: Dingge
authors.initials: D
authors.lastname: Ying
authors.forename: Shuai
authors.initials: S
authors.lastname: Zeng
authors.forename: Tsz Leung
authors.initials: TL
authors.lastname: Lee
authors.forename: Chak Sing
authors.initials: CS
authors.lastname: Lau
authors.forename: Tak Mao
authors.initials: TM
authors.lastname: Chan
authors.forename: Alexander Moon Ho
authors.initials: AM
authors.lastname: Leung
authors.forename: Chi Chiu
authors.initials: CC
authors.lastname: Mok
authors.forename: Sik Nin
authors.initials: SN
authors.lastname: Wong
authors.forename: Ka Wing
authors.initials: KW
authors.lastname: Lee
authors.forename: Marco Hok Kung
authors.initials: MH
authors.lastname: Ho
authors.forename: Pamela Pui Wah
authors.initials: PP
authors.lastname: Lee
authors.forename: Brian Hon-Yin
authors.initials: BH
authors.lastname: Chung
authors.forename: Chun Yin
authors.initials: CY
authors.lastname: Chong
authors.forename: Raymond Woon Sing
authors.initials: RW
authors.lastname: Wong
authors.forename: Mo Yin
authors.initials: MY
authors.lastname: Mok
authors.forename: Wilfred Hing Sang
authors.initials: WH
authors.lastname: Wong
authors.forename: Yu Lung
authors.initials: YL
authors.lastname: Lau
authors.forename: Wanling
authors.initials: W
authors.lastname: Yang
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D004843:Epistasis, Genetic; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006239:Haplotypes; D006723:Hong Kong / Q000453:epidemiology; D006801:Humans; D020381:Interleukin-17 / Q000097:blood*; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000453:epidemiology / Q000235:genetics*; D016017:Odds Ratio; D015995:Prevalence; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics*; D055815:Young Adult
chemical_list: D020381:Interleukin-17; D050784:Proto-Oncogene Protein c-ets-1
keywords: ETS1; IL‐17; SLE; epistasis