Premium
3′ polymorphisms of ETS1 are associated with different clinical phenotypes in SLE
Author(s) -
Sullivan Kathleen E.,
Piliero Lisa M.,
Dharia Tushar,
Goldman Daniel,
Petri Michelle A.
Publication year - 2000
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/1098-1004(200007)16:1<49::aid-humu9>3.0.co;2-z
Subject(s) - biology , phenotype , genetics , ets1 , clinical phenotype , gene , transcription factor
Abstract A microsatellite repeat polymorphism was identified in the 3′ flanking region of the human ETS1 gene. Sequencing revealed two CA repeat segments in close proximity. Seven different alleles comprising various combinations of CA repeat units were identified in a healthy control population. Because E TS 1 plays a role in lymphocyte development and function, apoptosis, and inflammation, we examined whether any of these polymorphisms were associated with a systemic inflammatory condition, systemic lupus erythematosus (SLE). Inheritance of this disease is polygenic and a recent genome‐wide screen for SLE susceptibility loci revealed linkage with chromosome 11q14‐23, the region in which the ETS1 gene lies. This region has also been identified as a general autoimmune susceptibility region. None of the seven distinct ETS1 alleles appeared statistically more frequently in SLE patients than controls, however, two alleles were associated with particular clinical manifestations. Allele 1 is associated with discoid lesions and allele 7 is associated with vasculitis. While this polymorphism does not directly affect the coding region of E TS 1, it may be a marker for overexpression of a particular isoform or inheritance of another polymorphism which does affect function. These data suggest that E TS 1 may be involved in the phenotypic expression of systemic lupus erythematosus. Hum Mutat 16:49–53, 2000. © 2000 Wiley‐Liss, Inc.