Arg206Cys substitution in DNASE1L3 causes a defect in DNASE1L3 protein secretion that confers risk of systemic lupus erythematosus.

ABSTRACT:

Objectives

To determine if the polymorphism encoding the Arg206Cys substitution in DNASE1L3 explains the association of the DNASE1L3/PXK gene locus with systemic lupus erythematosus (SLE) and to examine the effect of the Arg206Cys sequence change on DNASE1L3 protein function.

Methods

Conditional analysis for rs35677470 was performed on cases and controls with European ancestry from the SLE Immunochip study, and genotype and haplotype frequencies were compared. DNASE1L3 protein levels were measured in cells and supernatants of HEK293 cells and monocyte-derived dendritic cells expressing recombinant and endogenous 206Arg and 206Cys protein variants.

Results

Conditional analysis on rs35677470 eliminated the SLE risk association signal for lead single-nucleo

SUBMITTER: Coke LN 

PROVIDER: S-EPMC8142439 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature