Genetic risk factors in lupus nephritis and IgA nephropathy--no support of an overlap.
BACKGROUND
IgA nephropathy (IgAN) and nephritis in Systemic Lupus Erythematosus (SLE) are two common forms of glomerulonephritis in which genetic findings are of importance for disease development. We have recently reported an association of IgAN with variants of TGFB1. In several autoimmune diseases, particularly in SLE, IRF5, STAT4 genes and TRAF1-C5 locus have been shown to be important candidate genes. The aim of this study was to compare genetic variants from the TGFB1, IRF5, STAT4 genes and TRAF1-C5 locus with susceptibility to IgAN and lupus nephritis in two Swedish cohorts.


METHODS
We genotyped 13 single nucleotide polymorphisms (SNPs) in four genetic loci in 1252 DNA samples from patients with biopsy proven IgAN or with SLE (with and without nephritis) and healthy age- and sex-matched controls from the same population in Sweden.


RESULTS
Genotype and allelic frequencies for SNPs from selected genes did not differ significantly between lupus nephritis patients and SLE patients without nephritis. In addition, haplotype analysis for seven selected SNPs did not reveal a difference for the SLE patient groups with and without nephritis. Moreover, none of these SPNs showed a significant difference between IgAN patients and healthy controls. IRF5 and STAT4 variants remained significantly different between SLE cases and healthy controls. In addition, the data did not show an association of TRAF1-C5 polymorphism with susceptibility to SLE in this Swedish population.


CONCLUSIONS
Our data do not support an overlap in genetic susceptibility between patients with IgAN or SLE and reveal no specific importance of SLE associated SNPs for the presence of lupus nephritis.
Vuong
Mai Tuyet
MT
Rheumatology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden. maituyetvuong@gmail.com
Gunnarsson
Iva
I
Lundberg
Sigrid
S
Svenungsson
Elisabet
E
Wramner
Lars
L
Fernström
Anders
A
Syvänen
Ann-Christine
AC
Do
Lieu Thi
LT
Jacobson
Stefan H
SH
Padyukov
Leonid
L
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005922:Glomerulonephritis, IGA / Q000235:genetics*; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics; D008181:Lupus Nephritis / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D050797:STAT4 Transcription Factor / Q000235:genetics; D047990:TNF Receptor-Associated Factor 1 / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D055815:Young Adult
C431713:IRF5 protein, human; D050835:Interferon Regulatory Factors; D050797:STAT4 Transcription Factor; C508960:TGFB1 protein, human; D047990:TNF Receptor-Associated Factor 1; D053773:Transforming Growth Factor beta1