Genetic variation in the transforming growth factor-beta1 gene is associated with susceptibility to IgA nephropathy.
BACKGROUND
There is growing evidence of genetic risk for susceptibility to IgA nephropathy. Among several candidate genes related to immunological regulation in renal tissue, TGFB1 is known to be a contributor to proliferation and the development of fibrosis.


METHODS
We analysed several SNPs in a region of this gene using 212 DNA samples from biopsy-proven IgA nephropathy patients, 146 men and 66 women and 477 healthy age-matched controls (321 men and 156 women) from the same population in Sweden.


RESULTS
Frequencies of four out of five selected SNPs (rs6957, rs2241715, rs1800471, rs1982073 and rs1800469) were found to significantly differ between male patients and male controls in a co-dominant model (corrected P <or= 0.05) and of two SNPs (rs1982073 and rs1800469) in the allelic model (P <or= 0.05 in 100,000 permutation test). Haplotype analysis for five selected SNPs revealed a significant association of TGGCG with protective effect (P = 0.0012, empirical P = 0.006, 100,000 permutations) and of CTGTA with susceptibility effect (P = 0.0018, empirical P = 0.008, 100,000 permutations). In our study, no association with TGFB1 variations was found when comparing female patients and female controls. No association was found for TGFB1 markers with disease progression for selected individuals from the patient's group. In addition, meta-analysis performed for SNP rs1982073 for combined patients and controls from our study together with published data from two independent studies showed a significant association.


CONCLUSIONS
Our experimental data together with the meta-analysis suggest TGFB1 as an important candidate gene for further biological studies of IgA nephropathy and as a possible target for therapy. Our data also indicate a possibility of a gender effect in the genetic background of IgA nephropathy.
Vuong
Mai Tuyet
MT
Department of Medicine, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
Lundberg
Sigrid
S
Gunnarsson
Iva
I
Wramner
Lars
L
Seddighzadeh
Maria
M
Hahn-Zoric
Mirjana
M
Fernström
Anders
A
Hanson
Lars A
LA
Do
Lieu Thi
LT
Jacobson
Stefan H
SH
Padyukov
Leonid
L
D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005922:Glomerulonephritis, IGA / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D055815:Young Adult
D053773:Transforming Growth Factor beta1