Fibrosis-associated single-nucleotide polymorphisms in TGFB1 and CAV1 are not associated with the development of nephrogenic systemic fibrosis.
OBJECTIVE
To test the hypothesis that the subset of patients with impaired renal function who are exposed to gadolinium-containing contrast agents (GCCAs) and develop nephrogenic systemic fibrosis (NSF) have a genetic predisposition for disease.


METHODS
We examined whether an intronic single-nucleotide polymorphism (SNP) in caveolin-1 (CAV1 rs4730751) and 2 coding SNPs in transforming growth factor-beta 1 (TGFB1 rs1800471, codon 25; and rs1800470, codon 10) were associated with the NSF phenotype.


RESULTS
Forty-one patients with a history of chronic kidney disease and GCCA administration were studied, including NSF cases (n = 17) and control subjects (n = 24) without clinical or histological evidence of NSF. No significant differences in the genotype frequencies at these SNPs in TGFB1 and CAV1 were found between patients with NSF and subjects without NSF.


CONCLUSIONS
We conclude that polymorphisms in the genes encoding TGFB1 and CAV1 previously associated with the development and progression of fibrosis in several organ systems are not associated with development of NSF in this cohort of patients with renal impairment after GCCA exposure.
Pathology Service, Diagnostic Molecular Pathology Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Long P
LP
Le
Lilit
L
Garibyan
Daniel
D
Lara
Karin E
KE
Finberg
A John
AJ
Iafrate
Lyn M
LM
Duncan
Jonathan
J
Kay
Rosalynn M
RM
Nazarian
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D051242:Caveolin 1 / Q000235:genetics*; D016009:Chi-Square Distribution; D003062:Codon; D003287:Contrast Media / Q000009:adverse effects; D005260:Female; D005355:Fibrosis; D005682:Gadolinium / Q000009:adverse effects; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007438:Introns; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D054989:Nephrogenic Fibrosing Dermopathy / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
C495540:CAV1 protein, human; D051242:Caveolin 1; D003062:Codon; D003287:Contrast Media; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D005682:Gadolinium