Paraoxonase (PON1) gene polymorphisms in Fabry disease: correlation with renal disease.
BACKGROUND
Fabry disease is associated with cardiomyopathy, early-onset stroke, and progressive renal failure, and other features. No markers predict multisystemic disease progression. The hypothesis of the current study is to assess a clinically relevant marker for Fabry disease using polymorphic genotyping of a marker that has been shown to be involved in interrelated cardiac, vascular, and renal abnormalities in patients not affected by Fabry disease. The paraoxonase (PON1) polymorphisms, Leu55Met and Gln192Arg, modulate intima-medial artery thickening, prognosis of cardiovascular stroke, and renal failure in other diseases.


METHODS
PON1 polymorphisms were ascertained. The Mainz Severity Score Index (MSSI) for Fabry disease was calculated. Local Institutional Review Board approval was received.


RESULTS
104 patients (58 female) and 46 controls (23 female) were evaluated. There was a significant difference (p = 0.04) in PON55LL (42.3%) among patients as compared to controls (21.7%) but none in PON192 genotypes. PON55 variant (MM) was correlated with severe MSSI renal sub-scores (p < 0.001) also when age-adjusted but not with cardiac, neurological, or general sub-scores. PON55LL genotype, correlated with higher PON1 activity, had lowest α-galactosidase-A activity (n = 45).


CONCLUSIONS
There was no combined effect of PON55-PON192 polymorphisms. PON55LL was more common among patients. PON55MM genotype was correlated with non-mild renal sub-scores. However, sample size needs to be enlarged.
Shemesh
Tamar
T
Gaucher Clinic, Shaare Zedek Medical Center, Jerusalem, Israel.
Whybra
Catharina
C
Delgado-Sanchez
Sandra
S
Beck
Michael
M
Elstein
Deborah
D
Altarescu
Gheona
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D043303:Aryldialkylphosphatase / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D000795:Fabry Disease / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D007674:Kidney Diseases / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D055815:Young Adult
D005819:Genetic Markers; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human