Document Detail


Paraoxonase gene polymorphism and serum activity in progressive IgA nephropathy.
MedLine Citation:
PMID:  17173245     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: HDL-associated paraoxonase (PON1) reduces oxidation of lipids in LDL, and activity is inversely related to coronary heart disease risk with a beneficial effect on the development of atherosclerosis. Risk factors associated with atherosclerosis, such as hypertension, dyslipidemia and smoking, also promote the progression of chronic glomerulonephritides which may therefore be associated with perturbations in PON1 activity. METHODS: We performed a genetic association study in patients with IgA nephropathy (IgAN) (n=115) compared with control subjects (n=118). The aim was to test whether polymorphisms in the PON1 coding region (Q192R and L55M) and its promoter (-108C/T and -162A/G) are associated with either IgAN or with the progression. We measured serum paraoxonase activity in 60 out of 115 patients. All patients had been followed up for more than 4 years. RESULTS: There were no differences in the genotype frequency at 3 of the polymorphic sites (Q192R, L55M and -108C/T) between the patients and controls. However, the frequency distribution at -162 position (A/G) was significantly diffe-rent in IgAN (p=0.028, chi-square test) with a higher frequency of the heterozygote (0.017, Fisher exact test [FE]; odds ratio [OR] = 1.99; 95% confidence interval [95% CI], 1.14-3.47). Although there were no differences in the genotype frequency at 3 of the polymorphic sites (Q192R, L55M and -162C/T) between the patients with progressive IgA and the nonprogressive patients, we found that the frequency of the C allele for the -108C/T polymorphism was elevated in those patients with nonprogressive disease (n=85) compared with those with progressive disease (n=30) (61% vs. 47%; p=0.070, FE; OR=1.75, 95% CI, 0.97-3.18). Furthermore, PON1 activity was significantly higher in nonprogressive patients compared with progressors (206 +/- 71 vs. 136 +/- 48; p<0.001), and activity significantly correlated with 1/serum creatinine (SCr) (p<0.001; r=0.38). CONCLUSIONS: The results of this study suggest that in IgAN, lower PON1 activity may be associated with the deterioration of kidney function. This could be due to variable expression of the PON1 gene, or a functional effect of the gene product.
Authors:
Tibor J Kovács; Shelley Harris; Tibor K Vas; Ildikó Seres; Colin D Short; István K Wittmann; György Paragh; Michael I Mackness; Bharti Mackness; Paul N Durrington; Judit M Nagy; Paul E C Brenchley
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Publication Detail:
Type:  Clinical Trial; Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of nephrology     Volume:  19     ISSN:  1121-8428     ISO Abbreviation:  J. Nephrol.     Publication Date:    2006 Nov-Dec
Date Detail:
Created Date:  2006-12-18     Completed Date:  2007-04-05     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9012268     Medline TA:  J Nephrol     Country:  Italy    
Other Details:
Languages:  eng     Pagination:  732-8     Citation Subset:  IM    
Affiliation:
Second Department of Medicine and Nephrological Centre, University of Pecs, Pecs, Hungary.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aryldialkylphosphatase / genetics*,  metabolism
Disease Progression
Female
Follow-Up Studies
Gene Expression Regulation, Enzymologic* / genetics
Genotype
Glomerulonephritis, IGA / enzymology,  genetics*
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide*
Chemical
Reg. No./Substance:
EC 3.1.8.1/Aryldialkylphosphatase; EC 3.1.8.1/PON1 protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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