Association analysis of PON2 genetic variants with serum paraoxonase activity and systemic lupus erythematosus

BMC Medical Genetics

Research Article

M Ilyas Kamboh¹  Candace M Kammerer¹  Amy S Dressen¹  F Yesim Demirci¹  Sudeshna Dasgupta¹  Amy H Kao²  Susan Manzi³  Rosalind Ramsey-Goldman⁴  Elisa Y Rhew⁴ 

[1] Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA;Division of Rheumatology and Clinical Immunology, Lupus Center of Excellence, Pittsburgh, PA, USA;Division of Rheumatology and Clinical Immunology, Lupus Center of Excellence, Pittsburgh, PA, USA;West Penn Allegheny, Pittsburgh, PA, USA;Division of Rheumatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA;

关键词: Systemic Lupus Erythematosus;    Systemic Lupus Erythematosus Patient;    Lupus Nephritis;    Modest Association;    Systemic Lupus Erythematosus Case;   

DOI  :  10.1186/1471-2350-12-7

 received in 2010-07-23, accepted in 2011-01-11,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundLow serum paraoxonase (PON) activity is associated with the risk of coronary artery disease, diabetes and systemic lupus erythematosus (SLE). Our prior studies have shown that the PON1/rs662 (p.Gln192Arg), PON1/rs854560 (p.Leu55Met), PON3/rs17884563 and PON3/rs740264 SNPs (single nucleotide polymorphisms) significantly affect serum PON activity. Since PON1, PON2 and PON3 share high degree of structural and functional properties, in this study, we examined the role of PON2 genetic variation on serum PON activity, risk of SLE and SLE-related clinical manifestations in a Caucasian case-control sample.MethodsPON2 SNPs were selected from HapMap and SeattleSNPs databases by including at least one tagSNP from each bin defined in these resources. A total of nineteen PON2 SNPs were successfully genotyped in 411 SLE cases and 511 healthy controls using pyrosequencing, restriction fragment length polymorphism (RFLP) or TaqMan allelic discrimination methods.ResultsOur pair-wise linkage disequilibrium (LD) analysis, using an r2cutoff of 0.7, identified 14 PON2 tagSNPs that captured all 19 PON2 variants in our sample, 12 of which were not in high LD with known PON1 and PON3 SNP modifiers of PON activity. Stepwise regression analysis of PON activity, including the known modifiers, identified five PON2 SNPs [rs6954345 (p.Ser311Cys), rs13306702, rs987539, rs11982486, and rs4729189; P = 0.005 to 2.1 × 10-6] that were significantly associated with PON activity. We found no association of PON2 SNPs with SLE risk but modest associations were observed with lupus nephritis (rs11981433, rs17876205, rs17876183) and immunologic disorder (rs11981433) in SLE patients (P = 0.013 to 0.042).ConclusionsOur data indicate that PON2 genetic variants significantly affect variation in serum PON activity and have modest effects on risk of lupus nephritis and SLE-related immunologic disorder.

【 授权许可】

Unknown   
© Dasgupta et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.