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Genetic variation in the paraoxonase-3 (PON3) gene is associated with serum PON1 activity
Journal article   Peer reviewed

Genetic variation in the paraoxonase-3 (PON3) gene is associated with serum PON1 activity

Dharambir K Sanghera, Susan Manzi, Ryan L Minster, Penny Shaw, Amy Kao, Franklin Bontempo and M Ilyas Kamboh
Annals of human genetics, v 72(Pt 1), pp 72-81
Jan 2008
DOI: https://doi.org/10.1111/j.1469-1809.2007.00400.x
PMID: 17900266
Featured in Collection :   UN Sustainable Development Goals @ Drexel
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https://doi.org/10.1111/j.1469-1809.2007.00400.xView
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Abstract

Adult African Americans Alleles Antibodies, Antiphospholipid - genetics Aryldialkylphosphatase - blood Carotid Artery Diseases - genetics Case-Control Studies Esterases - genetics European Continental Ancestry Group Gene Frequency Genetic Variation Humans Inflammation - genetics Linear Models Lupus Erythematosus, Systemic - genetics Lupus Nephritis - genetics Middle Aged Polymorphism, Single Nucleotide Regression Analysis Risk Factors United States
Low serum paraoxonase1 (PON1) activity determined by paraoxon substrate is associated with coronary heart disease (CHD), diabetes and systemic lupus erythematosus (SLE) risk. In this investigation, we have examined the role of genetic variation in the PON3 gene in relation to PON1 activity and SLE risk in a biracial sample comprising 377 SLE patients and 482 controls from US whites and blacks. We genotyped six PON3 tagging single nucleotide polymorphisms (tagSNPs) and examined their associations with PON1 activity, SLE risk, antiphopholipid autoantibodies (APA), lupus nephritis, carotid vascular disease, and inflammation. With the exception of PON1 activity, no other significant associations were found with PON3 SNPs. Multiple regression analysis including all six PON3 tagSNPs and PON1/Q192R and L55M SNPs revealed significant association of PON1 activity with 4 SNPs: PON3/A10340C (p < 0.0001), PON3/A2115T (p = 0.002), PON1/L55M (p < 0.0001) and PON1/Q192R (p < 0.0001). These four SNPs explained 2%, 1%, 8% and 19% of the variation in PON1 activity, respectively. In summary, our new data indicate that genetic variation in the PON3 gene influences serum PON1 activity independently of the known effect of PON1 genetic variation. To our knowledge, this is the first study reporting the association of the PON3 gene variants with PON1 activity.

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Web of Science research areas
Genetics & Heredity
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