Genetic variation in the paraoxonase-3 (PON3) gene is associated with serum PON1 activity.
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.
Sanghera
Dharambir K
DK
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Manzi
Susan
S
Minster
Ryan L
RL
Shaw
Penny
P
Kao
Amy
A
Bontempo
Franklin
F
Kamboh
M Ilyas
MI
D000328:Adult; D001741:Black or African American; D000483:Alleles; D017152:Antibodies, Antiphospholipid / Q000235:genetics; D043303:Aryldialkylphosphatase / Q000097:blood*; D002340:Carotid Artery Diseases / Q000235:genetics; D016022:Case-Control Studies; D004950:Esterases / Q000235:genetics*; D005787:Gene Frequency; D014644:Genetic Variation; D006801:Humans; D007249:Inflammation / Q000235:genetics; D016014:Linear Models; D008180:Lupus Erythematosus, Systemic / Q000235:genetics; D008181:Lupus Nephritis / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012044:Regression Analysis; D012307:Risk Factors; D014481:United States; D044465:White People
D017152:Antibodies, Antiphospholipid; D004950:Esterases; D043303:Aryldialkylphosphatase; C113656:PON3 protein, human