The study of synergistic effects of paraoxonase (pon1) 55 m allele and of buche non-uu phenotype on the risk of systemic lupus erythematosus: influence on lipid and lipoprotein metabolism and oxidativ

Farzane Lotfi,1,* Asad vaisi-raygani ,2 Fariborz bahrehmand ,3

1. Department of Clinical Biochemistry, Kermanshah University of Medical Sciences
2. Fertility and Infertility Research Center, Kermanshah University of Medical Sciences
3. Kermanshah University of Medical Sciences

Abstract

Introduction

There is some evidence indicating lipid peroxidation can affect progression of atherosclerosis, cardiovascular diseases (cvds) and glomerulonephritis in systemic lupus erythematosus (sle) patients. human butyrylcholinesterase (buche) and paraoxonase-1 (pon1) are two major bioscavenger enzymes that are associated with inflammation, oxidative stress and lipid metabolism. hyperlipidemia, increase in lipid oxidation reactions and defects in antioxidant status may lead to increased oxidative stress and high frequency of cvds in sle. it has also been suggested that deficiency in the function of the antioxidant system and an increase in reactive oxygen release (ros) may play an important role in the pathogenesis of sle. this study is the first investigation to examine the association of buche phenotypes, pon1 (l55m; pon-55-m) polymorphism, the levels of malondialdehyde (mda), neopterin, lipid-lipoprotein and activities of buche and arylesterase activity (are) of pon with severity of sle.

Methods

The present case-control study consisted of 109 sle patients and 101 gender- and age-matched, unrelated healthy control subjects from the population of west iran. buche activity with its phenotypes and are activity of pon1 were measured by spectrophotometry. the pon1 55 met>leu (m>l) polymorphism was detected by pcr-rflp. plasma mda and serum neopterin was measured by hplc. plasma lipids levels were measured by the standard enzymatic method.

Results

We found that the pon-55-m allele and buche non-uu act synergistically to increase the risk of sle by 2.5 times (1.03-6.7, p = 0.044). there was a significant negative correlation between severity of sle with serum buche activity (r = -0.31, p < 0.001) and positive correlation with serum neopterin level. the sle patients with the pon-55-m (m/l + m/m) allele or with buche non-uu phenotype had significantly lower serum are and buche activities than those with pon-55-l/l or buche-uu phenotypes, respectively. in addition, their serum levels of mda, neopterin and ldl-c were significantly elevated, suggesting that these individuals are more susceptible to cvd.

Conclusion

Our findings indicated that the buche non-uu phenotype and pon 55m allele are significant risk factors for sle. we have demonstrated that the buche non-uu phenotype synergistically increases the risk of sle in individuals carrying the pon-55m allele. the carriers of m allele or non-uu buche phenotype have distinctly reduced serum are activity and elevated serum levels of mda, neopterin and ldl-c, suggesting that these individuals may be more susceptible to oxidative stress, impairment of the antioxidant system, abnormal lipid metabolism, bp, cvd and myocardial infarction. however, because of the heterogeneous picture of sle and the influence of a subset of risk factors in the development of the disease, further studies are needed to shed light on the contribution of the m allele of pon1 and non-u phenotypes of buche in the development of sle in different ethnicities.

Keywords

Butyrylcholinesterase; arylesterase; pon1 ; sle