Synergism between apolipoprotein E Ɛ4 allele and paraoxonase (PON1) 55-M allele is associated with risk of systemic lupus erythematosus

Clin Rheumatol. 2018 Apr;37(4):971-977. doi: 10.1007/s10067-017-3859-3. Epub 2017 Dec 22.

Abstract

Evidences indicate that abnormal lipid metabolism and lipid peroxidation can affect the progression of complications in systemic lupus erythematosus (SLE) patients. Apolipoprotein E (ApoE) and paraoxonase-1 (PON1) play important role in lipid metabolism and protection of lipid peroxidation. The polymorphisms of ApoE and paraoxonase (PON1) L55M (Met < Leu) allele genes lead to disorders in lipid metabolism and are related to atherosclerosis. This study is the first investigation to examine the possible association between ApoE and PON1-L55M polymorphisms and correlation with serum arylesterase (ARE) activities of PON, levels of malondialdehyde (MDA), neopterin, and lipid lipoprotein in SLE patients from Iranian western population. The present case-control study consisted of 107 SLE patients and 101 gender- and age-matched, unrelated, healthy controls from Iran's western population. The ApoE and PON1-L55M genotypes were identified using PCR-RFLP method. The serum level of MDA, neopterin, lipid levels, and ARE activity were determined by HPLC, commercial kits, and spectrophotometry, respectively. Our results showed that ApoE ε4 and PON1-55M alleles act synergistically to increase the risk of SLE by 1.47 times (p = 0.038). We found that the frequency of ApoE Ɛ3/Ɛ4 genotype was higher in SLE patients (11.2%) compared with control subjects (5%), although the difference was not significant (p = 0.087). This study for the first time not only demonstrates that ApoE Ɛ4 and PON-55M alleles synergistically increase the risk of SLE but also reveals that serum levels of MDA, neopterin, and LDL-C are high in SLE patients. This information may be in value for evaluating SLE progression and in the elucidation of the mechanisms of the disease pathogenesis.

Keywords: Apolipoprotein E genotypes; Arylesterase activity of paraoxonase; Malondialdehyde; Neopterin; Paraoxonase (PON1)-55 polymorphism; Systemic lupus erythematosus.

MeSH terms

  • Adult
  • Alleles*
  • Apolipoprotein E4 / genetics*
  • Aryldialkylphosphatase / genetics*
  • Carboxylic Ester Hydrolases / blood
  • Case-Control Studies
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Iran
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / genetics*
  • Male
  • Malondialdehyde / blood
  • Middle Aged
  • Neopterin / blood
  • Polymorphism, Single Nucleotide
  • Young Adult

Substances

  • Apolipoprotein E4
  • Malondialdehyde
  • Neopterin
  • Carboxylic Ester Hydrolases
  • arylesterase
  • Aryldialkylphosphatase