Apolipoprotein E Gene Polymorphisms in Saudi Patients with Systemic Lupus Erythematosus

Abstract

Apolipoprotein E (APOE) is a glycosylated protein with multiple biological properties. APOE gene polymorphism plays a central role in lipid metabolism and has recently been suggested to regulate inflammation. Our objective is to evaluate whether APOE polymorphism affects susceptibility to SLE. APOE genotyping was performed using ApoE StripAssay™ kit. Results indicated significantly higher frequencies of allele ε4 and genotype ε3/ε4 and lower frequencies of allele ε3 and genotype ε3/ε3 in SLE patients than controls. APOE ε2 allele was found in three patients, whereas it was absent in controls. The frequencies of allele ε4 and genotype ε3/ε4 were significantly higher in SLE patients with renal involvement and those of alleles ε2, ε4 and genotypes ε2/ε3, ε3/ε4 were higher in patients with neuropsychiatric symptoms. It is concluded that APOE allele ε4 is associated with susceptibility risk/clinical manifestations of SLE and ε2 may increase its severity while ε3 is protective for SLE in Saudis.

The genetic link between systemic autoimmune disorders and temporal lobe epilepsy: A bioinformatics study

“…35 Another study concluded that APOE allele ε4 is associated with susceptibility risk/clinical manifestations of SLE. 38 Finally, a previous study suggested that APOE ε4 presence leaves patients with IDDM more susceptible to cognitive decline at a younger age, possibly through vascular pathways. 39 Previous studies have also found that APOE ε4 has associations with TLE (e.g., nonlesional mesial temporal lobe epilepsy) via various mechanisms (e.g., amyloid deposition in the brain and impairment of nerve damage repair mechanisms).…”

“…The first SNP was rs16944 on the Interleukin-1β (IL-1β) gene; different studies reported the associations between this gene variation and TLE, 27 RA, 28,29 SLE, 30 and IDDM. 31 The second genetic variation was ε4 variation of apolipoprotein E (APOE) gene that was associated with TLE, [32][33][34] RA, 35,36 SLE, 37,38 and IDDM. 39,40 None of the above references and studies had patients with serologically proven autoimmune epilepsy.…”

“…APOE ε4 is a variant of APOE protein that is associated with SLE, RA, and IDDM probably due to its disrupting effects on the oxidant defense and vascular functions. [34][35][36][37][38][39][40] One study showed that APOE genotypes are strongly linked to inflammation and lipid levels in people with RA. 35 Another study concluded that APOE allele ε4 is associated with susceptibility risk/clinical manifestations of SLE.…”

Lupus nephritis: A focus on the United Arab Emirates and the potential role of genetics

“…Genetic studies of SLE among Arab patients in the GCC region are generally scarce in the literature, and extremely rare regarding LN. Some of SLE susceptibility genes have been recently reported and/or investigated in SLE patients in the GCC region, such as HLA alleles, 29,30 C1Q, 31,32 ISG15, 33 APOE, 34 PTEN, 35 and PNP 36 genes in Saudi patients; and IRF5, 37 PTPN22, 38 ACE, 39 eNOS, 40,41 and CTLA4 42,43 genes in Kuwaiti patients. Of note, Al-Mayouf et al 44 identified a rare autosomal recessive monogenic form of SLE in Arab patients in Saudi Arabia, caused by a null mutation in the DNASE1L3 gene, and correlated with a high frequency of LN.…”

Dietary Supplementation With Eicosapentaenoic Acid Inhibits Plasma Cell Differentiation and Attenuates Lupus Autoimmunity

“…It has also been reported that 36% of patients with newly diagnosed SLE have hypercholesterolemia (3), suggesting a relationship between the dysregulation of lipid metabolism and autoimmune responses. Consistently, recent genome-wide association studies and expression quantitative trait loci analyses have revealed that genes involved in lipid metabolism increase the susceptibility to autoimmune diseases such as rheumatoid arthritis and SLE (4)(5)(6). However, the molecular mechanism by which lipid metabolism influences the pathology of SLE is unclear.…”