APOE gene polymorphisms in Iranian multiple sclerosis patients

Background: Multiple sclerosis, MS, is a debilitating autoimmune disease with chronic inflammatory nature that is associated with axonal demyelination in the central nervous system. Tehran, capital of Iran, has recently been faced with highly increasing rates of MS prevalence. Etiology of the disease is not elucidated yet, however, genetic linkage studies pointed to a region on ۱۹th chromosome, where APOE gene also located. Associations between APOE gene polymorphism and neurodegenerative diseases have been demonstrated, however, their role in susceptibility to MS has mainly been associated with high discrepancies. Objectives: The frequencies of APOE alleles and genotypes in Iranian MS patients and healthy controls were determined and their correlations with susceptibility to MS, EDSS disability scores, disease onset age and the disease type were investigated. Design: Case-control study Setting: Collaboration of Two MS research centers from Sina and Mostafa Khomeini hospitals and Tonekabon branch of Islamic Azad University. Patients and Methods: Blood samples were used for genotyping by PCR-RFLP method. Fifty confirmed MS patients and fifty age- and sex-matched healthy controls were entered the study. Genomic DNA was isolated and a ۲۲۷ bp segment from APOE gene was amplified. PCR products were digested by Hhal, and the resulting DNA fragments were resolved on ۱۵% polyacrylamide gel electrophoresis. APOE genotype for each individual was determined using the known electrophoretic patterns. Main Outcome Measures: Effect of APOE minor alleles (E۲ and E۴) on MS disease incidence and progression. Sample Size: Fifty definitive MS patients and ۵۰ healthy controls. Results: Frequency distribution of APOE alleles and genotypes were not statistically different between cases and controls. Subgroup analysis revealed higher frequency of e۴ allele among RRMS patients (OR: ۵.۷, P<.۰۱). Patients which were E۳E۳ homozygotes had considerably lower EDSS scores and higher disease onset age (P>.۰۵). Conclusions: APOE e۳ allele had protective effect and E۳/E۳ homozygotes had better conditions and higher onset age. Limitations: Small sample size due to the rarity of E۴/E۴ or E۲/E۲ homozygotes. Conflict of Interest: None Keywords: APOE gene, Apolipoproteins E, Multiple sclerosis genetics, Iranian people, Allele frequency, Gene polymorphism, APOE epsilon ۴, APOE epsilon ۲.

کلیدواژه ها:

APOE gene ، Apolipoproteins E ، Multiple sclerosis genetics ، Iranian people ، Allele frequency ، Gene polymorphism ، APOE epsilon ۴ ، APOE epsilon ۲