Association of angiotensin converting enzyme type 2 serum level and gene polymorphisms with multiple sclerosis

血管紧张素转换酶2型血清水平和基因多态性与多发性硬化症的关联

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Abstract

Multiple sclerosis (MS) is the most prevalent autoimmune neurodegenerative heterogeneous disease affecting young adults, and angiotensin-converting enzyme 2 (ACE2) is a potential biomarker in MS. To compare serum levels of ACE2 between MS patients and healthy controls, and to investigate the relationships between ACE2 gene polymorphisms (rs2074192 and rs2285666) and MS susceptibility and clinical characteristics in a Jordanian population. A case-control study was conducted. Enzyme-linked immunosorbent assay (ELISA) was used to measure ACE2 levels in the serum of 88 MS patients and 87 controls. Genotyping of rs2074192 and rs2285666 polymorphisms was performed for 498 MS patients and 504 healthy controls by Illumina HiSeq xTen system (Illumina Platform) technique. Genetic analyses were sex-stratified and used X-chromosome–appropriate coding, with Hardy–Weinberg equilibrium assessed in females only. After adjustment for covariates, log(ACE2) serum levels were significantly higher in MS patients compared to healthy controls (p < 0.001). The ACE2 rs2074192 TT genotype (p = 0.003), and T allele (p < 0.001) are significantly associated with cases. Significant associations were found between cases and the ACE2 rs2285666 CC genotype (p = 0.037), and C allele (p = 0.040). Significant associations were revealed between rs2074192 genotype and EDSS level (p = 0.036), and between rs2285666 genotype and current treatment with DMT (p = 0.022). MS patients had higher ACE2 serum levels than healthy controls and ACE2 is a susceptibility gene for MS in the Jordanian population.

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