The relationship of APOE genetic polymorphism with susceptibility to multiple sclerosis and its clinical phenotypes in Kuwaiti Arab subjects
Introduction
The pattern of APOE polymorphism is believed to confer susceptibility to a variety of disorders including dyslipidaemia, Alzheimer's disease, coronary heart disease (CHD) [1], [2], and probably, multiple sclerosis (MS) and schizophrenia [3], [4], [5], [6], [7], [8]. The link of APOE with neurological disease may be due to the fact that it is involved in neuronal growth and repair essentially by mediating growth in the telencephalic hippocampal region [9].
Multiple sclerosis (MS) typically results in demyelination and varying degrees of axonal pathology with progressive neurological dysfunction. The APOE gene is located in chromosome 19q, the same region described recently as a susceptibility region for MS [10]. There are recent reports that, in MS (i) the concentration of apo E in CSF and its intrathecal synthesis is reduced [11]; (ii) apo E4 is associated with significantly faster progression of disability [3], [12] and more extensive tissue destruction or less effective tissue repair [13].
The frequency of each apo E isoform varies with geographical region, race, and ethnicity, and the association between apo E polymorphism and disease is not always consistent. There is little information on APOE and susceptibility to MS in the Gulf Arab population. This study explored the relationship between APOE polymorphism and susceptibility to, and clinical phenotypes of, MS among Kuwaiti Gulf Arab subjects, in whom the prevalence of MS is low [14].
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Subjects
Thirty-nine patients with clinical evidence of MS (17 M, 22 F) were recruited into the study after voluntary informed consent. The patients attended the Neurology Clinic at the Mubarak Al-Kabeer Teaching Hospital in Kuwait—the major referral centre for the whole of the Emirate.
The clinical diagnosis of MS in each case was based on Poser et al.'s [15] criteria. The extent of disability was assessed by Kurtzke's expanded disability scale (EDSS) [16], and the severity of disease was calculated as
Clinical and demographic parameters
At diagnosis, the men and women had respective mean (S.D.) ages of 36.8 (11.1) and 33.2 (9.5) y. The age at initial diagnosis (range 9–53 y) was ≤20 y in 6 (20.7%), and >20 y in 23 (79.3%) patients. Most of the subjects were Kuwaiti Arabs [n=34 (87.2%)]; there were 4 (10.3%) non-Kuwaiti Arabs and 1 (2.6%) Asian. The most common presenting symptoms were unilateral visual loss or blurring (28.2%), numbness and paraesthesiae of legs, arms, face, and/or multiple sites (33.4%), diplopia (7.7%), and
Discussion
Among Kuwaitis, the prevalence rate for MS is about 9.2/100,000 [14], which is much lower than that found in other Arabs or in Caucasians. This relatively low prevalence rate is believed to be due to a variety of yet unexplained genetic causes [13]. Despite this low frequency, MS constitutes a significant burden of care in Kuwait, and it is of great interest in the country to evaluate its potential genetic associations.
The relationship between APOE polymorphism and susceptibility to MS and its
Acknowledgements
We gratefully acknowledge the help of clinical and laboratory colleagues at the Mubarak Al Kabeer Hospital and Kuwait University Faculty of Medicine, Kuwait. These studies were supported by a Kuwait University Research Administration Grant # MG 02/02 (SAS, AOA).
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Cited by (20)
Association between apolipoprotein E gene polymorphism and the risk of multiple sclerosis: A meta-analysis of 6977 subjects
2012, GeneCitation Excerpt :In addition, two publications were excluded for poor quality and six for insufficient data for calculation of an OR and 95% CI. Therefore, 20 studies were included in the final meta-analysis (Al-Shammri et al., 2005; Ballerini et al., 2000; Carlin et al., 2000; Cocco et al., 2005; Ferri et al., 1999; Gaillard et al., 1998; Høgh et al., 2000; Koutsis et al., 2007; Losonczi et al., 2010; Mehta et al., 2003; Mustafina et al., 2008; Niino et al., 2003; Pinholt et al., 2005; Pirttilä et al., 2000; Ramsaransing et al., 2005; Rubinsztein, 1994; Savettieri et al., 2003; Weatherby et al., 2000; Zakrzewska-Pniewska et al., 2004; Zwemmer et al., 2004), which contained 4080 MS cases and 2897 controls. Table 1 shows the studies identified and their main characteristics.
Apolipoprotein e polymorphisms status in Iranian patients with multiple sclerosis
2012, Journal of the Neurological SciencesCitation Excerpt :They found a greater frequency of E4E4 in the MS population which suggested APOE-ε4 as a risk factor for MS or clinical progression [31]. Also this homozygote genotype has been found in patients from Sweden [38] and Kuwait [35]. In this study, we found that APOE-ε2ε3 genotype and/or APOE-ε2 allele may have a protective role in MS development.
No association between APOE epsilon 4 allele and multiple sclerosis susceptibility: A meta-analysis from 5472 cases and 4727 controls
2011, Journal of the Neurological SciencesCitation Excerpt :All analyses were performed using STATA software, version 10.0 (Stata Corporation, College Station, TX, USA). A total of 27 [19–21,24,27–49] relevant studies concerning the APOE ε2, 4 alleles and MS were identified. Seven studies [19,21,43–47] were excluded due to the number of alleles that couldn't be extracted.
The genetics of clinical outcome in multiple sclerosis
2008, Journal of NeuroimmunologyThe impact of our genes: Consequences of the apolipoprotein E polymorphism in Alzheimer disease and multiple sclerosis
2006, Journal of the Neurological Sciences