The relationship of APOE genetic polymorphism with susceptibility to multiple sclerosis and its clinical phenotypes in Kuwaiti Arab subjects

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Abstract

Background

The possible pathogenetic relationship between APOE genetic polymorphism and susceptibility to a variety of neurodegenerative disorders, including multiple sclerosis, is controversial. Previous studies have been conducted in Caucasian subjects, with little or no data on subjects from the Arabian Gulf. We compared the frequencies of specific APOE genotypes and alleles in patients with multiple sclerosis (MS) with frequencies observed in a healthy control Kuwaiti Arab population to relate APOE frequencies with specific identifiable clinical features of the disease.

Methods

Two groups of subjects were studied: (i) 39 (17 M, 22 F) patients with clinical evidence of MS; (ii) 106 apparently healthy Kuwaitis recruited as control subjects. The MS patients had detailed clinical and laboratory evaluations, and APOE genotypes were determined in all the subjects (patients and controls) by validated PCR methods. Differences in frequencies of APOE alleles and associations of specific alleles with clinical features were assessed.

Results

There were no significant differences in allele frequencies between patients and controls, although there was a statistically insignificant trend towards lower APOE2 allele frequency in the patients (p=0.09). There was a significant association of the APOE4 allele with female gender in the patients (p<0.05).

Conclusion

In Kuwaitis, a population with low MS prevalence, no statistically significant associations between APOE genetic polymorphism and susceptibility to MS could be established, but there was a trend towards a lower APOE2 frequency with MS and towards increased frequency of APOE4 in female patients and with severe disease.

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].

Section snippets

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).

References (20)

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