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CORRELATION BETWEEN INTEGRIN ALPHA-4 GENE POLYMORPHISMS AND FAILURE TO RESPOND TO NATALIZUMAB THERAPY IN IRAQI MULTIPLE SCLEROSIS PATIENTS

FADIA T. AHMED 1*, SHATHA H. ALI 2, GHEYATH A AL GAWWAM 3

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Genetic variation can impact the therapeutic response of natalizumab-treated multiple sclerosis patients; accordingly, screening for gene polymorphisms of the adhesion molecule α4β1-integrin that is specifically involved in lymphocyte transmigration into the CNS and the pathogenesis of human demyelinating disease will help to identify those with a predisposition to non-response. The aim is to assess the possible association between the rs200000911 (A ˃ G,T) missense mutation at position 256 in the integrin α-4 subunit (ITGA-4) gene and the response to Natalizumab (NAT) in a sample of Iraqi patients with multiple sclerosis (MS). A sample of sixty-two patients with MS (45 females and 17 males; mean age of 31.6 years; age range of 15 to 52 years) receiving NAT for at least 12 consecutive months were involved in the study carried out from March to August 2022. The sample was categorized into two groups according to their response to NAT treatment (responders and non-responders). A polymerase chain reaction and Sanger’s sequencing of the extracted deoxyribonucleic acid were performed to identify the polymorphism at the ITGA-4 gene promoter region. The rs200000911 (A ˃ T) missense mutation was detected in both groups of patients (responders and non-responders to NAT treatment) with the absence of the rs200000911 (A ˃ G) polymorphism. Additionally, the results revealed the existence of two intronic SNPs (rs936587744 (T ˃ C) and rs2305588 (T ˃ C)). All three polymorphisms appeared to have a non-significant impact on the responsiveness to NAT, serum concentration of Vascular Cell Adhesion Molecules-1 (VCAM-1), Expanded Disability Status Scale (EDSS), or rate of relapse change through the treatment period. The rs200000911 (A ˃ T) missense mutation and the rs936587744 (T ˃ C) and rs2305588 (T ˃ C) intronic mutations are not correlated with the response to NAT in MS patients, with none of the genotypes appearing to increase the propensity to be a non-responder to NAT