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.
RezumatVariația genică poate influența răspunsul terapeutic al pacienților cu scleroză multiplă tratați cu natalizumab. Decelarea polimorfismului genetic al α4β1-integrina contribuie la identificarea genelor rezistente la terapie. Scopul acestui studiu a fost evaluarea asocierii între mutația rs200000911 (A ˃ G, T) în poziția 256 a genei integrinei α-4 (ITGA-4) și răspunsul la natalizumab (NAT) într-un eșantion de pacienți irakieni cu scleroză multiplă (SM). În studiu au fost incluși 62 de pacienți cu SM care au primit NAT timp de cel puțin 12 luni consecutive în perioada martie-august 2022. Lotul a fost împărțit în două grupuri în funcție de răspunsul lor la tratamentul cu NAT (respondenți și non-respondenți). S-au efectuat polimerizarea și secvențierea Sanger a ADN-ului extras de la subiecți pentru a identifica polimorfismul genei ITGA-4. Mutația missense rs200000911 (A ˃ T) a fost detectată în ambele grupuri de pacienți, cu absența polimorfismului rs200000911 (A ˃ G). Toate cele trei forme polimorfe nu au avut un impact semnificativ asupra reactivității la N...