GP6 rs2304166 polymorphism is associated with response to natalizumab in multiple sclerosis patients

AlMojel, Malak; Alroughani, Raed; Kannankeril, Texy; Dashti, Mohammed; Al-Temaimi, Rabeah

doi:10.1186/s40893-019-0039-0

Cited by 4 publications

(4 citation statements)

References 24 publications

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“…Recently, a study has established to identify pharmacogenetic factor(s) associated with MS patients' response to NTZ (Tysabri), which found that the variant (rs2304166) in GP6 gene is associated with poor response to NTZ (Tysabri) in homozygous CC genotype MS patients. Al-Mojel et al (2019) investigated the possible inference of genes encoding detoxification enzyme GSTP1 and NQO1 polymorphisms on NTZ (Tysabri) response in MS, this study concluded a significantly increased frequency of double NQO1 an2d GSTP1 mutant polymorphisms in nonresponders compared to the responders (23) . In conclusion, VLA-4 polymorphisms at the level of SNP at positions 269 (C/A) have no role in MS susceptibility or NTZ responsiveness.…”

Section: A B Figure 1 Pcr Products Of Vla-4 Gen; A: a Allele In Patie...mentioning

confidence: 98%

The Impact of Very Late Antigen 4 Polymorphism on Drug Responsiveness in Patients With Multiple Sclerosis Initiation

Khaliel¹,

Abbas²,

Hatem³

et al. 2022

IraqiJMS

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Background: Very late antigen 4 (VLA4) integrin facilitates the immune cells migration to central nervous system (CNS) through blood brain barrier (BBB), so the polymorphism in this gene may be considered as genetic risk factor for multiple sclerosis (MS) occurrence. It may interact with the responsiveness level of Natalizumab. Objective: To show if VLA4 single nucleotide gene polymorphism (SNP) (C-269-A) considered as genetic predisposition factor for MS and if have a role in Natalizumab (Tysabri) drug non-responsiveness. Methods: Sixty-six (66) person with MS and 60 healthy persons involved in this study, their ages were range from 14 to 67 years. They attended to seek treatment in the MS outpatient’s clinic, at Baghdad Teaching Hospital, Medical City Complex from December 2018 to March 2020. Patient were divided into two group; resistant group (34) and response group (32). The VLA-4 SNP polymorphism investigated by sequence specific primer polymerase chain reaction (SSP-PCR) technique. Results: The VLA4 gene SSP-PCR genotyping revealed no significant differences between patients and control group also between responder patients and non-responder to Natalizumab. Conclusion: VLA-4 polymorphisms at the level of SNP at positions 269 (C/A) have no role in MS susceptibility or Natalizumab responsiveness. Keywords: MS, Natalizumab, VLA-4 Citation: Khaliel AH, Abbas AA, Hatem AO, Abdulamir AS. The impact of Very Late Antigen 4 polymorphism on drug responsiveness in patients with multiple sclerosis initiation. Iraqi JMS. 2022; 20(1): 83-89. doi: 10.22578/IJMS.20.1.11

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Section: A B Figure 1 Pcr Products Of Vla-4 Gen; A: a Allele In Patie...mentioning

confidence: 98%

The Impact of Very Late Antigen 4 Polymorphism on Drug Responsiveness in Patients With Multiple Sclerosis Initiation

Khaliel¹,

Abbas²,

Hatem³

et al. 2022

IraqiJMS

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“…The responsiveness of NAT-treated patients was determined by the presence of a steady or decreased EDSS and relapse absence. In contrast, NAT-unresponsive MS patients were diagnosed on the basis of an elevated EDSS despite treatment and the occurrence of relapses during the course of therapy [24,25]. Furthermore, the development of anti-NAT neutralizing antibodies was investigated by a specific ELISA kit to exclude antibody-positive patients from the NATunresponsive group.…”

Section: Groups Of Patients and Clinical Assessmentmentioning

confidence: 99%

Correlation Between Integrin Alpha-4 Gene Polymorphisms and Failure to Respond to Natalizumab Therapy in Iraqi Multiple Sclerosis Patients

Ahmed¹

2023

FARMACIA

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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. 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...

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“…In contrast, NAT-unresponsive MS patients were diagnosed on the basis of an elevated EDSS despite treatment alone or combined with the occurrence of relapses during the course of therapy. 28,29 The development of anti-NAT neutralizing antibodies was investigated by a specific ELISA kit to exclude antibody positive patients from the NAT unresponsive group. Four patients from group B were NAT antibody positive and they were excluded from the study.…”

Section: Patients' Groups and Clinical Assessmentmentioning

confidence: 99%

Integrin alpha-4 gene polymorphism in relation to natalizumab response in multiple sclerosis patients

Ahmed¹,

Ali²,

AlGawwam³

2023

NeuroAsia

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Objectives: The aim of this study was to assess the possible the association between +3061 (G>A, rs1143676) missense mutation in exon 24 of the integrin α-4 subunit (ITGA-4) gene and the response to natalizumab in a sample of Iraqi multiple sclerosis patients. Methods: A sample of 59 patients with multiple sclerosis (16 males and 43 females; mean age of 32 years; age range of 15 to 52 years) receiving natalizumab for at least 12 consecutive months were involved in the study between March and August/ 2022. The sample was categorized into two groups according to their response to natalizumab treatment (responders and non-responders). Polymerase chain reaction and Sanger’s sequencing for the extracted deoxyribonucleic acid was performed to identify the polymorphism at ITGA-4 gene promoter region. Results: The 3061 AA and AG genotypes were present in both groups (responders and non-responders to natalizumab treatment) with the lack of the wild form GG genotype. The AG genotype was significantly present in the non-responders’ group and appeared to have a significant impact on the responsiveness to natalizumab by increasing the propensity of being non-responder with a positive correlation (Phi-coefficient of 0.294) on the contrary of AA genotype. Conclusion: The +3061 (G.A) missense mutation is related to the response to natalizumab in multiple sclerosis patients with the AG genotype, thereby increasing the likelihood of non-response significantly.

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GP6 rs2304166 polymorphism is associated with response to natalizumab in multiple sclerosis patients

Cited by 4 publications

References 24 publications

The Impact of Very Late Antigen 4 Polymorphism on Drug Responsiveness in Patients With Multiple Sclerosis Initiation

The Impact of Very Late Antigen 4 Polymorphism on Drug Responsiveness in Patients With Multiple Sclerosis Initiation

Correlation Between Integrin Alpha-4 Gene Polymorphisms and Failure to Respond to Natalizumab Therapy in Iraqi Multiple Sclerosis Patients

Integrin alpha-4 gene polymorphism in relation to natalizumab response in multiple sclerosis patients

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