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. 2021 Summer;15(3):35-46.
doi: 10.22037/ijcn.v14i4.18795.

Association of HLA-DR2-Related Haplotype (HLA-DRB5*01-DRB1*1501-DQB1*0602) in Patients with Multiple Sclerosis in Khuzestan Province

Nooshin Delfan  1 , Hamid Galehdari  1 , Farideh Ghanbari Mardasi  1 , Rezvan Zabihi  1 , Tahereh Latifi Pakdehi  1 , Tahereh Seifi  1 , Nastaran Majdinasab  2
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Association of HLA-DR2-Related Haplotype (HLA-DRB5*01-DRB1*1501-DQB1*0602) in Patients with Multiple Sclerosis in Khuzestan Province

Nooshin Delfan et al. Iran J Child Neurol. 2021 Summer.

Abstract

Objective: Multiple sclerosis (MS) is a partially heritable autoimmune disease. HLA-DR2 is the largest identified genetic risk factor for MS. The largest identified genetic risk factor is haplotype from the MHC class II HLA-DR2, which increases the disease risk. The HLA-DR2 distribution in MS patients has been confirmed, but contradictory outcomes have been found. Moreover, the HLA-DR2 effect on ethnicity and gender is unclear. There are no data regarding the HLA-DR2 (HLA-DRB1*1501-DRB5*01-DQB1*0602) association with MS in Khuzestan Province, Iran. This study aimed to investigate the association of HLA-DR2 with MS regarding both sex and ethnicity in this province.

Materials & methods: A total of 399 individuals were recruited. HLA typing was conducted using the polymerase chain reaction amplification with sequence-specific primers technology. The HLA-DR2 association with MS was analyzed, and also its probable association with gender, ethnicity, the expanded disability status scale (EDSS), and MS clinical course was examined using the Chi-square test.

Results: HLA-DRB5*01 - -DQB1*0602 - as the most common HLA haplotype was found in both patient and control groups. In contrast, the DRB5*01 + -DRB1*1501 + -DQB1*0602 - frequency was very low in the groups. It was observed that haplotypes had no association with MS susceptibility. Most of the haplotypes showed no association with ethnicity, sex, EDSS, and MS course except for the HLA-DRB5*01 + -DRB1*1501 + -DQB1*0602 - haplotype that was positively associated with EDSS steps 5 to 10 (p=0.014) and non-RRMS (p=0.023).

Conclusion: There was no association between HLA-DR2 and MS susceptibility. However, the higher HLA-DRB5*01 + -DRB1*1501 + -DQB1*0602 - frequency may play a role in MS development. Also, HLA-DR2 did not increase significantly concerning clinical course, ethnicity, sex, and EDSS. This study further supports the importance of replication studies as susceptible loci that might differ in various ethnicities. Therefore, it is concluded that the association between HLA-DR2 and MS is more allelic than haplotypic in Khuzestan.

Keywords: HLA-DR2; HLA-DRB1*1501; Iran; Multiple sclerosis; PCR-SSP.

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Conflict of interest statement

The authors declare that they have no conflicts of interest regarding the publication of the paper.

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