HLA-DRB1 differences in allelic distribution between familial and sporadic multiple sclerosis in a Hellenic cohort

ABSTRACT

Objective: Familial Multiple Sclerosis (fMS) is reported to have distinct clinical and imaging characteristics in comparison to the sporadic disease (sMS). Nevertheless, the genetic/immunogenetic profile of fMS has never been investigated in depth, so far. In this study, we examined differences of HLA-DRB1 allelic frequencies between 57 fMS and 141 sMS Hellenic patients, with reference to 246 previously genotyped healthy controls (HCs).

Patients and Methods: All patients underwent medical interview and DRB1 genotyping, using a low-resolution SSOP technique. Statistical analyses were performed using SPSS v.21.0 software, with significance set at 0.05, and p value corrected according to the Benjamini–Yekutieli method.

Results: 29 fMS cases had at least one 1^st degree relative affected (fMS 1^st), while the rest had at least one 2^nd or 3^rd degree relative affected (fMS 2^nd/3^rd). Parent-of-origin effects were observed, with the prevalence of maternal inheritance. Frequency of DRB1*15 was significantly increased in fMS and sMS, in comparison to HCs (p = 0.002 and <0.001, respectively). After fMS stratification, this result was mainly attributed to the fMS 2^nd/3^rd subgroup. DRB1*11 frequency was significantly decreased only in sMS (p < 0.001) with fMS approximating HCs’ frequency, especially for the fMS 1^st subgroup. Heterozygosity was favored over homozygosity in all groups.

Conclusion: We propose possible HLA-DRB1 allelic distribution differences between fMS and sMS, which become more apparent as proximity of affected relative/-es in fMS increases, supporting a rather degraded role of DRB1 alleles in fMS HLA/immunogenetics and indicating the concomitant implication of other HLA and non-HLA polymorphisms.

KEYWORDS:

• Multiple sclerosis
• human leucocyte antigens
• HLA-DRB1
• immunogenetics
• familial
• hellenic population

Acknowledgments

The authors would like to thank all patients who helped for the realization of this study.

Declaration of interest

The authors declare no conflicts of interest in relevance with the present study.

Declaration of financial/other relationships

Authors and peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded by the National and Kapodistrian University of Athens.