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Role of predisposing and protective HLA-DQA and HLA-DQB alleles in Sardinian multiple sclerosis
M G Marrosu1, F Muntoni, M R Murru
1Institute of Child Neurology and Psychiatry, University of Cagliari, Italy.
Objective:
To study the role of HLA genes in susceptibility and resistance to multiple sclerosis (MS) in Sardinian patients. To verify whether HLA-DQA and HLA-DQB genes differed between unrelated (MSU) and related (MSR) patients, and whether relapsing-remitting and chronic progressive forms of MS are immunogenetically distinct entities.
Design:
Case-control study of HLA-DQA and HLA-DQB gene frequency.
Setting:
All patients investigated were followed up by our MS referral centers.
Patients:
The study involved 116 MSU patients, 67 of whom had a relapsing-remitting form (MSr), 28 of whom had a chronic progressive from-the-onset form (MSc), and 21 of whom had a benign form (MSb), 32 patients with MSR, 19 parents and 27 healthy siblings of patients with MSR, and 86 controls. Selection of patients was random, while control subjects came from families without known immunologic diseases. All patients had definite MS.
Main Outcome Measure:
Statistical analysis of gene frequencies was conducted with the chi 2 test with correction (Pc) for the alleles investigated, as was decided before the study began.
Results:
The DQA1*0301 allele was found to be increased in patients (MSU vs controls, Pc = .008; patients with MSc vs controls, Pc = .001; patients with MSR vs controls, Pc = .02; and parents vs controls, Pc = .04), while the DQA1*0102 allele was found to be diminished in patients with MSr vs controls (Pc = .001). Among the DQB genes, the DQB1*0502 allele was diminished in patients with MSr vs controls (Pc = .04), while the sum of DQB1*0201 and *0302 alleles was significantly increased in patients with MSR vs controls (Pc = .003).
Conclusion:
Both HLA-DQA and HLA-DQB genes influence genetic susceptibility and resistance to MS. The roles of these genes differ in the various forms of MS. Patients with MSU and MSR both share HLA-DQA susceptibility genes.
Insights
Human Leukocyte Antigen (HLA) genes play a role in multiple sclerosis (MS) susceptibility and resistance. Specific HLA-DQA and HLA-DQB alleles are associated with different MS forms and patient groups in Sardinia.
Area of Science:
- Immunogenetics
- Human genetics
- Neurology
Background:
- Multiple Sclerosis (MS) is a complex neurological disorder with a significant genetic component.
- Human Leukocyte Antigen (HLA) genes are known to be involved in immune system regulation and disease susceptibility.
- Previous studies suggest a link between specific HLA alleles and MS risk, but the role in distinct MS subtypes and familial versus sporadic cases requires further investigation.
Purpose of the Study:
- To investigate the association of HLA-DQA and HLA-DQB genes with susceptibility and resistance to Multiple Sclerosis (MS) in the Sardinian population.
- To determine if HLA-DQA and HLA-DQB gene frequencies differ between unrelated (MSU) and related (MSR) MS patients.
- To explore potential immunogenetic distinctions between relapsing-remitting and chronic progressive forms of MS.
Main Methods:
- A case-control study design was employed to analyze HLA-DQA and HLA-DQB gene frequencies.
- The study included 116 unrelated MS patients (MSU), 32 related MS patients (MSR), their relatives (19 parents, 27 siblings), and 86 healthy controls.
- Statistical analysis utilized the chi-squared test with correction (Pc) for allele frequency comparisons.
Main Results:
- The DQA1*0301 allele was significantly increased in various MS patient groups (MSU, MSc, MSR) and their parents compared to controls.
- The DQA1*0102 allele was diminished in relapsing-remitting MS (MSr) patients compared to controls.
- Specific DQB genes showed differential associations: DQB1*0502 was diminished in MSr patients, while DQB1*0201 and *0302 combined were increased in MSR patients.
Conclusions:
- Both HLA-DQA and HLA-DQB genes contribute to genetic susceptibility and resistance to Multiple Sclerosis.
- The influence of these HLA genes varies across different forms of MS.
- Unrelated (MSU) and related (MSR) MS patients share common HLA-DQA susceptibility genes.