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The genetics of multiple sclerosis. A review
1Department of Neurology, MCP-Hahnemann University, Philadelphia, PA 19102, USA.
Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|November 11, 1999
Summary
Genetic factors contribute to multiple sclerosis (MS) susceptibility, with the major histocompatibility complex (MHC) being a key area of investigation. While multiple genes likely influence MS risk, the MHC region shows the most consistent association with the disease.
Area of Science:
- Neuroimmunology
- Genetics
- Epidemiology
Background:
- Multiple sclerosis (MS) is a chronic central nervous system inflammatory and demyelinating disease with unknown etiology.
- Epidemiological studies suggest both genetic and environmental factors contribute to MS pathogenesis.
- Family and twin studies indicate a significant inheritable component to MS susceptibility.
Purpose of the Study:
- To investigate genetic associations with MS susceptibility.
- To identify specific genes and chromosomal regions linked to MS.
- To explore the genetic architecture of MS, differentiating between familial and sporadic forms.
Main Methods:
- Case-control studies examining associations with polymorphic alleles of candidate genes.
- Genome-wide scans in multiplex families to identify susceptibility loci.
- Analysis of major histocompatibility complex (MHC) and human leukocyte antigen (HLA) associations.
- Segregation analysis in families with multiple affected members.
Main Results:
- A consistent association was found with the major histocompatibility complex (MHC) human leukocyte antigen (HLA) class II, DR15, DQ6, Dw2 haplotype.
- Genomic scans confirmed linkage of multiple loci with minor contributions to MS susceptibility, notably at 6p21 (MHC complex).
- MHC linkage was specifically associated with families segregating HLA DR2 alleles, suggesting a shared susceptibility marker between sporadic and familial MS.
Conclusions:
- MS is a complex genetic trait with small contributions from individual genes.
- The MHC region, particularly HLA DR2, plays a significant role in MS susceptibility.
- Further research with larger family sets and more polymorphic markers is needed to identify additional MS susceptibility loci and elucidate pathogenic mechanisms.