DNA length polymorphism of tetranucleotide repeat at the 5′ side of the myelin basic protein gene in Russian multiple sclerosis patients

T. V. Andreewski, F. R. Guerini, M. A. Sudomoina, A. N. Boiko, A. D. Alekseenkov, O. G. Kulakova, L. Losciale, P. Ferrante, E. I. Gusev, O. O. Favorova

Research output: Contribution to journalArticle

Abstract

The myelin basic protein gene (MBP) can confer the susceptibility to multiple sclerosis, because its protein product is the main protein component of myelin of the central nervous system and a potential autoimmune antigen in the disease. A possible association of multiple sclerosis with alleles and genotypes of a microsatellite repeat (TGGA)n, located to the 5′ side from the first exon of MBP in ethnic Russians (126 patients with definite multiple sclerosis and 142 healthy controls from Central Russia) was analyzed in a case-control study. Upon separation of the tetranucleotide repeat amplification products in 1.5% agarose gel, one can see two distinct bands that can be analyzed as two allele groups (A and B). The distribution of allele A and B group frequencies as well as phenotype frequency of alleles B and genotype frequency of A/A differs significantly in multiple sclerosis patients and healthy controls. Alleles A and genotype A/A are associated with multiple sclerosis. We also analyzed the association of multiple sclerosis with combined bearing of alleles and genotypes A and B of MBP and groups of alleles of the DRB1 gene of the major histocompatibility complex that correspond to serological specificities DR1-DR18. The comparison of subgroups of multiple sclerosis patients and healthy individuals, stratified according to HLA-DRB1 phenotypes, has shown a reliable increase in the phenotype frequency of allele B in healthy individuals and the genotype A/A frequency in patients, only among DR4- and DR5-positive individuals. No significant difference was found in the MBP allele and genotype distribution between multiple sclerosis patients and healthy individuals in combined groups of (DR4,DR5)-negative individuals, i.e., in the group of carriers of any phenotype except DR4 and DR5. Thus, MBP or some other nearby gene is involved in the multiple sclerosis development in Russians, predominantly (or exclusively) among DR4 and DR5 carriers. In this case, without stratification of analyzed individuals by the MBP alleles, multiple sclerosis is associated only with DR2(15), but not DR4 and DR5 alleles of DRB1. The results obtained are in favor of the genetic heterogeneity of multiple sclerosis, and suggest the possibility of epistatic interactions between the MBP and DRB1 genes.

Original languageEnglish
Pages (from-to)849-855
Number of pages7
JournalMolecular Biology
Volume37
Issue number6
DOIs
Publication statusPublished - Nov 2003

Fingerprint

Myelin Basic Protein
Microsatellite Repeats
Multiple Sclerosis
Alleles
DNA
Genes
Genotype
Phenotype
Gene Frequency
Myelin Proteins
HLA-DRB1 Chains
Genetic Heterogeneity
Russia
Major Histocompatibility Complex
Sepharose
Case-Control Studies
Exons
Central Nervous System
Gels

Keywords

  • Allele polymorphism
  • DNA
  • DRB1 gene
  • Functional genomics
  • Genotyping
  • Major histocompatibility complex
  • Man
  • Microsatellite repeat
  • Multiple sclerosis
  • Myelin basic protein gene
  • Polymerase chain reaction

ASJC Scopus subject areas

  • Genetics

Cite this

DNA length polymorphism of tetranucleotide repeat at the 5′ side of the myelin basic protein gene in Russian multiple sclerosis patients. / Andreewski, T. V.; Guerini, F. R.; Sudomoina, M. A.; Boiko, A. N.; Alekseenkov, A. D.; Kulakova, O. G.; Losciale, L.; Ferrante, P.; Gusev, E. I.; Favorova, O. O.

In: Molecular Biology, Vol. 37, No. 6, 11.2003, p. 849-855.

Research output: Contribution to journalArticle

Andreewski, TV, Guerini, FR, Sudomoina, MA, Boiko, AN, Alekseenkov, AD, Kulakova, OG, Losciale, L, Ferrante, P, Gusev, EI & Favorova, OO 2003, 'DNA length polymorphism of tetranucleotide repeat at the 5′ side of the myelin basic protein gene in Russian multiple sclerosis patients', Molecular Biology, vol. 37, no. 6, pp. 849-855. https://doi.org/10.1023/B:MBIL.0000008353.74758.c7
Andreewski, T. V. ; Guerini, F. R. ; Sudomoina, M. A. ; Boiko, A. N. ; Alekseenkov, A. D. ; Kulakova, O. G. ; Losciale, L. ; Ferrante, P. ; Gusev, E. I. ; Favorova, O. O. / DNA length polymorphism of tetranucleotide repeat at the 5′ side of the myelin basic protein gene in Russian multiple sclerosis patients. In: Molecular Biology. 2003 ; Vol. 37, No. 6. pp. 849-855.
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T1 - DNA length polymorphism of tetranucleotide repeat at the 5′ side of the myelin basic protein gene in Russian multiple sclerosis patients

AU - Andreewski, T. V.

AU - Guerini, F. R.

AU - Sudomoina, M. A.

AU - Boiko, A. N.

AU - Alekseenkov, A. D.

AU - Kulakova, O. G.

AU - Losciale, L.

AU - Ferrante, P.

AU - Gusev, E. I.

AU - Favorova, O. O.

PY - 2003/11

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N2 - The myelin basic protein gene (MBP) can confer the susceptibility to multiple sclerosis, because its protein product is the main protein component of myelin of the central nervous system and a potential autoimmune antigen in the disease. A possible association of multiple sclerosis with alleles and genotypes of a microsatellite repeat (TGGA)n, located to the 5′ side from the first exon of MBP in ethnic Russians (126 patients with definite multiple sclerosis and 142 healthy controls from Central Russia) was analyzed in a case-control study. Upon separation of the tetranucleotide repeat amplification products in 1.5% agarose gel, one can see two distinct bands that can be analyzed as two allele groups (A and B). The distribution of allele A and B group frequencies as well as phenotype frequency of alleles B and genotype frequency of A/A differs significantly in multiple sclerosis patients and healthy controls. Alleles A and genotype A/A are associated with multiple sclerosis. We also analyzed the association of multiple sclerosis with combined bearing of alleles and genotypes A and B of MBP and groups of alleles of the DRB1 gene of the major histocompatibility complex that correspond to serological specificities DR1-DR18. The comparison of subgroups of multiple sclerosis patients and healthy individuals, stratified according to HLA-DRB1 phenotypes, has shown a reliable increase in the phenotype frequency of allele B in healthy individuals and the genotype A/A frequency in patients, only among DR4- and DR5-positive individuals. No significant difference was found in the MBP allele and genotype distribution between multiple sclerosis patients and healthy individuals in combined groups of (DR4,DR5)-negative individuals, i.e., in the group of carriers of any phenotype except DR4 and DR5. Thus, MBP or some other nearby gene is involved in the multiple sclerosis development in Russians, predominantly (or exclusively) among DR4 and DR5 carriers. In this case, without stratification of analyzed individuals by the MBP alleles, multiple sclerosis is associated only with DR2(15), but not DR4 and DR5 alleles of DRB1. The results obtained are in favor of the genetic heterogeneity of multiple sclerosis, and suggest the possibility of epistatic interactions between the MBP and DRB1 genes.

AB - The myelin basic protein gene (MBP) can confer the susceptibility to multiple sclerosis, because its protein product is the main protein component of myelin of the central nervous system and a potential autoimmune antigen in the disease. A possible association of multiple sclerosis with alleles and genotypes of a microsatellite repeat (TGGA)n, located to the 5′ side from the first exon of MBP in ethnic Russians (126 patients with definite multiple sclerosis and 142 healthy controls from Central Russia) was analyzed in a case-control study. Upon separation of the tetranucleotide repeat amplification products in 1.5% agarose gel, one can see two distinct bands that can be analyzed as two allele groups (A and B). The distribution of allele A and B group frequencies as well as phenotype frequency of alleles B and genotype frequency of A/A differs significantly in multiple sclerosis patients and healthy controls. Alleles A and genotype A/A are associated with multiple sclerosis. We also analyzed the association of multiple sclerosis with combined bearing of alleles and genotypes A and B of MBP and groups of alleles of the DRB1 gene of the major histocompatibility complex that correspond to serological specificities DR1-DR18. The comparison of subgroups of multiple sclerosis patients and healthy individuals, stratified according to HLA-DRB1 phenotypes, has shown a reliable increase in the phenotype frequency of allele B in healthy individuals and the genotype A/A frequency in patients, only among DR4- and DR5-positive individuals. No significant difference was found in the MBP allele and genotype distribution between multiple sclerosis patients and healthy individuals in combined groups of (DR4,DR5)-negative individuals, i.e., in the group of carriers of any phenotype except DR4 and DR5. Thus, MBP or some other nearby gene is involved in the multiple sclerosis development in Russians, predominantly (or exclusively) among DR4 and DR5 carriers. In this case, without stratification of analyzed individuals by the MBP alleles, multiple sclerosis is associated only with DR2(15), but not DR4 and DR5 alleles of DRB1. The results obtained are in favor of the genetic heterogeneity of multiple sclerosis, and suggest the possibility of epistatic interactions between the MBP and DRB1 genes.

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KW - DNA

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KW - Functional genomics

KW - Genotyping

KW - Major histocompatibility complex

KW - Man

KW - Microsatellite repeat

KW - Multiple sclerosis

KW - Myelin basic protein gene

KW - Polymerase chain reaction

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