PMID- 12083953
OWN - NLM
STAT- MEDLINE
DCOM- 20020718
LR  - 20191106
IS  - 1175-2203 (Print)
IS  - 1175-2203 (Linking)
VI  - 2
IP  - 1
DP  - 2002
TI  - Genetics of multiple sclerosis: linkage and association studies.
PG  - 37-58
AB  - Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central 
      nervous system caused by an interplay of environmental and genetic factors. The 
      only genetic region that has been clearly demonstrated by linkage and association 
      studies to contribute to MS genetic susceptibility is the human leukocyte antigen 
      (HLA) system. The majority of HLA population studies in MS have focused on 
      Caucasians of Northern European descent, where the predisposition to disease has 
      been consistently associated with the class II DRB1*1501-DQA1*0102-DQB1*0602 
      haplotype. A positive association with DR4 was detected in Sardinians and in 
      other Mediterranean populations. Moreover DR1, DR7, DR11 have been found to be 
      protective in several populations. Systematic searches aimed at identifying 
      non-HLA susceptibility genes were undertaken in several populations by means of 
      linkage studies with microsatellite markers distributed across the whole genome. 
      The conclusion of these studies was that there is no major MS locus, and genetic 
      susceptibility to the disease is most likely explained by the presence of 
      different genes each conferring a small contribution to the overall familial 
      aggregation. The involvement of several candidate genes was tested by association 
      studies, utilizing either a population-based (case control) or a family-based 
      (transmission disequilibrium test) approach. Candidate genes were selected mainly 
      on the basis of their involvement in the autoimmune pathogenesis and include 
      immunorelevant molecules such as cytokines, cytokine receptors, immunoglobulin, T 
      cell receptor subunits and myelin antigens. With the notable exception of HLA, 
      association studies met only modest success. This failure may result from the 
      small size of the tested samples and the small number of markers considered for 
      each gene. New tools for large scale screening are needed to identify genetic 
      determinants with a low phenotypic effect. Large collaborative studies are 
      planned to screen several thousands of patients with MS with several thousands of 
      genetic markers. The tests are increasingly based on the DNA pooling procedure.
FAU - Giordano, Mara
AU  - Giordano M
AD  - Dipartimento di Scienze Mediche, Universita del Piemonte Orientale Amedeo 
      Avogadro, Via Solaroli 17, 28100 Novara, Italy. giordano@med.unipmn.it
FAU - D'Alfonso, Sandra
AU  - D'Alfonso S
FAU - Momigliano-Richiardi, Patricia
AU  - Momigliano-Richiardi P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - New Zealand
TA  - Am J Pharmacogenomics
JT  - American journal of pharmacogenomics : genomics-related research in drug 
      development and clinical practice
JID - 100967746
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Chromosome Mapping
MH  - *Genetic Linkage
MH  - Genetic Predisposition to Disease
MH  - HLA Antigens/genetics
MH  - Humans
MH  - Multiple Sclerosis/*genetics
RF  - 165
EDAT- 2002/06/27 10:00
MHDA- 2002/07/19 10:01
CRDT- 2002/06/27 10:00
PHST- 2002/06/27 10:00 [pubmed]
PHST- 2002/07/19 10:01 [medline]
PHST- 2002/06/27 10:00 [entrez]
AID - 020104 [pii]
AID - 10.2165/00129785-200202010-00004 [doi]
PST - ppublish
SO  - Am J Pharmacogenomics. 2002;2(1):37-58. doi: 10.2165/00129785-200202010-00004.