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Evidence of linkage with HLA-DR in DRB1*15-negative families with multiple sclerosis.
Am J Hum Genet. 2001 Oct; 69(4):900-3.AJ

Abstract

The importance of the HLA-DR locus to multiple sclerosis (MS) susceptibility was assessed in 542 sib pairs with MS and in their families. By genotyping 1,978 individuals for HLA-DRB1 alleles, we confirmed the well-established association of MS with HLA-DRB1*15 (HLA-DRB1*1501 and HLA-DRB5*0101), by the transmission/disequilibrium test (chi2=138.3; P<.0001). We obtained significant evidence of linkage throughout the whole data set (mlod=4.09; 59.9% sharing). Surprisingly, similar sharing was also observed in 58 families in which both parents lacked the DRB1*15 allele (mlod=1.56; 62.7% sharing; P=.0081). Our findings suggest that the notion that HLA-DRB1*15 is the sole major-histocompatibility-complex determinant of susceptibility in northern-European populations with MS may be incorrect. It remains possible that the association of MS with HLA-DRB1*15 is due to linkage disequilibrium with a nearby locus and/or to the presence of disease-influencing allele(s) in DRB1*15-negative haplotypes.

Authors+Show Affiliations

Division of Neurology, Karolinska Institutet at Huddinge University Hospital, Stockholm, Sweden.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11519010

Citation

Ligers, A, et al. "Evidence of Linkage With HLA-DR in DRB1*15-negative Families With Multiple Sclerosis." American Journal of Human Genetics, vol. 69, no. 4, 2001, pp. 900-3.
Ligers A, Dyment DA, Willer CJ, et al. Evidence of linkage with HLA-DR in DRB1*15-negative families with multiple sclerosis. Am J Hum Genet. 2001;69(4):900-3.
Ligers, A., Dyment, D. A., Willer, C. J., Sadovnick, A. D., Ebers, G., Risch, N., & Hillert, J. (2001). Evidence of linkage with HLA-DR in DRB1*15-negative families with multiple sclerosis. American Journal of Human Genetics, 69(4), 900-3.
Ligers A, et al. Evidence of Linkage With HLA-DR in DRB1*15-negative Families With Multiple Sclerosis. Am J Hum Genet. 2001;69(4):900-3. PubMed PMID: 11519010.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evidence of linkage with HLA-DR in DRB1*15-negative families with multiple sclerosis. AU - Ligers,A, AU - Dyment,D A, AU - Willer,C J, AU - Sadovnick,A D, AU - Ebers,G, AU - Risch,N, AU - Hillert,J, AU - ,, Y1 - 2001/08/22/ PY - 2001/04/10/received PY - 2001/07/24/accepted PY - 2001/8/24/pubmed PY - 2001/10/19/medline PY - 2001/8/24/entrez SP - 900 EP - 3 JF - American journal of human genetics JO - Am. J. Hum. Genet. VL - 69 IS - 4 N2 - The importance of the HLA-DR locus to multiple sclerosis (MS) susceptibility was assessed in 542 sib pairs with MS and in their families. By genotyping 1,978 individuals for HLA-DRB1 alleles, we confirmed the well-established association of MS with HLA-DRB1*15 (HLA-DRB1*1501 and HLA-DRB5*0101), by the transmission/disequilibrium test (chi2=138.3; P<.0001). We obtained significant evidence of linkage throughout the whole data set (mlod=4.09; 59.9% sharing). Surprisingly, similar sharing was also observed in 58 families in which both parents lacked the DRB1*15 allele (mlod=1.56; 62.7% sharing; P=.0081). Our findings suggest that the notion that HLA-DRB1*15 is the sole major-histocompatibility-complex determinant of susceptibility in northern-European populations with MS may be incorrect. It remains possible that the association of MS with HLA-DRB1*15 is due to linkage disequilibrium with a nearby locus and/or to the presence of disease-influencing allele(s) in DRB1*15-negative haplotypes. SN - 0002-9297 UR - https://www.unboundmedicine.com/medline/citation/11519010/Evidence_of_linkage_with_HLA_DR_in_DRB1_15_negative_families_with_multiple_sclerosis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0002-9297(07)61147-1 DB - PRIME DP - Unbound Medicine ER -