Association of the HLA region with multiple sclerosis as confirmed by a genome screen using > 10,000 SNPs on DNA chips

被引:17
作者
Gödde, R
Rohde, K
Becker, C
Toliat, MR
Entz, P
Suk, A
Müller, N
Sindern, E
Haupts, M
Schimrigk, S
Nürnberg, P
Epplen, JT
机构
[1] Ruhr Univ Bochum, Dept Human Genet, D-44780 Bochum, Germany
[2] Max Delbruck Ctr Mol Med, GMC, Berlin, Germany
[3] Univ Klinikum Essen, Dept Transfus Med, Essen, Germany
[4] Ruhr Univ Bochum, Dept Neurol, Kliniken Bergmannsheil, D-4630 Bochum, Germany
[5] Ruhr Univ Bochum, Dept Neurol, Knappschaftskrankenhaus, D-4630 Bochum, Germany
[6] Ruhr Univ Bochum, St Josef Hosp, Dept Neurol, D-4630 Bochum, Germany
来源
JOURNAL OF MOLECULAR MEDICINE-JMM | 2005年 / 83卷 / 06期
关键词
D O I
10.1007/s00109-005-0650-8
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system, with a complex genetic background. Here, we present a genome screen for association in small scale, employing 11,555 single nucleotide polymorphisms (SNPs) on DNA chips for genotyping 100 MS patients stratified for HLA-DR2(+) and 100 controls. More than 500 SNPs revealed significant differences between cases and controls before Bonferroni correction. A fraction of these SNPs was reanalysed in two additional cohorts of patients and controls, using high-throughput genotyping methods. A marker on chromosome 6p21.32 (rs2395182) yielded the highest significance level, validating the established HLA-DR association.
引用
收藏
页码:486 / 494
页数:9
相关论文
共 47 条
  • [1] Genetic analysis of multiple sclerosis in Europeans:: French data
    Alizadeh, M
    Génin, E
    Babron, MC
    Birebent, B
    Cournu-Rebeix, I
    Yaouanq, J
    Dréano, S
    Sawcer, S
    Compston, A
    Clanet, M
    Edan, G
    Fontaine, B
    Clerget-Darpoux, F
    Semana, G
    [J]. JOURNAL OF NEUROIMMUNOLOGY, 2003, 143 (1-2) : 74 - 78
  • [2] HLA-DR2 dose effect on susceptibility to multiple sclerosis and influence on disease course
    Barcellos, LF
    Oksenberg, JR
    Begovich, AB
    Martin, ER
    Schmidt, S
    Vittinghoff, E
    Goodin, DS
    Pelletier, D
    Lincoln, RR
    Bucher, P
    Swerdlin, A
    Perick-Vance, MA
    Haines, JL
    Hauser, SL
    [J]. AMERICAN JOURNAL OF HUMAN GENETICS, 2003, 72 (03) : 710 - 716
  • [3] Is there a future for TNF promoter polymorphisms?
    Bayley, JP
    Ottenhoff, THM
    Verweij, CL
    [J]. GENES AND IMMUNITY, 2004, 5 (05) : 315 - 329
  • [4] HLA-DMB gene and HLA-DRA promoter region polymorphisms in Australian multiple sclerosis patients
    Bennetts, BH
    Teutsch, SM
    Buhler, MM
    Heard, RNS
    Stewart, GJ
    [J]. HUMAN IMMUNOLOGY, 1999, 60 (09) : 886 - 893
  • [5] A whole genome screen for association in Polish multiple sclerosis patients
    Bielecki, B
    Mycko, MP
    Tronczynska, E
    Bieniek, M
    Sawcer, S
    Setakis, E
    Benediktsson, K
    Compston, A
    Selmaj, KW
    [J]. JOURNAL OF NEUROIMMUNOLOGY, 2003, 143 (1-2) : 107 - 111
  • [6] Discovering genotypes underlying human phenotypes: past successes for mendelian disease, future approaches for complex disease
    Botstein, D
    Risch, N
    [J]. NATURE GENETICS, 2003, 33 (Suppl 3) : 228 - 237
  • [7] High-throughput multiplex SNP genotyping with MALDI-TOF mass spectrometry: Practice, problems and promise
    Bray, MS
    Boerwinkle, E
    Doris, PA
    [J]. HUMAN MUTATION, 2001, 17 (04) : 296 - 304
  • [8] Mapping complex disease loci in whole-genome association studies
    Carlson, CS
    Eberle, MA
    Kruglyak, L
    Nickerson, DA
    [J]. NATURE, 2004, 429 (6990) : 446 - 452
  • [9] Prognosis of multiple sclerosis: environmental factors
    I. Casetta
    E. Granieri
    [J]. Neurological Sciences, 2000, 21 (Suppl 2) : S839 - S842
  • [10] HLA typing in the United Kingdom multiple sclerosis genome screen
    Coraddu, F
    Sawcer, S
    Feakes, R
    Chataway, J
    Broadley, S
    Jones, HB
    Clayton, D
    Gray, J
    Smith, S
    Taylor, C
    Goodfellow, PN
    Compston, A
    [J]. NEUROGENETICS, 1998, 2 (01) : 24 - 33