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A high density SNP genotyping approach within the 19q13 chromosome region identifies an association of a CNOT3 polymorphism with ankylosing spondylitis
  1. Roberto Díaz-Peña1,
  2. Ana M Aransay2,
  3. Beatriz Suárez-Álvarez1,
  4. Jacome Bruges-Armas3,
  5. Naiara Rodríguez-Ezpeleta2,
  6. María Regueiro2,4,
  7. Fernando M Pimentel-Santos5,6,
  8. Juan Mulero7,
  9. Alejandra Sánchez7,
  10. Eduardo Collantes8,
  11. Rubén Queiro9,
  12. Javier Ballina9,
  13. Helena Alves10,
  14. Carlos López-Larrea1
  1. 1Department of Immunology, Hospital Universitario Central de Asturias, Oviedo, Spain
  2. 2Genome Analysis Platform, Functional Genomics Unit, CIC bioGUNE, Bizkaia Technology Park, Derio, Spain
  3. 3Institute for Molecular and Cell Biology, University of Porto, Porto, Portugal
  4. 4Department of Molecular and Human Genetics, College of Medicine, Florida International University, Miami, Florida, USA
  5. 5CEDOC, Faculdade de Ciências Médicas da Universidade Nova de Lisboa, Lisboa, Portugal
  6. 6CHLO, Department of Rheumatology, Hospital de Egas Moniz, Lisboa, Portugal
  7. 7Department of Rheumatology, H U Puerta de Hierro, Madrid, Spain
  8. 8Hospital Universitario “Reina Sofía”, IMIBIC, Universidad de Córdoba, Córdoba, Spain
  9. 9Rheumatology Department, Hospital Universitario Central de Asturias, Oviedo, Spain
  10. 10Centro de Histocompatibilidade do Norte, Porto, Portugal
  1. Correspondence to Carlos López Larrea, Department of Immunology, Hospital Universitario Central de Asturias, C/ Celestino Villamil s/n, 33006-Oviedo, Spain; inmuno{at}


Objective To identify genomic variants in the 19q13 chromosome region associated with ankylosing spondylitis (AS) in human leucocyte antigen (HLA)-B27-positive populations.

Methods High-throughput genotyping of 1536 haplotype-tag single nucleotide polymorphisms (SNPs) was performed in 249 patients with AS and 302 healthy controls. Some of the identified associations were validated by genotyping four SNPs in two additional cohorts consisting of 412 cases/301 controls and 144 cases/203 controls. All individuals selected (both cases and controls) were HLA-B27-positive.

Results Two markers in two different genes (CNOT3 and LAIR2) showed significant association (p<10−3) with AS. In addition, sliding windows analysis showed association of groups of adjacent SNPs in regions located around CNOT3 (Chr19: 59347459-59356564, p=2.43×10−4 to 6.54×10−4). The associations were validated by genotyping four SNPs from regions located near LAIR2 and CNOT3 genes (rs1055234, rs8111398, rs2287828 and rs4591276) in two additional cohorts. The CNOT3 polymorphism (rs1055234) remained associated with AS (combined p=9.73×10−6). One SNP, located downstream of KIR3DL1, was detected which, tested in combination with HLA-Bw4I80, was associated with AS.

Conclusion A novel significant association was detected between SNP rs1055234 and AS susceptibility.

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  • Competing interests None.

  • Funding This work was supported by FIS 08/0566, FICYT PC10-70 and ETORTEK/2005–2010 grants.

  • Ethics approval Hospital Universitario Central de Asturias.

  • Provenance and peer review Not commissioned; externally peer reviewed.