Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Variation within the CLEC16A gene shows consistent disease association with both multiple sclerosis and type 1 diabetes in Sardinia


Variation within intron 19 of the CLEC16A (KIAA0350) gene region was recently found to be unequivocally associated with type 1 diabetes (T1D) in genome-wide association (GWA) studies in Northern European populations. A variant in intron 22 that is nearly independent of the intron 19 variant showed suggestive evidence of association with multiple sclerosis (MS). Here, we genotyped the rs725613 polymorphism, representative of the earlier reported associations with T1D within CLEC16A, in 1037 T1D cases, 1498 MS cases and 1706 matched controls, all from the founder, autoimmunity-prone Sardinian population. In these Sardinian samples, allele A of rs725613 is positively associated not only with T1D (odds ratio=1.15, P one-tail=5.1 × 10−3) but also, and with a comparable effect size, with MS (odds ratio=1.21, P one-tail 6.7 × 10−5). Taken together these data provide evidence of joint disease association in T1D and MS within CLEC16A and underline a shared disease pathway.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. Marrosu MG, Cocco E, Lai M, Spinicci G, Pischedda MP, Contu P . Patients with multiple sclerosis and risk of type 1 diabetes mellitus in Sardinia, Italy: a cohort study. The Lancet 2002; 359: 1461–1465.

    Article  Google Scholar 

  2. Nielsen NM, Westergaard T, Frisch M, Rostgaard K, Wohlfahrt J, Koch-Henriksen N et al. Type 1 diabetes and multiple sclerosis: A Danish population-based cohort study. Arch Neurol 2006; 63: 1001–1004.

    Article  PubMed  Google Scholar 

  3. Marrosu MG, Motzo C, Murru R, Lampis R, Costa G, Zavattari P et al. The co-inheritance of type 1 diabetes and multiple sclerosis in Sardinia cannot be explained by genotype variation in the HLA region alone. Hum Mol Genet 2004; 13: 2919–2924.

    Article  CAS  PubMed  Google Scholar 

  4. Hakonarson H, Grant SF, Bradfield JP, Marchand L, Kim CE, Glessner JT et al. A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene. Nature 2007; 448: 591–594.

    Article  CAS  PubMed  Google Scholar 

  5. Todd JA, Walker NM, Cooper JD, Smyth DJ, Downes K, Plagnol V et al. Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes. Nat Genet 2007; 39: 857–864.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Hafler DA, Compston A, Sawcer S, Lander ES, Daly MJ, De Jager PL et al. Risk alleles for multiple sclerosis identified by a genomewide study. N Engl J Med 2007; 357: 851–862.

    Article  CAS  PubMed  Google Scholar 

  7. Thomson G . Mapping disease genes: family-based association studies. Am J Hum Genet 1995; 57: 487–498.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Lampis R, Morelli L, Congia M, Macis MD, Mulargia A, Loddo M et al. The inter-regional distribution of HLA class II haplotypes indicates the suitability of the Sardinian population for case-control association studies in complex diseases. Hum Mol Genet 2000; 12: 2959–2965.

    Article  Google Scholar 

  9. McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the international panel on the diagnosis of multiple sclerosis. Ann. Neurol 2001; 50: 121–127.

    Article  CAS  PubMed  Google Scholar 

  10. Dudbridge F . Pedigree disequilibrium tests for multilocus haplotypes. Genet Epidemiol 2003; 25: 115–121.

    Article  PubMed  Google Scholar 

  11. Spielman RS, McGinnis RE, Ewens WJ . Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM). Am J Hum Genet 1993; 52: 506–516.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Zoledziewska M, Perra C, Orru V, Moi L, Frongia P, Congia M et al. Further evidence of a primary, causal association of the PTPN22 620W variant with type 1 diabetes. Diabetes 2008; 57: 229–234.

    Article  CAS  PubMed  Google Scholar 

  13. Bottini N, Vang T, Cucca F, Mustelin T . Role of PTPN22 in type 1 diabetes and other autoimmune diseases. Semin Immunol 2006; 18: 207–213.

    Article  CAS  PubMed  Google Scholar 

  14. Vang T, Congia M, Macis MD, Musumeci L, Orru V, Zavattari P et al. Autoimmune-associated lymphoid tyrosine phosphatase is a gain-of-function variant. Nat Genet 2005; 37: 1317–1319.

    Article  CAS  PubMed  Google Scholar 

Download references


We thank Mario Maioli, Daniela Contu, Costantino Motzo, Franca Zurrida, Francesca Deidda, Gabriele Farina, Paola Cossu and Wanda Garau for help and support. This work was supported by funds from FISM-Fondazione Italiana Sclerosi Multipla—Cod. 2004/R/5to FC and from Regione Autonoma Sardegna (Progetto Educazione Sanitaria) to FC.

Author information

Authors and Affiliations


Corresponding author

Correspondence to F Cucca.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Zoledziewska, M., Costa, G., Pitzalis, M. et al. Variation within the CLEC16A gene shows consistent disease association with both multiple sclerosis and type 1 diabetes in Sardinia. Genes Immun 10, 15–17 (2009).

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:


  • type 1 diabetes
  • multiple sclerosis
  • sardinia
  • autoimmunity, CLEC16A

This article is cited by


Quick links