BRIEF COMMUNICATION TCRBV20S1 polymorphism does not influence the susceptibility to type 1 diabetes and multiple sclerosis in the Sardinian population Claudio Fozza & Magdalena Zoledzieska & Maristella Pitzalis & Maria Pina Simula & Antonio Galleu & Salvatore Contini & Silvana Bonfigli & Francesco Cucca & Maurizio Longinotti Received: 28 June 2011 /Accepted: 9 September 2011 /Published online: 17 September 2011 # Springer-Verlag 2011 Abstract Among the different T-cell receptor (TCR) BV20S1 polymorphisms, nucleotide substitution at position 524 results in the introduction of a stop codon, whose potential functional relevance is still unknown. We have recently showed in Sardinian subjects the most elevated allele frequency ever reported worldwide for this “null allele” (0.44). As this variant generates a gap in the TCR repertoire, this preliminary finding prompted us to further analyze the role of this polymorphism in the susceptibility to type 1 diabetes (T1D) and multiple sclerosis (MS), which are extremely common in this popula- tion. With this aim, we evaluated the influence of the TCRBV20S1 polymorphism by assessing it with the trans- mission disequilibirum test (TDT) in 652 T1D and 616 MS families, without detecting any significant difference. We conclude that the high frequency of this null allele in Sardinia is not directly related to the high incidence of these autoimmune diseases observed in this founder population. Keywords TCRBV20S1 polymorphism . Type 1 diabetes . Multiple sclerosis . Sardinian population Common sequence variations in T-cell receptor (TCR) loci have often been considered as candidates in the modulation of the susceptibility to common immune-mediated diseases. Even though genome-wide association studies (GWAS) have failed to recognize variants in the TCR-BV (beta variable) locus influencing the risk for specific diseases (Stahl et al. 2010), three factors prompted us to evaluate the possible impact of the TCRBV20S1 “null allele“on the susceptibility to type 1 mellitus diabetes (T1D) and multiple sclerosis (MS) in the Sardinian population. First of all, the allele frequency of 0.44 for the BV20S1 “null allele“we recently detected in Sardinians (Bonfigli et al. 2007) is the most elevated reported in any ethnic group, and it is in the optimal range of frequency to detect disease association. Variants that are too rare (<5%) or too common (>95%) are difficult to detect and this might have impacted the power to detect association in previous studies. Secondly, among the three different polymorphisms de- scribed for the TCRBV20S1 gene (Charmley et al. 1993; Dresch et al. 2002), the C/T substitution at position 524 results in a stop codon (“null allele”). Therefore, 20% of Sardinians homozygous for this inactivating TCRBV single-nucleotide polymorphism (SNP) have a functional hole in their TCRBV repertoire, as BV20+ T-lymphocytes are absent in their peripheral blood. Finally, T1D and MS are determined by an immune-mediated process in which the T lymphocytes and their TCRs may have a key role and in the founder population from Sardinia they show two of the highest frequencies worldwide (Rosati et al. 1996; Songini and Muntoni 1991). Therefore, this genetic isolate represents a suitable place to investigate a possible link between the functionally relevant variants in the TCR repertoire and common immune-mediated phenotypes. To this aim, we assessed with the transmission disequi- librium test (TDT) (Spielman et al. 1993) in 652 T1D and 616 MS families if the TCRBV20S1 polymorphism, typed C. Fozza (*) : M. P. Simula : A. Galleu : S. Contini : S. Bonfigli : M. Longinotti Istituto di Ematologia, Universà di Sassari, Viale San Pietro 12, 07100 Sassari, Italy e-mail: cfozza@uniss.it M. Zoledzieska : M. Pitzalis : F. Cucca Istituto di Genetica Medica, Dipartimento di Scienze Biomediche, Università di Sassari, Sassari, Italy Immunogenetics (2012) 64:153–154 DOI 10.1007/s00251-011-0575-z