Cytotoxic T-Lymphocyte-Associated Antigen 4 Gene Polymorphisms in Japanese Children with Infection-Associated Hemophagocytic Lymphohistiocytosis

Objective: This study examined whether genetic polymorphisms in cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), a negative regulator of T cells, are associated with infection-associated hemophagocytic lymphohistiocytosis (IHLH) in Japanese children. Methods: We investigated the alleles of four polymorphisms in the CTLA-4 gene [-318CT, +49AG, CT60 and a dinucleotide repeat length polymorphism (AT)n] in 43 Japanese children with IHLH and 100 healthy Japanese controls. The hyper-polymorphic (AT) n alleles were divided into two types; the shortest allele (designated as AT(7)) and the longer alleles (designated as AT(>7)). Results: A significant difference in the distribution of the (AT) n genotype was found between patients and controls (p = 0.028). Also, the frequency of the AT(>7) allele was significantly higher in the patients with IHLH than in the controls (p = 0.007). No significant linkage disequilibrium was found between each polymorphism. With regard to laboratory data, patients homozygous for the CTLA-4 AT(>7) allele showed significantly higher serum levels of lactate dehydrogenase and soluble interleukin-2 receptor than patients with the other alleles. Conclusion: These results suggest that CTLA-4 polymorphisms might play a role in the development of IHLH in Japanese children. Copyright (C) 2010 S. Karger AG, Basel