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.


CONCLUSIONS
These results suggest that CTLA-4 polymorphisms might play a role in the development of IHLH in Japanese children.
Department of Pediatrics, Wakayama Medical University, Wakayama, Japan.
Megumi
M
Yoshiyama
Shinji
S
Kounami
Keiko
K
Nakayama
Takahiro
T
Okutani
Noriyuki
N
Aoyagi
Norishige
N
Yoshikawa
D000293:Adolescent; D000483:Alleles; D015703:Antigens, CD / Q000235:genetics*; D060908:CTLA-4 Antigen; D002648:Child; D002675:Child, Preschool; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007223:Infant; D007239:Infections / Q000150:complications* / Q000382:microbiology / Q000821:virology; D007564:Japan; D045022:Lactate Dehydrogenases / Q000097:blood; D051359:Lymphohistiocytosis, Hemophagocytic / Q000097:blood / Q000150:complications / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic; D015375:Receptors, Interleukin-2 / Q000097:blood; D013223:Statistics as Topic
D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D015375:Receptors, Interleukin-2; D045022:Lactate Dehydrogenases