Possible Association of Cytotoxic T Lymphocyte Antigen-4 Genetic Polymorphism With Liver Damage of Primary Biliary Cirrhosis in Japan

Abstract

Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an important inhibitor of T -lymphocyte response. Polymorphisms in the CTLA-4 gene have been reported to be associated with numerous autoimmune diseases. The aim of this study was to determine whether polymorphisms of CTLA-4 exon 1 (+49) genes are associated with susceptibility and clinicolaboratory findings of primary biliary cirrhosis (PBC) in the J apanease population. Blood samples were obtained from 45 patients (6 men and 39 women, aged 23-56 years) with PBC and 73 healthy controls (48 men and 25 women, aged 22-72 years). CTLA-4 ex on 1 (+49) polymorphism was defined using a polymerase chain reaction-restriction fragment length polymorphism with Bst71I restriction enzyme. The genotype frequencies of AI A, A/G, and GIG in 45 patients with PBC were 11% (5 patients), 44% (20 patients), and 44% (20 patients), respectively. There was no significant difference between frequencies in PBC patients and healthy controls. PBC patients with GIG genotype had significantly higher serum levels of ALT, GGT, and IgM than those in patients with AI A or A/G genotype. In conclusion, CTLA -4 gene polymorphisms are not associated with susceptibility of PBC in Japan; however, GIG genotype may be associated with liver damage.

Association analysis of cytotoxic T-lymphocyte antigen 4 gene polymorphisms with primary biliary cirrhosis in Japanese patients

“…Our finding corroborated a previous report [31], in which 49AG was not associated with susceptibility to PBC but there was a discrepancy in association with liver damage that might have arisen from the number of cases analyzed.…”

“…Although early studies found an association between SNP 49G coding and PBC [22][23][24], ensuing reports showed negative relationships with susceptibility [25][26][27][28][29][30] or a positive association with liver damage [31]. A recent investigation reported that rs231725 in the 3'…”

Polymorphisms in CTLA4 Influence Incidence of Drug-Induced Liver Injury after Renal Transplantation in Chinese Recipients

“…The association between CTLA4 SNPs and liver damage has been studied in two papers. Kanno et al [17] identified that the CTLA4 +49 (rs231775) genotype was positively associated with liver damage in primary biliary cirrhosis (PBC) in Japanese populations and that PBC patients with the G/G genotype had significantly higher serum levels of ALT, GGT, and IgM than did patients with the A/A or A/G genotype. Valenti et al [18] observed a significantly higher prevalence of the susceptible CTLA4 allele (both in the heterozygous [OR 2.5] and in the homozygous [OR 4.6] state) in patients with alcoholic liver disease (ALD) compared to healthy subjects; this relationship was independent of age, sex and geographical origin.…”

“…Kanno et al [17] discovered that SNP CTLA4 +49GG (rs231775) may be associated with the liver damage of primary biliary cirrhosis (PBC) in Japanese populations. Valenti et al [18] observed a significantly higher prevalence of subjects carrying the CTLA4 susceptibility allele (both in the heterozygous and homozygous states) among patients with ALD compared to healthy subjects.…”

Duplication of MER115 on chromosome 4 in patients with primary biliary cirrhosis

“…Additional regions within the major histocompatibility complex have also been linked with PBC and the combination of the complement component C4 null allele and DRB1 Ã 08 provides a 180-fold increased relative risk for disease (6). Other genetic correlations with PBC patients include the vitamin D receptor (8)(9)(10)(11), cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) (12)(13)(14)(15)(16), natural resistance-associated macrophage protein 1 (17), tumour necrosis factor-a promoter (18), the mannosebinding lectin gene (19) and interleuklin-1 gene (5). Apart from DRB1 Ã 08, these associations have not been consistently confirmed although CTLA-4 may be associated with PBC in specific populations (12)(13)(14)(15)(16).…”