Cytotoxic T lymphocyte‐associated antigen‐4 gene polymorphisms confer susceptibility to atopic asthma in Korean children

Abstract

Summary. Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is a negative regulator of T lymphocyte activation. The gene encoding CTLA-4 is a candidate gene for conferring susceptibility to allergic disease. The purpose of this study was to evaluate the potential effects of CTLA-4 gene polymorphisms in Korean children on asthma. We genotyped 272 children with atopic asthma, 54 children with nonatopic asthma (NAA), and 254 control children for allelic determinants at two polymorphic sites in the region at positions promoter À318 C>T and exon 1 þ49 G>A using restriction fragment length polymorphism methods. As a result, allele and genotype frequencies of the CTLA-4 exon 1 þ49 G>A polymorphism were different to some extent between the atopic asthma children and the controls with P < 0.05, which did not reach statistical significance after the correction of multiple comparisons. In addition, CTLA-4 þ49 G>A polymorphism was significantly associated with elevated serum IgE levels (P ¼ 0.01). Of the four haplotype, haplotype 1 (C-G) was only associated with atopic asthma susceptibility after the correction of multiple comparisons

Cytotoxic T-Lymphocyte Associated Antigen 4 Polymorphisms and Asthma Risk: A Meta-Analysis

“…One article reported two cohorts [34], and each cohort was considered as a separate case-control study. Finally, a total of 18 case-control studies in 17 articles were identified [15]–[17], [25]–[38], including 6378 cases and 8674 controls. There were 11 studies on +49 A/G, 12 studies on −318 C/T, 6 studies on −1147 C/T, 5 studies on CT60 A/G, 3 studies on −1722 C/T and rs926169.…”

“…There were 10 studies of Asians [15], [17], [25]–[27], [29], [32], [34], [37], [38] and 6 studies of Caucasians [16], [28], [30], [31], [33], [36]. Five studies were performed in adults [15]–[17], [34], [38], 11 studies in children [25]–[27], [29]–[32], [34]–[37]. Two studies included both adults and juveniles [28], [33].…”

“…Five studies included only atopic asthma patients [27], [28], [34], [35], [38]. Four studies included both atopic and non-atopic asthma patients but the data for these patients could be separately extracted 17,25,26,30. Seven studies did not offer detailed information [15], [16], [29], [31]–[33], [36].…”

“…Asthma was defined with different criteria (physician's diagnosis, ATS diagnosis criteria, NHLBI/WHO guideline, NIH criteria, and Chinese asthma diagnosis criteria for children). Atopy was defined based on total IgE in 6 studies [16], [17], [25], [27], [28], [32], radioallergosorbent test (RAST) in 2 studies [15], [27], skin prick test to common aeroallergens (SPT) in 9 studies [16], [17], [25], [26], [28], [30], [33], [34], [38], and allergen-specific IgE in 4 studies [26], [29], [30], [37]. The quality scores ranged from 5 to 12, suggesting high quality.…”

Interaction of T-cell and antigen presenting cell co-stimulatory genes in childhood IgE

“…CD86 [3], CD40 [4], CTLA4 [5,26], HLA-G [6], ICOS [7] and PDCD1 [8], yet other genes were found not to be associated with atopy such as CD28 [5] and LILRB4 [27]. A summary of these association studies is presented in table E4 of the supplementary material.…”