The distributions of genotypes in 37 children with cITP are presented in Table I. Strong associations with ITP were observed at four loci, namely, FCGR3A, FCGR3B, TNF and LTA. Of these, the FCGR3B locus is particularly interesting (P = 0·0034) because of the over-representation of the NA1 allele, which is associated with more robust binding of IgG compared with the NA2 allele (Salmon et al, 1990; Nagarajan et al, 1995). The NA1/NA1 genotype was observed in 30% of patients compared with 10% of controls (P = 0·0022(f), OR = 3·91; 95% CI: 1·51–9·61). In addition, a second low-affinity FcγR, FCGR3A, was informative in our analysis of cITP (P = 0·038). The heterozygous V/F genotype of FCGR3A was increased in cITP patients compared with controls (62% versus 41%, P = 0·017, OR = 2·38; 95% CI 1·09–5·32). In an analysis of polymorphisms in pro-inflammatory cytokines, an overall association was observed at both the TNF (P = 0·0031) and the LTA loci (P = 0·019). Analysis of the remaining six genes, IL1A, IL1B, IL1RN, IL4, IL6 or IL10, was not informative. For the TNF (−308) polymorphism, the 1/2 or 2/2 genotypes were observed in 11% of cITP patients compared with 29% of controls (P = 0·027(f), OR = 0·31; 95% CI 0·08–0·94), suggesting that allele 1 is over-represented in cITP. For LTA, genotype 2/2 was over-represented in patients compared with controls (62% versus 38%, P = 0·0070, OR = 2·66; 95% CI: 1·22–5·96).
In an exploratory analysis, the contribution of genotype combinations to cITP was examined (see Table II). Children with cITP were more likely to possess both the TNF (−308) 1/1 genotype and the FCGR3A V/F genotype (59% versus 29%, P = 0·0003, OR = 3·64; 95% CI: 1·65–8·13). A similar effect was observed for LTA and FCGR3A at-risk genotypes (43% versus 17%, P = 0·0004, OR = 3·78; 95% CI: 1·62–8·63). Similarly, 81% of children with cITP possessed one or both of the higher risk variant genotypes of FcγRs (FCGR3A V/F or FCGR3B NA1/NA1) versus 50% of controls (P = 0·0005, OR = 4·33; 95% CI: 1·74–12·20). Eighty-one percent of children with cITP had a FCGR3A genotype with at least one V allele or had the FCGR3A FF genotype but were homozygous for the FCGR3B NA1 genotype versus 60% of controls (P = 0·014, OR = 2·88; 95% CI: 1·16–8·15).