As shown in Table 2, the P buy RG7204 values were quite
similar (P = 2.70 × 10−11 to 0.003) for 11 SNPs located at HLA-DP, while rs11752643 remained nonsignificant. For 11 significant SNPs, we examined the association of genotype frequencies between cases and controls (both clearance and healthy combined), and also between cases and clearance controls only. Table 3 presents the genotype distribution in each group: OR with 95% CI and P values for carriers versus controls, and carriers versus clearances. As illustrated in Fig. 1, the first five SNPs showed minor alleles (four in HLA-DPA1 and one adjacent within HLA-DPB1) associated with decreasing risk/protection of HBV chronic infection (Table 3; OR = 0.33 to 0.66, P = 6.7 × 10−7 to 0.045 for homozygote, OR = 0.50 to 0.77, P = 4.6 × 10−7 to 0.036 for heterozygote). The first four SNPs located in HLA-DPA1 formed haplotype block 1 (Fig. 1). The last six variants located on gene HLA-DPB1 had minor alleles significantly associated with increasing risk/susceptibility of HBV chronic infection (OR = 2.46 to 3.34, P = 5.7 × 10−12 to 7.0 × 10−7 for homozygote, OR = 1.56 to 2.36, P = 6.0 × 10−9 to 0.004 for heterozygote). These six SNPs with susceptibility selleck compound minor alleles
formed haplotype block 2 (Fig. 1). Similar significant associations were observed when we compared HBV carriers with HBV clearances (Table 3; columns 8, 9). Next we examined haplotype association for block 1, block 2, and the two blocks combined. Table 4 lists the haplotype frequencies in cases and controls, OR with 95% CI and P values for block 1 and block 2. The haplotype AACT, which retains all rare protective alleles of block 1, was significantly associated with decreasing risk of chronic hepatitis B infection (OR = 0.54, P = 8.73 × 10−7). The haplotype GAGATT (which retains
all rare susceptible alleles of block 2) and GGGGTC (which retains three rare susceptible aminophylline alleles of block 2) were significantly associated with increased the risk of chronic hepatitis B infection (OR = 1.98, P = 1.37 × 10−10 for GAGATT; OR = 1.7 P = 0.002 for GGGGTC). Table 5 presents a combination of haplotype block 1 and block 2 considered together. The combined protective haplotypes of block 1 (AACT) and block 2 (AGTGCC) were very strongly associated with decreased risk of chronic hepatitis B (OR = 0.36, P = 3.0 × 10−11). The protective haplotype of block 2 (AGTGCC) combined with other haplotypes of block 1 were also significantly associated with decreased risk of chronic hepatitis B infection (OR = 0.56 to 0.65, P = 0.002 to 0.0002). In this study, 12 SNPs that were previously reported to be associated with chronic hepatitis B18, 19 were interrogated in 521 persistent chronic HBV carriers and 819 controls in a Han Chinese population from northern China. Eleven SNPs located within HLA-DPA1 and HLA-DPB1 were strongly significantly associated with persistent chronic HBV carrier status (Table 2).