The minor alleles of five SNP loci (four on HLA-DPA1 and one in the HLA-DPB1 region) were protective from risk of chronic hepatitis B. The minor alleles of six SNP loci in the HLA-DPB1 gene region were susceptible to chronic hepatitis B (Tables 2, 3). A closely adjacent SNP, rs11752643, which did not track HLA DPA1 or HLA-DPB2, but which did show strong LD with

HLA-DR13, was not associated with chronic hepatitis B. Our results from an independent Han Chinese population replicated in SNP allele direction and statistical strength the reported Japanese/Thai GWAS association.19 The haplotypes directly inform how alleles are organized along the chromosome and may provide additional power for mapping disease genes; haplotypes also provide insight into factors influencing the dependency among genetic markers. The http://www.selleckchem.com/products/bgj398-nvp-bgj398.html haplotype-based methods can potentially capture cis-interactions between two or more causal variants. The haplotypes should be more informative than individual genotypes

for revealing disease-causing mechanisms at a candidate gene.23 Based on these assumptions, we explored the haplotype and joint haplotype association of significant SNPs with chronic hepatitis B infection. The dominant (major) alleles were risk alleles for rs2395309, rs3077, rs2301220, rs9277341, and rs3135021 in the Han Chinese population. The first four of these SNPs formed haplotype block 1; the haplotype GGTC combined by risk alleles was the most common haplotype (freq. = 0.577) in our cohort (Table 4, Fig. 2). The less common haplotype AACT (freq. = 0.209) combined by protective alleles was significantly associated with Rapamycin mw decreasing risk of chronic hepatitis B infection Isoconazole (Tables 2, 4). The dominant

alleles were protective allele for rs9277535, rs10484569, rs3128917, rs2281388, rs3117222, and rs9380343 located on HLA-DPB1 in our study population. These six SNPs formed haplotype block 2, the haplotype AGTGCC (freq. = 0.499) combined by protective alleles was the most common haplotype (Table 4, Fig. 2). The haplotype GAGATT (freq. = 0.327) combined by risk alleles was significantly associated with increasing risk of HBV chronic infection (OR = 1.98, P = 1.37 × 10−10; Table 4). The haplotype GGGGTC with three risk alleles was also associated with significant susceptibility to HBV chronic infection. We also tested the joint effects for haplotype block 1 and block 2. The susceptible haplotypes GGTC of block 1 and GAGATT of block 2 comprised the most common joint haplotype (Table 5). The joint haplotype of two protective haplotypes from block 1 and block 2 (AACT*AGTGCC) exerted a strong protective effect against HBV chronic infection (OR = 0.36, P = 3.03 × 10−11; Table 5). The joint haplotypes including the protective haplotype of block 2 (AGTGCC) showed significant protective effects as well (Table 5). These findings supported the single-SNP association results.