Genome-Wide Association Study for Chronic Hepatitis B Infection in the Thai Population

被引：7

作者：

Ashouri, Saeideh ^{[1
,2
]}

Khor, Seik-Soon ^{[1
,2
]}

Hitomi, Yuki ^{[3
]}

Sawai, Hiromi ^{[2
]}

Nishida, Nao ^{[4
]}

Sugiyama, Masaya ^{[4
]}

Kawai, Yosuke ^{[1
,2
]}

Posuwan, Nawarat ^{[5
,6
]}

Tangkijvanich, Pisit ^{[7
]}

Komolmit, Piyawat ^{[8
,9
]}

Tsuiji, Makoto ^{[3
]}

Shotelersuk, Vorasuk ^{[10
]}

Poovorawan, Yong ^{[6
]}

Mizokami, Masashi ^{[4
]}

Tokunaga, Katsushi ^{[1
,2
]}

机构：

[1] Natl Ctr Global Hlth & Med, Genome Med Sci Project, Toyama, Tokyo, Japan

[2] Univ Tokyo, Grad Sch Med, Dept Human Genet, Tokyo, Japan

[3] Hoshi Univ, Dept Microbiol, Sch Pharm & Pharmaceut Sci, Tokyo, Japan

[4] Natl Ctr Global Hlth & Med, Genome Med Sci Project, Ichikawa, Chiba, Japan

[5] Thammasat Univ, Chulabhorn Int Coll Med, Rangsit Campus, Bangkok, Pathum Thani, Thailand

[6] Chulalongkorn Univ, Fac Med, Ctr Excellence Clin Virol, Dept Pediat, Bangkok, Thailand

[7] Chulalongkorn Univ, Fac Med, Ctr Excellence Hepatitis & Liver Canc, Bangkok, Thailand

[8] King Chulalongkorn Mem Hosp, Ctr Excellence Liver Dis, Thai Red Cross Soc, Bangkok, Thailand

[9] Chulalongkorn Univ, Fac Med, Liver Fibrosis & Cirrhosis Res Unit, Bangkok, Thailand

[10] Chulalongkorn Univ, Fac Med, Ctr Excellence Med Genom, Dept Pediat, Bangkok, Thailand

来源：

FRONTIERS IN GENETICS | 2022年 / 13卷

关键词：

chronic hepatitis B; GWAS; SNP; HLA; allele; haplotype; PHOSPHOLIPID SCRAMBLASE 1; GENE POLYMORPHISMS; VIRUS INFECTION; HEPATOCELLULAR-CARCINOMA; HBV INFECTION; CORE PROTEIN; SUSCEPTIBILITY; VARIANTS; RISK; LOCUS;

D O I：

10.3389/fgene.2022.887121

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

To identify novel host genetic variants that predispose to hepatitis B virus (HBV) persistence, we performed the first genome-wide association study in the Thai population involving 318 cases of chronic hepatitis B and 309 healthy controls after quality control measures. We detected the genome-wide significant association of the HLA class II region (HLA-DPA1/DPB1, rs7770370, p-value = 7.71 x 10(-10), OR = 0.49) with HBV chronicity. Subsequent HLA allele imputation revealed HLA-DPA1*01:03 (Pc = 1.21 x 10(-6), OR = 0.53), HLA-DPB1*02:01 (Pc = 2.17 x 10(-3), OR = 0.50), and HLA-DQB1*06:09 (Pc = 2.17 x 10(-2), OR = 0.07) as protective alleles, and HLA-DPA1*02:02 (Pc = 6.32 x 10(-5), OR = 1.63), HLA-DPB1*05:01 (Pc = 1.13 x 10(-4), OR = 1.72), HLA-DPB1*13:01 (Pc = 4.68 x 10(-2), OR = 1.60), and HLA-DQB1*03:03 (Pc = 1.11 x 10(-3), OR = 1.84) as risk alleles for HBV persistence. We also detected suggestive associations in the PLSCR1 (rs35766154), PDLIM5 (rs62321986), SGPL1 (rs144998273), and MGST1 (rs1828682) loci. Among single-nucleotide polymorphisms in the PLSCR1 locus, rs1061307 was identified as the primary functional variant by in silico/in vitro functional analysis. In addition to replicating the association of the HLA class II region, we detected novel candidate loci that provide new insights into the pathophysiology of chronic hepatitis B.

引用

页数：10

共 69 条

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