Antivir Ther. 2017 Mar 14. doi: 10.3851/IMP3154. [Epub ahead of print]
Association of vitamin-D-related genetic variations and treatment response to pegylated interferon in patients with chronic hepatitis B.Limothai U1, Chuaypen N2, Khlaiphuengsin A2, Chittmittraprap S2, Poovorawan Y1, Tangkijvanich P2. Author information 1Center of Excellence in Clinical Virology, Department of Pediatrics, Chulalongkorn University, Bangkok, Thailand.2Research Unit of Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
AbstractBACKGROUND: Vitamin D, a potent immune-modulator, has been linked to the pathogenesis of chronic hepatitis B (CHB). This study was aimed at investigating the association between single nucleotide polymorphisms (SNPs) in vitamin D-related genes and treatment response to pegylated interferon (PEG-IFN) in patients with CHB.
METHODS: A total 275 Thai patients (122 HBeAg-positive and 153 HBeAg-negative CHB) treated with 48-week PEG-IFN were recruited. Virological response (VR) at 48 weeks post treatment was defined as HBeAg seroconversion plus HBV DNA <2,000 IU/mL for HBeAg-positive CHB and HBV DNA <2,000 IU/mL for HBeAg-negative CHB. The SNPs VDR (rs2228570), DBP (rs7041) and CYP27B1 (rs4646536) were analyzed.
RESULTS: The distribution of TT, CT and CC genotypes of rs4646536 in this cohort was 21.8%, 46.2% and 32.0%, respectively. There was no different in its distribution according to HBeAg status. In HBeAg-positive CHB, patients with TT genotype, compared with non-TT genotype, achieved higher VR (53.3% vs. 31.5%; P=0.032) and HBsAg clearance (20.0% vs. 5.4%; P=0.016). In HBeAg-negative CHB, the corresponding figures were 60.0% vs. 30.9% (P=0.003) and 16.7% vs. 5.7% (P=0.045), respectively. Patients with TT-genotype had more rapid HBsAg decline than those with non-TT genotype. However, SNPs rs2228570 and rs7041were not associated with VR and HBsAg clearance. Logistic regression analysis demonstrated that SNP rs4646536 and baseline HBsAg level were independent predictors of VR in both HBeAg-positive and HBeAg-negative CHB.
CONCLUSIONS: Our data suggest that SNP rs4646536 in the CYP27B1 gene is a predictive factor of response to PEG-IFN therapy in Thai patients with CHB.
招募总共275名泰国患者（122 HBeAg阳性和153 HBeAg阴性CHB）用48周PEG-IFN治疗。治疗后48周的病毒学反应（VR）定义为HBeAg血清转化加HBeAg阳性CHB的HBV DNA <2,000 IU / mL和HBeAg阴性CHB的HBV DNA <2,000 IU / mL。分析SNP VDR（rs2228570），DBP（rs7041）和CYP27B1（rs4646536）。
结果：
该队列中rs4646536的TT，CT和CC基因型的分布分别为21.8％，46.2％和32.0％。根据HBeAg状态，其分布没有不同。在HBeAg阳性CHB中，与非TT基因型相比，TT基因型患者获得更高的VR（53.3％对31.5％; P = 0.032）和HBsAg清除率（20.0％对5.4％; P = 0.016）。在HBeAg阴性CHB中，相应的数字分别为60.0％对30.9％（P = 0.003）和16.7％对5.7％（P = 0.045）。与非TT基因型相比，TT基因型患者的HBsAg下降更快。然而，SNP rs2228570和rs7041与VR和HBsAg清除率无关。 Logistic回归分析表明，SNP rs4646536和基线HBsAg水平是HBeAg阳性和HBeAg阴性CHB中VR的独立预测因子。
结论：