Correlations between mitochondrial DNA haplogroup D5 and chronic hepatitis B virus infection in Yunnan, China

Xiao Li, Tai-Cheng Zhou, Chang-Hui Wu, Li-Lin Tao, Rui Bi, Li-Jun Chen, De-Yao Deng, Chang Liu, Newton O Otecko, Yang Tang, Xin Lai, Liang Zhang, Jia Wei, Xiao Li, Tai-Cheng Zhou, Chang-Hui Wu, Li-Lin Tao, Rui Bi, Li-Jun Chen, De-Yao Deng, Chang Liu, Newton O Otecko, Yang Tang, Xin Lai, Liang Zhang, Jia Wei

Abstract

Mitochondrial abnormality is frequently reported in individuals with hepatitis B virus (HBV) infection, but the associated hosts' mitochondrial genetic factors remain obscure. We hypothesized that mitochondria may affect host susceptibility to HBV infection. In this study, we aimed to detect the association between chronic HBV infection and mitochondrial DNA in Chinese from Yunnan, Southwest China. A total of 272 individuals with chronic HBV infection (CHB), 310 who had never been infected by HBV (healthy controls, HC) and 278 with a trace of HBV infection (spontaneously recovered, SR) were analysed for mtDNA sequence variations and classified into respective haplogroups. Haplogroup frequencies were compared between HBV infected patients, HCs and SRs. Haplogroup D5 presented a higher frequency in CHBs than in HCs (P = 0.017, OR = 2.87, 95% confidence interval [CI] = (1.21-6.81)) and SRs (P = 0.049, OR = 2.90, 95% CI = 1.01-8.35). The network of haplogroup D5 revealed a distinct distribution pattern between CHBs and non-CHBs. A trend of higher viral load among CHBs with haplogroup D5 was observed. Our results indicate the risk potential of mtDNA haplogroup D5 in chronic HBV infection in Yunnan, China.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Principal component analysis of CHBs, SRs and HCs from Yunnan province in Southwest China and the previously reported Han Chinese populations across China. (a) PC map of Han regional populations based on mtDNA haplogroup frequencies. Sample sets in this study were marked by solid triangles. The reported Han Chinese populations (data shown in Supplementary Table S3) were marked by hollow circles. The abbreviations of Han regional populations were the same with those in Supplementary Table S3. (b) Plot of mtDNA haplogroup contribution to the first and second PCs. Abbreviations: PC, principal component.
Figure 2
Figure 2
Network of haplogroup D5 in CHBs and combined controls consists of SRs and HCs. The variant order of the mtDNA control region is arbitrary on the branch. Each circle represents a kind of mtDNA haplogroup. The area of each circle is proportional to the haplogroup frequency. Sample sizes of the smallest and the largest sub-lineages were labeled in the corresponding circles. Length mutation of C-tract in region 16184–16193 was not considered during the network construction. The asterisks denote ancestral nodes of haplogroup D5.
Figure 3
Figure 3
Viral load of serum HBV-DNA in CHBs belonging to haplogroup D5 and non-D5. We divided the viral load into five categories arbitrarily. The horizontal axis represents the viral load of serum HBV-DNA. The vertical axis represents the proportion of participants whose viral load falls in the respective viral load categories among CHBs with D5 or other haplogroup backgrounds.
Figure 4
Figure 4
Clinical parameters of liver function in CHBs belonging to haplogroup D5 and non-D5. Serum levels of ALT (alanine transaminase), AST (aspartate aminotransferase), TBIL (total bilirubin), DBIL (direct bilirubin), TP (total protein) and ALB (albumin) were compared between D5 and non-D5 haplogroup members. Horizontal lines across the plots mark the mean expression level. Asterisk indicates significant difference (P < 0.05).

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