Association Of Mitochondrial DNA Haplogroups With HBV Infection And Clinical Outcomes

Objectives:The genetic variation and haplogroups information of mitochondrial DNA control region were obtained from chronic HBV infection population,HBV spontaneously recovering population and healthy population.The distribution of mitochondrial DNA mutation locus and haplogroups were studied.Then the differences of variance and haplogroups were analyzed.Lastly with combination of clinical data,the ralationship were explored between candidate mitochondrial DNA mutation and haplogroups with HBV susceptibility and outcome of HBV infection.Methods:We first measured the mitochondrial DNA control region of peripheral blood from 234 HBV spontaneously recovering population from the Liver Disease Medicine and Physical Examination Center of the Second People's Hospital of Yunnan Province.Then we integrate the data of previous research,including 272 chronic HBV infection population,312 healthy population,to analyze control region of mitochondrial DNA.The data obtained were compared with the revised Cambridge Refrence Sequence(revised Cambridge Reference Sequence;PCR)5 and we recorded germline mutations in all individual mitochondrial DNA control regions.Based on the mutation information,we reference the mitochondrial DNA phylogenetic tree of the exist world population to divide the mitochondrial DNA data of the study population into a specific haplogroup.Through the X2 test,we analyzed the frequency of mitochondrial DNA control region mutation and haplogroup distribution in chronic HBV infection population,HBV spontaneously recovering population and healthy population.At last with the combination of clinical information,the relationship between distribution frequency of mitochondrial DNA haplogroup and clinical features was analysed.Results:1 The mtDNA D-loop region sequence results:totally there were 818 mtDNA control region sequences of peripheral blood from 272 HBV infected people,234 spontaneously HBV-resolved individuals and 312 healthy people from the Liver Disease Medicine and Physical Examination Center of the Second People's Hospital of Yunnan Province,with the length of 1124 bp.There were 280 polymorphic loci in the chronic HBV infection group,272 polymorphic loci in the HBV spontaneously recovering group and 297 polymorphic loci in the healthy control group.Among them,there were 194 polymorphic loci in the chronic HBV infection group and the healthy control group,and 85 were specific for the chronic HBV infection group.There were 230 polymorphic loci in chronic HBV infection group and HBV spontaneously recovering group,and 50 were specific for chronic HBV infection group.There were 168 polymorphic loci in the self-limiting HBV infection group and the healthy control group,and 104 specific loci of the HBV spontaneously recovering group.818 sequences were successfully classified haplogroups,of which were 700 sequences into 14 categories(HBV infected with 231,HBV spontaneously recovering 207 and healthy with 262),respectively M*?M7?M8?C?D?D4?D5?A?R9?F?F1?B?B4?B5.Meanwhile,a total of 118 sequences were not included in the above 14 haplogroups(HBV infected with 41,HBV spontaneously recovering 27 and healthy with 50.With the combination of previous research,the data was analysed by principal component analysis and hierarchy.The analysis result proven that chronic HBV infection patients,HBV spontaneously recovering people and healthy people were from a same place.2 The mtDNA control region mutation site was X2 test.The distribution of the mutation sites in the HBV infected and the healthy control group showed that the frequency of m.151C>T mutation in patients with chronic HBV infection population(2.12%)was significantly lower than that of the healthy population(7.37%).The distribution of the mutation sites in the chronic HBV infection population and the HBV spontaneously recovering population showed that the frequency of m.146T>C?m.310C>T?m.310+C?m.523-524AC/del mutation in patients with chronic HBV infection population(15.81%,20.22%,70.22%,41.18%)was significantly higher than that of the HBV spontaneously recovering population(8.54%,11.54%,53.85%,25.64%).The frequency of m.315+C?m.16274C>T mutation in patients with chronic HBV infection population(5.88%,3.30%)lower than that of the HBV spontaneously recovering population(26.92%,7.26%).The distribution of the mutation sites in the HBeAg positive and the HBeAg negative group showed that the frequency of m.16266C>T mutation in HBeAg positive chronic HBV infection people(9.68%)higher than that of the HBeAg negative chronic HBV infection people(2.38%).3 The distribution of mitochondrial DNA haplotype D5 between HBV infected patients and healthy people showed that the frequency of mitochondrial DNA haplotype D5 in HBV infected patients(8.09%)higher than that of the healthy people(3.20%).The distribution of mitochondrial DNA haplotype D5 between HBV infected patients and HBV spontaneously recovering people showed that the frequency of mitochondrial DNA haplotype D5 in HBV infected patients(8.09%)higher than that of HBV spontaneously recovering people(3.84%).There was no difference in the distribution of mitochondrial DNA haplotype among healthy and HBV-infected population,HBeAg positive and HBeAg negative chronic HBV infection people.4 The chronic HBV infection people,HBV spontaneously recovering people,healthy people,HBeAg positive and HBeAg negative chronic HBV infection people of carrying haplogroup D5 and non-carrying haplogroup D5 within the group there are no difference with gender,age and liver function index.5 Distribution of mtDNA haplogroups after stratification by gender.The distribution of mitochondrial DNA haplogroups showed that there were no significant differences.Conclusions:1 The frequency of m.151C>T mutation in patients with chronic HBV infection was significantly lower than that of the healthy control,which suggested that the one site mutations may be a potential protective factor chronic HBV infection,or people who without those mutations was susceptibility to HBV.2 The frequency of m.146T>C?m.310C>T?m.310+C?m.523-524AC/del mutation in patients with chronic HBV infection was significantly higher than that of the HBV spontaneously recovering people,which suggested that the four site mutations may be a potential risk factor chronic HBV infection.The frequency of m.315+C?m.16274C>T mutation in patients with chronic HBV infection lower than that of the HBV spontaneously recovering people,which suggested that the two site mutations may be related to HBV clearance.3 The frequency of m.16266C>T mutation in HBeAg positive chronic HBV infection people higher than that of the HBeAg negative chronic HBV infection people,which suggested that the one site mutations may be associated with chronic infection outcome of HBV.4 mtDNA haplotype D5 may be a risk factor for persistent infection of HBV,and is not associated with gender,age,and liver function.