SEARCH · PubMed Health

Results for “mutation load”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 307 records · Page 17Linked to original sources

PubMed2003

Allelic heterogeneity in LINE-1 retrotransposition activity.

De novo LINE-1 (long interspersed element-1, or L1) retrotransposition events are responsible for approximately 1/1,000 disease-causing mutations in humans. Previously, L1.2 was identified as the likely progenitor of a mutagenic insertion in the factor VIII gene in a patient with hemophilia A. It subsequently was shown to be one of a small number of active L1s in the human genome. Here, we demonstrate that L1.2 is present at an intermediate insertion allele frequency in worldwide human populations and that common alleles (L1.2A and L1.2B) exhibit an approximately 16-fold difference in their ability to retrotranspose in cultured human HeLa cells. Chimera analysis revealed that two amino acid substitutions (S1259L and I1220M) downstream of the conserved cysteine-rich motif in L1 open reading frame 2 are largely responsible for the observed reduction in L1.2A retrotransposition efficiency. Thus, common L1 alleles can vary widely in their retrotransposition potential. We propose that such allelic heterogeneity can influence the potential L1 mutational load present in an individual genome.

Base Sequence↗

PubMed2006

Endurance training and detraining in mitochondrial myopathies due to single large-scale mtDNA deletions.

At present there are limited therapeutic interventions for patients with mitochondrial myopathies. Exercise training has been suggested as an approach to improve physical capacity and quality of life but it is uncertain whether it offers a safe and effective treatment for patients with heteroplasmic mitochondrial DNA (mtDNA) mutations. The objectives of this study were to assess the effects of exercise training and detraining in eight patients with single, large-scale mtDNA deletions to determine: (i) the efficacy and safety of endurance training (14 weeks) in this patient population; (ii) to determine the effect of more prolonged (total of 28 weeks) exercise training upon muscle and cardiovascular function and (iii) to evaluate the effect of discontinued training (14 weeks) upon muscle and cardiovascular function. Our results show that: (i) 14 weeks of exercise training significantly improved tolerance of submaximal exercise and peak capacity for work, oxygen utilization and skeletal muscle oxygen extraction with no change in the level of deleted mtDNA; (ii) continued training for an additional 14 weeks maintained these beneficial adaptations; (iii) the cessation of training (detraining) resulted in loss of physiological adaptation to baseline capacity with no overall change in mutation load. Patients' self assessment of quality of life as measured by the SF-36 questionnaire improved with training and declined with detraining. Whilst our findings of beneficial effects of training on physiological outcome and quality of life without increases in the percentage of deleted mtDNA are encouraging, we did not observe changes in mtDNA copy number. Therefore there remains a need for longer term studies to confirm that endurance exercise is a safe and effective treatment for patients with mitochondrial myopathies. The effects of detraining clearly implicate physical inactivity as an important mechanism in reducing exercise capacity and quality of life in patients with mitochondrial myopathy.

Adaptation, Physiological↗

PubMed2003

Associations between tissue-specific DNA alkylation, DNA repair and cell proliferation in the colon and colon tumour yield in mice treated with 1,2-dimethylhydrazine.

Putative risk factors (DNA damage) and risk modifying factors (DNA repair and cell proliferation) were examined in an experimental mouse model in which treatment with dimethylhydrazine (6.8 mg/kg DMH i.p. once weekly) for up to 20 weeks induces colon tumours in a site specific manner with 0, 43 and 87% of animals having proximal, mid and distal colon tumours respectively at the highest cumulative dose. Levels of the pro-carcinogenic DNA adduct, O(6)-methylguanine (O(6)-MeG), in colonic DNA were found to vary with time after final treatment and with location within the colon but not with total DMH dose. O(6)-MeG levels were generally lowest in proximal colon DNA and highest in distal colon DNA. Steady state O(6)-MeG levels were obtained at the highest cumulative DMH dose with O(6)-MeG levels in mid and distal colon DNA being 5 and 10 times higher those in proximal colon DNA. O(6)-alkylguanine-DNA alkyltransferase (MGMT) activity, and cell proliferation indices in the colon were also found to vary with time after final treatment but not with either location within the colon or total DMH dose. O(6)-MeG levels, MGMT activity and cell proliferation indices at specific time points as well as basal MGMT activity were not associated with differences in tumour yield within the colon. However tumour yield was associated with the cumulative amount of O(6)-MeG present in DNA over the treatment period and with the treatment induced cumulative increase in cell proliferation, particularly within regions of the colon crypt where stem cells reside but not with cumulative changes in MGMT activity. Results are consistent with an increased cancer risk arising from an increased mutation load in the target stem cell population due to increased adduct formation/persistence and cell proliferation but also suggest that other cell specific factors may help to determine tumourigenic response.

1,2-Dimethylhydrazine↗

PubMed2006

Replication in mammalian cells recapitulates the locus-specific differences in somatic instability of genomic GAA triplet-repeats.

Friedreich ataxia is caused by an expanded (GAA.TTC)n sequence in intron 1 of the FXN gene. Small pool PCR analysis showed that pure (GAA.TTC)44+ sequences at the FXN locus are unstable in somatic cells in vivo, displaying both expansions and contractions. On searching the entire human and mouse genomes we identified three other genomic loci with pure (GAA.TTC)44+ sequences. Alleles at these loci showed mutation loads of <1% compared with 6.3-30% for FXN alleles of similar length, indicating that somatic instability in vivo is regulated by locus-specific factors. Since distance between the origin of replication and the (CTG.CAG)n sequence modulates repeat instability in mammalian cells, we tested if this could also recapitulate the locus-specific differences for genomic (GAA.TTC)n sequences. Repeat instability was evaluated following replication of a (GAA.TTC)115 sequence in transfected COS1 cells under the control of the SV40 origin of replication located at one of five different distances from the repeat. Indeed, depending on the location of the SV40 origin relative to the (GAA.TTC)n sequence, we noted either no instability, predominant expansion or both expansion and contraction. These data suggest that mammalian DNA replication is a possible mechanism underlying locus-specific differences in instability of GAA triplet-repeat sequences.

Adult↗

PubMed1985

Reverse transcription in the eukaryotic genome: retroviruses, pararetroviruses, retrotransposons, and retrotranscripts.

Recent studies indicate that greater than 10% of the human and mouse genome appears to consist of integrated DNA copies of RNA molecules. These sequences include retroviruses, retrovirus-like DNAs, retrotransposons, and retrotranscripts and represent more than 500,000 separate integration events. The nature of the enzymes used for the reverse transcription from RNA to DNA and for integration of the DNA copies into chromosomal DNA is unknown. A major evolutionary effect of these integrations would have been mutation. Thus, present-day organisms are those that survived this mutational load.

Animals↗

PubMed2004

Patterns of evolutionary constraints in intronic and intergenic DNA of Drosophila.

We develop methods to infer levels of evolutionary constraints in the genome by comparing rates of nucleotide substitution in noncoding DNA with rates predicted from rates of synonymous site evolution in adjacent genes or other putatively neutrally evolving sites, while accounting for differences in base composition. We apply the methods to estimate levels of constraint in noncoding DNA of Drosophila. In introns, constraint (the estimated fraction of mutations that are selectively eliminated) is absolute at the 5' and 3' splice junction dinucleotides, and averages 72% in base pairs 3-6 at the 5'-end. Constraint at the 5' base pairs 3-6 is significantly lower in the lineage leading to Drosophila melanogaster than in Drosophila simulans, a finding that agrees with other features of genome evolution in Drosophila and indicates that the effect of selection on intron function has been weaker in the melanogaster lineage. Elsewhere in intron sequences, the rate of nucleotide substitution is significantly higher than at synonymous sites. By using intronic sites outside splice control regions as a putative neutrally evolving standard, constraint in the 500 bp of intergenic DNA upstream and downstream regions of protein-coding genes averages approximately 44%. Although the estimated level of constraint in intergenic regions close to genes is only about one-half of that of amino acid sites, selection against single-nucleotide mutations in intergenic DNA makes a substantial contribution to the mutation load in Drosophila.

Animals↗

PubMed2004

On the neutrality of molecular genetic markers: pedigree analysis of genetic variation in fragmented populations.

Many studies employ molecular markers to infer ecological and evolutionary processes, assuming that variation found at genetic loci offers a reliable representation of stochastic events in natural populations. Increasingly, evidence emerges that molecular markers might not always be selectively neutral. However, only a few studies have analysed how deviations from neutrality could affect estimates of genetic variation, using populations with known genealogy. We monitored changes in allozyme variation over eight generations in captive metapopulations of the butterfly Bicyclus anynana. Population demography was recorded by individually marking 35 000 butterflies and constructing pedigrees. We designed a computer program that simulated the inheritance of founder allozyme alleles in butterfly pedigrees. We thus tested whether the observed transmission of allozyme alleles could be explained by random genetic drift alone, or whether there was evidence for positive or negative selection. This analysis showed that in the smallest metapopulations the loss of allozyme variation exceeded the neutral rate. Possibly, linkage disequilibria between deleterious mutations and marker alleles resulted in background selection and a faster erosion of allozyme variation. In larger metapopulations, one locus (MDH) showed a significant heterozygote excess and smaller than expected loss in heterozygosity, observations consistent with (associative) overdominance. This study demonstrates that the neutrality of molecular markers cannot always be assumed, particularly in small populations with a high mutation load.

Animals↗

PubMed2005

Exo+ proofreading polymerases mediate genetic analysis and its application in biomedical studies.

Polymerases with a proofreading function in their internal 3' to 5' exonuclease possess high fidelity for DNA replication both in vivo and in vitro. The obstacle facing Exo+ polymerases for single nucleotide polymorphism (SNP) detection could be bypassed by using primer-3'-termini modification. This hypothesis has been well tested using three types of modified allele specific primers with: 3' labeling, 3' to 5' exonuclease resistance, and 3' dehydroxylation. Accordingly, three new SNP assaying methods have been developed to carry out genome-wide genotyping, taking advantage of the enzymatic properties of Exo+ polymerases. These new mutation detection assays are widely adaptable to a variety of platforms, including multi-well plate and microarray technologies. Application of Exo+ polymerases to genetic analysis, including genotyping that is mostly relevant to pharma-cogenetics, high-fidelity gene expression profiling, rare mutation detection and mutation load assay, will help to accelerate the pace of personalized medicine. In this review paper, we will first introduce three new assays that we have recently developed, and then describe a number of their applications in pharmacogenetics and in other biomedical studies.

DNA Primers↗

PubMed2025

Comparative genomic analysis of Acer tsinglingense and A. davidii provides insights into nervonic acid biosynthesis, population evolution and genome vulnerability of endangered A. tsinglingense.

Global biodiversity is facing threats from climate change, habitat fragmentation, and anthropogenic activities-pressures that particularly endanger endemic and narrowly distributed species. In this study, the high-quality chromosome-level genomes of two ecologically divergent maples were assembled: the endangered and range-restricted Acer tsinglingense (791.40 Mb) and its widespread congener Acer davidii (1291.99 Mb). Phylogenomic analysis indicates that the two species diverged ~16.3 million years ago, with A. tsinglingense showing notable gene family expansions in secondary metabolite pathways. Notably, the 3-ketoacyl-CoA synthase gene family, which is involved in nervonic acid biosynthesis, underwent significant expansion and tandem duplication in A. tsinglingense, exhibiting high expression in buds. Population genomic analysis revealed that, compared with the widely distributed A. davidii, A. tsinglingense possesses lower genetic diversity, higher harmful mutation load, and signatures of a severe population bottleneck during the Late Pleistocene. Genome-environment association analysis further identified climate-adaptive genomic variations linked to five key environmental factors and projected potential genomic offsets under future climate scenarios. The southern lineage of A. tsinglingense exhibited greater climate sensitivity and genomic vulnerability under strong selective pressures, underscoring its importance as a conservation priority. Our research reveals that metabolic specializations in A. tsinglingense (such as the synthesis of nervonic acid) may confer competitive advantages in specific habitats. However, factors including its restricted distribution, historical population bottlenecks, and accumulated genetic load severely constrain its evolutionary potential to cope with rapid climate change. These findings emphasize the importance of elucidating the genomic basis and mechanisms of endangerment in metabolically specialized and threatened plant species to inform effective conservation strategies.

Genome, Plant↗

PubMed2005

Mobile genetic elements and sexual reproduction.

Transposable elements (TE) are prominent components of most eukaryotic genomes. In addition to their possible participation in the origin of sexual reproduction in eukaryotes, they may be also involved in its maintenance as important contributors to the deleterious mutation load. Comparative analyses of transposon content in the genomes of sexually reproducing and anciently asexual species may help to understand the contribution of different TE classes to the deleterious load. The apparent absence of deleterious retrotransposons from the genomes of ancient asexuals is in agreement with the hypothesis that they may play a special role in the maintenance of sexual reproduction and in early extinction for which most species are destined upon the abandonment of sex.

Animals↗

PubMedDate not supplied

Spontaneous cell transformation: karyoplasts derived from multinucleated cells produce new cell growth in senescent human epithelial cell cultures.

Previously, it was shown that SV40-induced cell transformation of human diploid (2N), epithelial cells was a dynamic process of nuclear and cellular events. In this process, nuclei of polyploid (above 2N) cells broke down into multinucleated cells (MNCs) by amitotic division. An induced mass karyoplast (i.e., small cell with reduced amount of cytoplasm) budding process from the MNCs produced transformed cells with extended life span (EL) and altered morphology. In this study, without the use of SV40 and no induction of karyoplast budding, the same sequence of cellular events was found to occur spontaneously for the same type of cells at replicative senescence (no mitosis). These cell transformation events were followed by phase-contrast photography of living cell cultures. Primary, diploid, epithelial cell cultures grew for two to three passages and then entered senescence. Cells remaining in the cultures after widespread cell death (mortality stage 1; M1) developed the typical large, flat-cell morphology of senescence with increased cytoplasmic volume. Some of these cells were MNCs, mostly with two to four nuclei. Cytokinesis in MNCs and spontaneous karyoplast budding from MNCs were observed, and new, limited EL cell growth was present either in foci of cells or as prolonged cell growth over one to two passages. At the end of their replicative phase, the EL cells entered another death crisis (M2) from which no cells survived. In M2-crisis, rarely transformed cells appear with immortal cell growth characteristics (i.e., cell lines). Numerous examples of fragmentation or amitosis of polyploid nuclei in the production of multinucleated cells (MNCs) are presented. Such nuclear divisions produced nuclei with unequal sizes, which suggest unbalanced chromosomal segregations. The nuclear and cellular events in cell transformation are compared with a natural (no induction) occurrence of MNC-offspring cells in mammalian placentas. The possibility of a connection between these two processes is discussed. And finally the difference in the duration of EL cell growth from SV40-MNCs versus from senescent-MNCs is ascribed to increased mutational load in SV40-induced MNCs as compared with that in senescence MNCs.

Amniocentesis↗

PubMed2005

Differential expression of KCNQ4 in inner hair cells and sensory neurons is the basis of progressive high-frequency hearing loss.

Human KCNQ4 mutations known as DFNA2 cause non-syndromic, autosomal-dominant, progressive high-frequency hearing loss in which the cellular and molecular basis is unclear. We provide immunofluorescence data showing that Kcnq4 expression in the adult cochlea has both longitudinal (base to apex) and radial (inner to outer hair cells) gradients. The most intense labeling is in outer hair cells at the apex and in inner hair cells as well as spiral ganglion neurons at the base. Spatiotemporal expression studies show increasing intensity of KCNQ4 protein labeling from postnatal day 21 (P21) to P120 mice that is most apparent in inner hair cells of the middle turn. We have identified four alternative splice variants of Kcnq4 in mice. The alternative use of exons 9-11 produces three transcript variants (v1-v3), whereas the fourth variant (v4) skips all three exons; all variants have the same amino acid sequence at the C termini. Both reverse transcription-PCR and quantitative PCR analyses demonstrate that these variants have differential expression patterns along the length of the mouse organ of Corti and spiral ganglion neurons. Our expression data suggest that the primary defect leading to high-frequency loss in DFNA2 patients may be attributable to high levels of the dysfunctional Kcnq4_v3 variant in the spiral ganglion and inner hair cells in the basal hook region. Progressive hearing loss associated with aging may result from an increasing mutational load expansion toward the apex in inner hair cells and spiral ganglion neurons.

Animals↗

PubMed2003

Expression of activation-induced cytidine deaminase is confined to B-cell non-Hodgkin's lymphomas of germinal-center phenotype.

Activation-induced cytidine deaminase (AID) is essential for somatic hypermutation and class switch recombination of the immunoglobulin (IG) genes in B cells. It has recently been proposed that AID, as the newly identified DNA mutator in man, may be instrumental in initiation and progression of B-cell non-Hodgkin's lymphomas (B-NHL). We quantitatively measured, by real-time reverse-transcription PCR, expression of AID and of the error-prone DNA polymerase iota in normal B cells and a comprehensive panel of B-NHL entities. In pre- and postgerminal center (GC)-type B-NHLs like in normal naive and memory cells, AID did not exceed background levels. However, half of Burkitt lymphomas tested were found to express AID, at most at levels comparable with those found in normal GC B cells. Thirty percent of diffuse large B-cell lymphomas also transcribed AID, some at supraphysiological levels. Of follicular lymphoma cases, only 25% expressed significant amounts of AID. Moreover, within the group of GC-type B-NHLs, a statistically significant correlation between AID and polymerase iota expression was found. By contrast, we observed no correlation between AID expression and mutation load neither with the degree of intraclonal diversity of IG variable heavy chain genes. Interestingly, in two of seven follicular lymphomas with clinical and histological progression, selective outgrowth of AID-expressing clones occurred, suggestive for a role of the somatic diversification machinery in lymphoma transformation.

Actins↗

PubMed2005

Clinical and microdissection genotyping analyses of the effect of intra-arterial cytoreductive chemotherapy in the treatment of lacrimal gland adenoid cystic carcinoma.

PURPOSE: To determine the effect of intra-arterial cytoreductive chemotherapy (IACC) as an adjunct of a multimodality protocol for the treatment of lacrimal gland adenoid cystic carcinoma (ACC). METHODS: This was a retrospective, comparative, consecutive case series. Nine consecutive patients with lacrimal gland ACC were treated with IACC, followed by orbital exenteration and chemoradiotherapy. This case series was compared with a series of seven patients treated by conventional local therapies. Clinical records, imaging studies, histologic sections, and archival specimens from all 16 patients were reviewed. Information analyzed included site of disease, histologic characteristics, extent of disease, local-regional recurrence or distant metastases, and disease-free survival time. Gene analysis was performed on microdissected tissue samples. Mutational allelotyping targeting nine genomic loci using 15 polymorphic microsatellite markers situated in proximity to known tumor suppressor genes serve as markers for the presence of gene deletion. The effect of IACC was assessed by the radiographic response and survival outcome in comparison to a historical cohort of patients managed by conventional local therapies. A fractional mutation index was used to compare the acquired mutational load between different tumors having nonidentical patterns of microsatellite informativeness. RESULTS: The carcinoma cause-specific death rates between the two treatment groups was significant (P = .029, log-rank test). The cumulative 5-year carcinoma cause-specific death rate was 16.7% in the IACC-treated group compared with 57.1% in the conventional treatment group. 1p36 was the single most common site affected by allelic loss for microsatellite markers in this series. CONCLUSIONS: The preliminary data suggest that IACC as an integral component of a multimodal treatment strategy is potentially effective in improving local disease control and overall disease-free survival in lacrimal gland ACC. Allelic loss for microsatellite markers at 1p36 may be a common and an early event in ACC formation and progression.

Adult↗

PubMed1997

Diffuse large cell lymphomas are derived from mature B cells carrying V region genes with a high load of somatic mutation and evidence of selection for antibody expression.

In the Revised European American Lymphoma (REAL) classification, several subtypes of high-grade lymphomas were combined in the entity diffuse large cell lymphoma (DLL). In the present study, a total of 19 cases of DLL (10 cases of centroblastic lymphoma, 5 cases of mediastinal B cell lymphoma, 2 cases of immunoblastic lymphoma, 1 case of T cell-rich B lymphoma and one case of large cell anaplastic lymphoma) were analyzed for somatically mutated immunoglobulin V region genes. Somatic mutations are acquired in the course of the germinal center (GC) reaction and are thus found in GC B cells and their descendants, i.e. memory B cells. The V gene sequences revealed that the tumor cells of all five subtypes of DLL harbored mutated V region genes and are thus derived from antigen-experienced (post) GC B cells. This indicates that from the point of view of the stage of development of the tumor precursor, the combination of those five subtypes to one entity, i.e. DLL, seems reasonable. In some cases, an unusually high frequency of somatic mutations was detected. This may indicate that DLL are derived from GC B cells, which, due to transforming events, stayed in the GC for prolonged periods of time, thereby accumulating a high load of somatic mutation. An analysis of the mutation pattern suggests that the tumor clone or its precursor were selected for antibody expression while acquiring somatic mutations. The latter observation discriminates DLL from classical Hodgkin's disease, where we recently also observed a high load of somatic mutation within rearranged V region genes, but a frequent occurrence of crippling mutations.

Adult↗

PubMed2004

Mutation and epimutation load in haploid and diploid life forms.

Epigenetic differentiation is the potentially heritable changes in levels of gene expression not caused by DNA sequence changes. Here, a classification scheme of mutations and epimutations is introduced, enabling a simple analysis of mutation and epimutation load in haploid and diploid organisms. It is found that the deleterious effect of epimutations is mainly determined by epimutation rate and degree of reversibility. Inherited epimutations have the same fitness consequences as inherited mutations. With complete reversibility and no inheritance, then epimutations have the same fitness consequences as somatic mutations. It is argued that organisms with somatic inheritance may experience more genetic load than organisms without somatic inheritance due to inherited epimutations in the former. This may partly explain the maintenance of soma/germ differentiation in many life forms. It is also argued that masking of deleterious somatic mutations may not necessarily explain the evolution of diploidy in life forms with inherited epimutations.

Animals↗

PubMed1995

In vivo assessment of mutations in the phenylalanine hydroxylase gene by phenylalanine loading: characterization of seven common mutations.

UNLABELLED: Mutations in the gene encoding phenylalanine hydroxylase (PAH) cause persistent hyperphenylalaninaemia. To date, more than 200 point mutations and microdeletions have been characterized. Each mutation has a particular quantitative effect on enzyme activity and recessive expression of different mutant alleles results in a marked interindividual heterogeneity of metabolic and clinical phenotypes. In this paper we demonstrate how a simple clinical test can be used to evaluate the correlation between mutation genotype and phenylalanine metabolism. In hyperphenylalaninaemic patients with known PAH mutation genotype, we have investigated phenylalanine turnover in vivo by measuring the ability to eliminate a test dose of L-phenylalanine. All patients could be considered functionally hemizygous for one of their mutant alleles by carrying on the other allele a mutation that is known to completely abolish PAH activity and encode a peptide with no immunoreactivity. Seven mutations (R408W, IVS-12nt1, R261Q, G46S, Y414C, A104D, and D415N) were characterized by oral phenylalanine loading, each mutation being represented by at least three patients. The elimination profile determined for a 3-day period provides a measure to compare residual activity of the mutant proteins and to assign each mutation to a particular metabolic phenotype. The established relation between genotype and phenotype may enable prediction of the severity of the disease by genotype determination in the newborn period. This will aid in the management of hyperphenylalaninaemia and may improve prognosis. CONCLUSION: The possibility of predicting the residual enzyme activity by DNA analysis performed already in the newborn period allows the prompt implementation of a diet that is adjusted to the degree of PAH deficiency. This may improve management and prognosis of hyperphenylalaninaemia.

Alleles↗

PubMed2006

Association of core promoter/precore mutations and viral load in e antigen-negative chronic hepatitis B patients.

Apart from core promoter A1762T/G1764A and precore G1896A mutations, other hepatitis B virus (HBV) mutants are detected in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB). The aim of this study was to determine the effects of those mutants on clinical manifestation and viral loads of genotypes B and C HBV. Seventy-nine HBeAg-negative CHB patients with hepatitis flare were enrolled in this study and their HBV precore/core region were sequenced. Serial biochemical profiles and viral loads were assessed and compared. Fifty-three patients (67%) were infected by genotype B HBV and 26 (33%) were infected by genotype C HBV. The clinical manifestation and HBV viral loads were comparable between the two groups. However, genotype B was significantly associated with precore G1896A mutation (92.5%), and more mutations within nucleotide 1809-1817 were detected in patients infected by genotype B as compared with those infected by genotype C (18.9%vs 3.8%). Most of the cases had mutations at the -2, -3 or -5 position from the precore AUG initiation codon. Triple core promoter mutations T1753C/A1762T/G1764A [corrected] appeared to be linked to genotype C rather than genotype B HBV (19.2%vs 1.9%; P = 0.013). In multivariate analysis, the presence of either triple core promoter 1753/1762/1764 mutation or nucleotide 1809-1817 mutation was the only factor associated with lower HBV viral load (<70 Meq/mL) (odds ratio = 9.01; 95% CI 1.11-71.43; P = 0.04). In conclusion, minor HBV variants with mutations in the core promoter and precore region were detectable in genotypes B and C. Such HBV variants are genotype specific and related to viraemia levels.

Adult↗