Association of mitochondrial DNA haplogroup and hearing impairment with aging in Japanese general population of the Iwaki Health Promotion Project

Age-related hearing loss (ARHL) is a complex multifactorial disorder. Studies in animals, including mitochondria-mutator mice, and in human suggest that oxidative stress and mitochondrial disturbance play an important role in the pathoetiology of ARHL. Mitochondrial DNA (mtDNA) haplogroups are populations with genetically similar traits, and they have been reported to affect the mitochondrial function of oxidative phosphorylation. To gain further insights into the relationships between mitochondrial haplotypes and the susceptibility to cochlear aging, in this study, we aimed to elucidate how the differences in mtDNA haplogroups may affect ARHL development in Japanese general population. We focused on early onset ARHL, as the same mtDNA haplogroup can show either a negative or positive effect on systemic co-morbidities of ARHL that appear later in life. A total of 1167 participants of the Iwaki Health Promotion Project were surveyed in 2014, and 12 major haplotype groups (D4a, D4b, D5, G1, G2, M7a, M7b, A, B4, B5, N9, and F) were selected for the analysis. A total of 698 subjects aged 30 to 65 years were included in the statistical analysis, and the hearing loss group consisted of 112 males (40.3%) and 111 females (26.4%). Multiple logistic regression analysis showed that the male subjects belonging to haplogroup A had a significantly increased risk of hearing loss, whereas the female subjects belonging to haplogroup N9 had a significantly decreased risk of hearing loss. These results suggested that the mtDNA haplogroup may be an indicator for future risk of morbidity associated with ARHL.

Mitochondrial DNA polymorphism and myocardial ischemia: Association of haplogroup H with heart failure

The pathogenesis of atherosclerosis and ischemic heart disease is associated with oxidative stress and mitochondrial dysfunction. Mitochondrial DNA encodes subunits of mitochondrial respiratory chain and is highly polymorphic in human populations. Mitochondrial DNA can be considered a candidate genetic locus for predisposition to cardiovascular diseases.Aim. To analyze the associations of the mitochondrial genome polymorphism and chronic heart failure in ischemic heart disease.Material and Methods. The study included two groups of individuals: patients with a combination of ischemic heart disease and chronic heart failure (n = 175) and a population sample of residents of Tomsk (n = 424). Percentages of patients with chronic heart failure of NYHA classes II, III, and IV were 37%, 50%, and 13%, respectively. All patients underwent echocardiographic examination; body mass index and the lipid fractions in blood serum were determined. The average was 55.4 years in patients and 47.6 years in the population sample. Polymorphism of mtDNA was studied by sequencing the hypervariable segment of D-loop of mtDNA and subsequent classification of mtDNA haplotypes into the known haplogroups. The mtDNA haplogroup frequencies were compared between the samples using the Chi-square test. The associations of genotype with quantitative trait variability were analyzed by variance analysis.Results. Male patients showed a higher frequency of haplogroup H compared to the population (45.86% in patients and 35.4% in population) and a higher total frequency of haplogroup H subgroups except the most frequent subgroup H1 (36.94% and 25.22%, respectively). The values of significance level (p-value) and odds ratio (OR) were determined as follows: p = 0.04; odds ratio OR = 1.55 (95% confidence interval (CI) 1.02–2.34) for haplogroup H as a whole; p = 0.02; OR = 1.74 (95% CI 1.12–2.70) for haplogroup H without subgroup H1. Analysis of quantitative traits revealed the associations of the same genetic marker (mtDNA haplogroup H) with the levels of high-density lipoproteins (p = 0.03) and triglycerides (p = 0.02) in blood serum of men in the population sample.Conclusion. The obtained results suggested that the most frequent European mtDNA haplogroup H may be a risk factor for the complications of ischemic heart disease in men.

mtDNA Haplogroup M5 Associated with Risk of Colorectal Cancer in South India Population

The life on earth is driven by energy, supplied by the tiny organelles of the cell called mitochondria and they are usually stated as the powerhouses of the cell. In population genetics, Mitochondrial DNA (mtDNA) is used extensively to categorize individuals or populations. The mutation sites observed in human mtDNA by comparing with the reference sequence (rCRS) are termed into definite human mtDNA haplogroups. Previous studies showed that mtDNA specific haplogroups and polymorphisms were established to be linked with various human diseases, including cancer in numerous populations. Furthermore, it is also known that several mitochondrial DNA polymorphisms are implicated in enhanced production of Reactive Oxygen Species (ROS) which are known to be an increased risk cause for several cancers, including colorectal cancer in Indian patients. Hence in our study, we made high resolution examination on mtDNA hypervariable region to trace the association of specific mtDNA haplogroup with colorectal cancer in south Indian populations. We report that mtDNA Haplogroup M was observed in 60% of the colorectal cancer patients and around 55% in the studied control samples. Haplogroup M is the most frequent mtDNA cluster found among south Indian populations. We further sub-lineated macro haplogroup M and found sub haplogroups (M8, M7, M6, M5, M3 and M2) in varied frequencies. In particular, we found significant association of haplogroup M5 with colorectal cancer patients (p = 0.026). Haplogroup M5 was observed in 12% of colorectal cancer patients in south Indian patients and in 3.3% of the control populations. These results suggest that individuals with haplogroup M5 may have significant risk to develop colorectal cancer.

To Be a Champion of the 24-h Ultramarathon Race. If Not the Heart ... Mosaic Theory?

This comprehensive case analysis aimed to identify the features enabling a runner to achieve championship in 24-h ultramarathon (UM) races. A 36-year-old, multiple medalist of the World Championships in 24-h running, was assessed before, one and 10 days after a 24-h run. Results of his extensive laboratory and cardiological diagnostics with transthoracic echocardiography (TTE) and a one-time cardiopulmonary exercise test (CPET) were analyzed. After 12 h of running (approximately 130 km), the athlete experienced an increasing pain in the right knee. His baseline clinical data were within the normal range. High physical efficiency in CPET (VO2max 63 mL/kg/min) was similar to the average achieved by other ultramarathoners who had significantly worse results. Thus, we also performed genetic tests and assessed his psychological profile, body composition, and markers of physical and mental stress (serotonin, cortisol, epinephrine, prolactin, testosterone, and luteinizing hormone). The athlete had a mtDNA haplogroup H (HV0a1 subgroup, belonging to the HV cluster), characteristic of athletes with the highest endurance. Psychological studies have shown high and very high intensity of the properties of individual scales of the tools used mental resilience (62–100% depending on the scale), openness to experience (10th sten), coherence (10th sten), positive perfectionism (100%) and overall hope for success score (10th sten). The athlete himself considers the commitment and mental support of his team to be a significant factor of his success. Body composition assessment (%fat 13.9) and the level of stress markers were unremarkable. The tested athlete showed a number of features of the champions of ultramarathon runs, such as: inborn predispositions, mental traits, level of training, and resistance to pain. However, none of these features are reserved exclusively for “champions”. Team support’s participation cannot be underestimated. The factors that guarantee the success of this elite 24-h UM runner go far beyond physiological and psychological explanations. Further studies are needed to identify individual elements of the putative “mosaic theory of being a champion”.

Association of Mitochondrial DNA Genomic Variation With Risk of Pick Disease

ObjectiveTo determine whether stable polymorphisms that define mitochondrial haplogroups in mitochondrial DNA (mtDNA) are associated with Pick disease risk, we genotyped 52 pathologically confirmed cases of Pick disease and 910 neurologically healthy controls and performed case-control association analysis.MethodsFifty-two pathologically confirmed cases of Pick disease from Mayo Clinic Florida (n = 38) and the University of Pennsylvania (n = 14) and 910 neurologically healthy controls collected from Mayo Clinic Florida were genotyped for unique mtDNA haplogroup-defining variants. Mitochondrial haplogroups were determined, and in a case-control analysis, associations of mtDNA haplogroups with risk of Pick disease were evaluated with logistic regression models that were adjusted for age and sex.ResultsNo individual mtDNA haplogroups or superhaplogroups were significantly associated with risk of Pick disease after adjustment for multiple testing (p < 0.0021, considered significant). However, nominally significant (p < 0.05) associations toward an increased risk of Pick disease were observed for mtDNA haplogroup W (5.8% cases vs 1.6% controls, odds ratio [OR] 4.78, p = 0.020) and subhaplogroup H4 (5.8% cases vs 1.2% controls, OR 4.82, p = 0.021).ConclusionOur findings indicate that mtDNA variation is not a disease driver but may influence disease susceptibility. Ongoing genetic assessments in larger cohorts of Pick disease are currently underway.

aYChr-DB: a database of ancient human Y haplogroups

Ancient Y-Chromosomal DNA is an invaluable tool for dating and discerning the origins of migration routes and demographic processes that occurred thousands of years ago. Driven by the adoption of high-throughput sequencing and capture enrichment methods in paleogenomics, the number of published ancient genomes has nearly quadrupled within the last three years (2018–2020). Whereas ancient mtDNA haplogroup repositories are available, no similar resource exists for ancient Y-Chromosomal haplogroups. Here, we present aYChr-DB—a comprehensive collection of 1797 ancient Eurasian human Y-Chromosome haplogroups ranging from 44 930 BC to 1945 AD. We include descriptors of age, location, genomic coverage and associated archaeological cultures. We also produced a visualization of ancient Y haplogroup distribution over time. The aYChr-DB database is a valuable resource for population genomic and paleogenomic studies.

Mitochondrial genome variation in male LHON patients with the m.11778G > A mutation

Leber hereditary optic neuropathy (LHON) is a mitochondrial disorder with symptoms limited to a single tissue, optic nerve, resulting in vision loss. In the majority of cases it is caused by one of three point mutations in mitochondrial DNA (mtDNA) but their presence is not sufficient for disease development, since ~50% of men and ~10% women who carry them are affected. Thus additional modifying factors must exist. In this study, we use next generation sequencing to investigate the role of whole mtDNA variation in male Polish patients with LHON and m.11778G > A, the most frequent LHON mutation. We present a possible association between mtDNA haplogroup K and variants in its background, a combination of m.3480A > G, m.9055G > A, m.11299 T > C and m.14167C > T, and LHON mutation. These variants may have a negative effect on m.11778G > A increasing its penetrance and the risk of LHON in the Polish population. Surprisingly, we did not observe associations previously reported for m.11778G > A and LHON in European populations, particularly for haplogroup J as a risk factor, implying that mtDNA variation is much more complex. Our results indicate possible contribution of novel combination of mtDNA genetic factors to the LHON phenotype.

Relationship between mitochondrial DNA haplogroup and litter size in the pig

Mitochondrial DNA (mtDNA) has been widely associated with complex traits in farm animals. The present study evaluated the effects of mtDNA on litter size in pigs. Mitogenome sequencing of 1017 sows distinguished 232 variations, including 229 single nucleotide polymorphisms and three indels, which constituted 11 haplotypes and further clustered into two haplogroups that differed significantly (P&lt;0.05) in litter size. In order to explain the associations between the effect of haplogroup on litter size and different maternal origins, extant mitogenome sequences were used for phylogenetic or principal component analyses. The results of these analyses led to the identification of two groups, representing Chinese and European origins. The haplotypes corresponding to high litter size were all in the Chinese cluster, whereas haplotypes corresponding to low litter size were all in the European cluster. The results of this study suggest that the effect of haplogroup on litter size in the pig could be caused by diverse maternal origins, and that mtDNA haplogroup may be a marker for genetic selection for pig litter size.

Comparative study between Helicobacter pylori and host human genetics in the Dominican Republic

Background Helicobacter pylori, a bacterium that infects the human stomach, has high genetic diversity. Because its evolution is parallel to human, H. pylori is used as a tool to trace human migration. However, there are few studies about the relationship between phylogeography of H. pylori and its host human. Methods We examined both H. pylori DNA and the host mitochondrial DNA and Y-chromosome DNA obtained from a total 119 patients in the Dominican Republic, where human demography consists of various ancestries. DNA extracted from cultured H. pylori were analyzed by multi locus sequence typing. Mitochondrial DNA and Y-chromosome DNA were evaluated by haplogroup analyses. Results H. pylori strains were divided into 2 populations; 68 strains with African group (hpAfrica1) and 51 strains with European group (hpEurope). In Y-chromosomal haplogroup, European origin was dominant, whereas African origin was dominant both in H. pylori and in mtDNA haplogroup. These results supported the hypothesis that mother-to-child infection is predominant in H. pylori infection. The Amerindian type of mtDNA haplogroup was observed in 11.8% of the patients; however, Amerindian type (hspAmerind) of H. pylori was not observed. Although subpopulation type of most hpAfrica1 strains in Central America and South America were hybrid (hspWAfrica/hpEurope), most Dominican Republic hpAfrica1 strains were similar to those of African continent. Conclusions Genetic features of H. pylori, mtDNA, and Y haplogroups reflect the history of colonial migration and slave trade in the Dominican Republic. Discrepancy between H. pylori and the host human genotypes support the hypothesis that adaptability of hspAmerind H. pylori strains are weaker than hpEurope strains. H. pylori strains in the Dominican Republic seem to contain larger proportion of African ancestry compared to other American continent strains.