Proportion Of Genotypes Research Articles

What in Earth? Analyses of Canadian soil populations of Aspergillus fumigatus

Aspergillus fumigatus is a globally distributed mold and a major cause of opportunistic infections in humans. Because most infections are from environmental exposure, it’s critical to understand environmental populations of A. fumigatus. Soil is a major ecological niche for A. fumigatus. Here we analyzed 748 soil isolates from 21 locations in six provinces and one territory in Canada. All isolates were genotyped using nine microsatellite markers. Due to small sample size and/or close proximities for some local samples, these isolates were grouped into 16 local geographic and ecological populations. Our results indicated high allelic and genotypic diversities within most local and provincial populations. Interestingly, low but statistically significant genetic differentiations were found among geographic populations within Canada, with relatively similar proportions of strains and genotypes belonging to two large genetic clusters. In Hamilton, Ontario and Vancouver, BC, where two and three ecological populations were analyzed respectively, we found limited genetic difference among them. Most local and provincial populations showed evidence of both clonality and recombination, with no population showing random recombination. Of the 748 soil isolates analyzed here, two were resistant to triazole antifungals. We discuss the implications of our results to the evolution and epidemiology of A. fumigatus.

Genetic, breeding and environmental parameters for yellow sugarcane aphid (Sipha flava) damage in advanced South African sugarcane breeding populations

Yellow sugarcane aphid (YSA), a native pest of temperate and subtropical regions in North America, has spread to many regions of the world including KwaZulu-Natal and Mpumalanga sugarcane growing regions of South Africa. Cultivar differences to YSA damage have been observed in Mpumalanga where high infestation levels occur. The objectives of this study were to determine genetic, breeding, and environmental parameters for YSA damage and implications on breeding for resistance. Data for YSA damage were collected from 12 genotype populations planted in Mpumalanga. There were significant (p < 0.0001) genotype effects indicating genetic variability. Significant (p < 0.01) environment effects showed that YSA damage in February was significantly (p < 0.05) higher than in December. The significant (p < 0.01) genotype by environment interaction indicated February as the best month to screen for YSA. Higher broad sense heritability (> 0.70) suggests selecting resistant genotypes would be effective. Data collected in February produced higher broad sense heritability (> 0.80) than in December (< 0.70) suggesting February as the preferred month to score for damage. The proportion of resistant genotypes was 16.5% (range 2–34%), indicating the presence of resistant in South African advanced genotype populations. Evaluation of released cultivars showed N36, N49 and N71 are resistant while N57 and N73 are susceptible.

Strongly deleterious mutations influence reproductive output and longevity in an endangered population

Inbreeding depression has been documented in various fitness traits in a wide range of species and taxa, however, the mutational basis is not yet well understood. We investigate how putatively deleterious variation influences fitness and is shaped by individual ancestry by re-sequencing complete genomes of 37 individuals in a natural arctic fox (Vulpes lagopus) population subjected to both inbreeding depression and genetic rescue. We find that individuals with high proportion of homozygous loss of function genotypes (LoFs), which are predicted to exert a strong effect on fitness, generally have lower lifetime reproductive success and live shorter lives compared with individuals with lower proportion of LoFs. We also find that juvenile survival is negatively associated with the proportion of homozygous missense genotypes and positively associated with genome wide heterozygosity. Our results demonstrate that homozygosity of strongly and moderately deleterious mutations can be an important cause of trait specific inbreeding depression in wild populations, and mark an important step towards making more informed decisions using applied conservation genetics.

Artificial Seed Bioassay for Assessing Genotypic Resistance of Pigeon Pea to Callosobruchus chinensis

Pulse beetle, Callosobruchus chinensis is a significant pest of stored legumes, particularly pigeon pea (Cajanus cajan), causing substantial damage and economic losses. This study investigates the resistance of various pigeonpea genotypes to C. chinensis using artificial seeds in a controlled single-choice bioassay. Artificial seeds in bioassays help provide consistent conditions for studying pigeon pea resistance to pests like C. chinensis. Unlike natural seeds, which can vary in traits like size, texture, and composition, artificial seeds ensure that any observed resistance is due to the plant's genetics, not differences in the seeds themselves. Despite using seeds with different proportions of resistant and susceptible genotypes, no significant differences were observed in the beetle oviposition behavior. The findings suggest that factors other than nutritional content may influence bruchid resistance, emphasize the need for further research into specific phytochemicals responsible for resistance. This work has important implications for the development of more resistant pigeon pea cultivars.

Transport of topological defects in a biphasic mixture of active and passive nematic fluids

Collectively moving cellular systems often contain a proportion of dead cells or non-motile genotypes. When mixed, nematically aligning motile and non-motile agents are known to segregate spontaneously. However, the role that topological defects and active stresses play in shaping the distribution of the two phases remains unresolved. In this study, we investigate the behaviour of a two-dimensional binary mixture of active and passive nematic fluids to understand how topological defects are transported between the two phases and, ultimately, how this leads to the segregation of topological charges. When the activity of the motile phase is large, and the tension at the interface of motile and non-motile phases is weak, we find that the active phase tends to accumulate +1/2 defects and expel −1/2 defects so that the motile phase develops a net positive charge. Conversely, when the activity of the motile phase is comparatively small and interfacial tension is strong, the opposite occurs so that the active phase develops a net negative charge. We then use these simulations to develop a physical intuition of the underlying processes that drive the charge segregation. Lastly, we quantify the sensitivity of this process on the other model parameters, by exploring the effect that anchoring strength, orientational elasticity, friction, and volume fraction of the motile phase have on topological charge segregation. As +1/2 and −1/2 defects have very different effects on interface morphology and fluid transport, this study offers new insights into the spontaneous pattern formation that occurs when motile and non-motile cells interact.

Clinical and molecular findings in children with retinitis pigmentosa

ABSTRACT Purpose To study the clinical and genetic features of a cohort of RP children. Methods We identified 46 RP patients with pathogenic or likely pathogenic mutations among 96 patients with a clinical diagnosis of retinitis pigmentosa. All of the patients underwent comprehensive clinical examinations and genetic testing. A retrospective study was conducted on 46 children with retinitis pigmentosa. The genetic and clinical characteristics of children with different genotypes were analyzed. Results Among the 46 children, 13 inherited X-linked gene mutations, including 9 RPGR and 4 RP2 mutations. There were 10 cases of autosomal dominant genes and 23 cases of autosomal recessive genes. XLRP accounted for a larger proportion of children, as observed in previous studies on RP. We found that RPGR genes were the most commonly mutated genes in RP children. The most frequently mutated gene was RPGR (9.3%), followed by RP2 (4.2%) and RPE65 (4.2%). Forty-six patients had mutations in 21 different genes, 19 of which were novel mutations. Most children with XLRP have a high degree of myopia, poor vision, and severe clinical symptoms. Frameshift mutations were more common in XLRP, followed by nonsense mutations. The onset of XLRP is relatively serious since childhood. Most children with ADRP have relatively good visual acuity and mild clinical symptoms, and missense mutations are common. The clinical manifestations of ARRP in children are more severe than those of ADRP in children but milder than those of XLRP in children, and missense mutations are common. The manifestations of RPE65 mutations are also severe and appear early. Conclusions Our results revealed that XLRP gene mutations were more common in children than in adults, as observed in previous studies on RP. The proportion of RP children with ADRP is relatively small. The new findings in our study polished the spectrum of novel mutations and the proportions of different genotypes in pediatric patients. The onset of XLRP occurred earlier. The genes with a high incidence in children were all relatively severe gene types of RP. This comprehensive database may provide essential information regarding the initial stage of RP.

Wastewater and clinical surveillance of respiratory viral pathogens on a university campus

Areas of dense population congregation are prone to experience respiratory virus outbreaks. We monitored wastewater and clinic patients for the presence of respiratory viruses on a large, public university campus. Campus sewer systems were monitored in 16 locations for the presence of viruses using next generation sequencing over 22 weeks in 2023. During this period, we detected a surge in human adenovirus (HAdV) levels in wastewater. Hence, we initiated clinical surveillance at an on-campus clinic from patients presenting with acute respiratory infection. From whole genome sequencing of 123 throat and/or nasal swabs collected, we identified an outbreak of HAdV, specifically of HAdV-E4 and HAdV-B7 genotypes overlapping in time. The temporal dynamics and proportions of HAdV genotypes found in wastewater were corroborated in clinical infections. We tracked specific single nucleotide polymorphisms (SNPs) found in clinical virus sequences and showed that they arose in wastewater signals concordant with the time of clinical presentation, linking community transmission of HAdV to the outbreak. This study demonstrates how wastewater-based epidemiology can be integrated with surveillance at ambulatory healthcare settings to monitor areas prone to respiratory virus outbreaks and provide public health guidance.

Measuring local genetic variation in permethrin-resistant head lice (Phthiraptera: Pediculidae) from Buenos Aires, Argentina.

The cosmopolitan ectoparasite human head louse, Pediculus humanus capitis (De Geer)(Phthiraptera:Pediculidae), affects mostly school-aged children, with infestations reported every year mainly due to louse resistance to pyrethroids. One of the main resistance mechanisms of pyrethroids is the target site insensitivity (kdr), which is caused by single-nucleotide point mutations (SNPs) located in the voltage-sensitive sodium channel gene. In this study, we analyzed individual head lice toxicologically via the description of their susceptibility profile to permethrin and genetically through the genotypification of their kdr alleles as well as nuclear microsatellite loci. Lice were collected from 4 schools in the city of Buenos Aires, Argentina. The resistance ratios varied from 33.3% to 71.4%, with a frequency of the T917I kdr mutation of 87.31% and with 83.6% of the head lice being homozygous resistant to pyrethroids. Microsatellite data indicated that all the louse school populations had genotype proportions that deviated from Hardy-Weinberg expectations, with FIS > 0 reflecting a deficit of heterozygotes. Bottleneck analysis suggested that all louse school populations underwent a recent reduction in population sizes, while 3 of the 4 schools had gene flow values around 1, indicating ongoing gene flow among those schools. Our study suggests that school louse populations in the city of Buenos Aires may form a metapopulation, where each school represents a small population that undergoes extinction and recolonization processes under strong permethrin selection. This is the first multilevel analysis integrating toxicological, kdr-genotyping, and microsatellite data in human louse populations.

Identification of High Erucic Acid Brassica carinata Genotypes through Multi-Trait Stability Index

Brassica carinata is an important and native oilseed crop in Ethiopia. The seed oil from B.carinata attracts global attention for its various industrial applications, mainly due to its high erucic acid levels and its superior agronomic traits. Since the demand for high erucic acid from oilseed brassica has been increasing in the world market due to its wider applications in bio-industries, the breeding target of B. carinata has recently been focused on enhancing its erucic acid. Several high erucic acid B. carinata genotypes have been screened from the pre-breeding activities. Such genotypes, however, need to be tested for their stable performance, for their erucic acid level, and other desirable traits under different environments. The aim of this study was to identify high erucic acid B. carinata genotypes with stable performance in multiple desirable traits. Thirty-two B. carinata genotypes were grown in a randomized complete block design with three replications at three locations for two years. The genotypes were evaluated for nine desirable traits related to seed oil quality (erucic acid and oil content), seed yield, and other agronomic traits. The results showed that the proportion of genotype by environment interaction (GEI) was clearly observed in erucic acid, which led to a stability and mean performance analysis for selecting the most stable and best-performing genotypes for the desired traits. For such an analysis, we used the multi-trait stability index (MTSI) along with the weighted average of absolute score BLUPs (WAASB). As revealed from the MTSI, five genotypes (G13, G18, G10, G22 and G5) were identified as the most stable in erucic acid, oil content, seed yield, and other agronomic traits. The selected genotypes showed on average 45.7% erucic acid, 3185 kg ha−1 seed yield and 45.1% oil content with 4.3%, 25.8% and 6.9% positive selection gain, respectively. The negative selection gain of phenological traits and the plant height of the selected genotypes revealed their early maturity and their lower probability of being affected by lodging. Our findings demonstrated MTSI can be used to select high erucic acid B. carinata with a set of desirable traits, which would facilitate breeding efforts in developing novel and high erucic acid B. carinata varieties. Our results also showed that MTSI is an effective tool for selecting genotypes across different environments due to its unique ability to select multiple traits simultaneously.

Cluster approach to identifying the 5-year prognosis of patients with chronic heart failure of ischemic etiology

BACKGROUND: The phenotypic and pathophysiological heterogeneity of patients with chronic heart failure increases the interest of researchers in grouping according to similar clinical and genetic characteristics based on cluster analysis. AIM: To identify phenotypic subgroups in a multivariate cohort of patients with chronic heart failure secondary to coronary artery disease using uncontrolled cluster analysis of clinical, instrumental and genetic components. MATERIAL AND METHODS: 470 patients with chronic heart failure of functional class I–IV, stable course, ischemic etiology of both sexes at the age of 66.4±10.4 years were examined. A clinical study was conducted, genotyping single nucleotide polymorphisms rs10927875 of the ZBTB17 gene, rs247616 of the CETP gene, rs1143634 of the IL-1β gene, rs1800629 of the TNF gene, rs1800795 of the IL-6 gene was carried out, and patient outcomes were assessed for 5 years. Quantitative data were presented as mean and standard deviation or median and interquartile range; categorical — as frequencies and percentages. Categorical intergroup differences were tested using the χ2 test, and quantitative differences were tested using the Student/Mann–Whitney test. Hierarchical clustering was carried out according to 44 demographic, clinical, genetic variables, time to event was analyzed by the Kaplan–Meier method, risk ratio — by Cox regression. Statistical processing was carried out in the R4.3.1 program. RESULTS: Two clusters of patients with heart failure were identified. Cluster 1 (66%) included older patients of both sexes, predominantly functional class III–IV chronic heart failure, with enlarged heart chambers, reduced left ventricular ejection fraction, higher heart rate, atrial fibrillation and left ventricular hypertrophy. In this cluster, more carriers of the GG genotype of the rs1800795 polymorphism of the IL-6 gene (p 0.001) and the CT genotype of the rs247616 polymorphism of the CETP gene (p=0.014) were identified. Cluster 2 (34%) was represented predominantly by younger women, with a higher metabolic index, a history of myocardial infarction and coronary intervention, smokers, and a larger proportion of the TT genotype of the rs247616 polymorphism of the CETP gene (p=0.029). CONCLUSION: 2 clusters of patients with chronic heart failure, characterized by a different set of 44 variables that determine the risk of death from all causes, were identified.

Genetic Polymorphism of Interleukin-6 in Asymptomatic and ICU-Admitted COVID-19 Patients in Sulaymaniyah Province, Kurdistan Region of Iraq.

Background: The global pandemic of Coronavirus Disease 2019 (COVID-19) has resulted in significant fatality rates. Clinical outcomes for affected individuals range from being asymptomatic to severe illnesses requiring intensive care unit (ICU) admission. Among the various factors contributing to the variation in clinical outcomes, host genetics play a prominent role. Interleukin-6 (IL6), a key player in immune responses, has been identified as having a crucial impact on viral infections, including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Specifically, certain variations known as single nucleotide polymorphisms (SNPs) in the IL6 promoter region have been found to significantly influence IL6 expression and the severity of viral infections. Materials and Methods: To explore the relationship between these genetic variations and COVID-19 in asymptomatic and ICU-admitted Kurdish patients, genetic sequencing was performed to determine the genotypes of nine IL6 SNPs. Results: The study findings revealed that although the proportion of the GG genotype of rs1800795 was slightly higher in asymptomatic COVID-19 cases, the difference was not statistically significant (chi2 = 2.666, p = 0.236). Notably, Kurdish patients displayed a uniform genetic makeup (monomorphic) for the dominant alleles of rs2069830 (C), rs142759801 (C), rs2069857 (C), rs2069829 (G), rs2234683 (G), rs13447446 (T), rs527770772 (C), and rs13447445 (C). Furthermore, patients carrying the haplotype GCGGCTCCC were found to have a 0.481-fold higher likelihood of being asymptomatic with COVID-19 (p = 0.016, OR = 0.481). Conclusions: This study demonstrates that the rs1800795 SNP is not statistically associated with COVID-19 at the genotype level. However, the presence of the dominant G allele of rs1800795 in the haplotype was found to be statistically associated with asymptomatic COVID-19 patients.

A knock-in allele of Hand2 expressing Dre recombinase.

HAND2 is a basic helix-loop-helix transcription factor with diverse functions during development. To facilitate the investigation of genetic and functional diversity among Hand2-expressing cells in the mouse, we have generated Hand2Dre, a knock-in allele expressing Dre recombinase. To avoid disrupting Hand2 function, the Dre cDNA is inserted at the 3' end of the Hand2 coding sequence following a viral 2A peptide. Hand2Dre homozygotes can therefore be used in complex crosses to increase the proportion of useful genotypes among offspring. Dre expression in mid-gestation Hand2Dre embryos is indistinguishable from wild-type Hand2 expression, and HandDre efficiently recombines rox target sites in vivo. In combination with existing Cre and Flp mouse lines, Hand2Dre will therefore extend the ability to perform genetic intersectional labeling, fate mapping, and functional manipulation of subpopulations of cells characterized by developmental expression of Hand2.

Genetic diversity among the present Japanese population: evidence from genotyping of human cell lines established in Japan

Japan is often assumed to have a highly homogeneous ethnic population, because it is an island country. This is evident in human cell lines collected from cell banks; however, these genotypes have not been thoroughly characterized. To examine the population genotypes of human cell lines established in Japan, we conducted SNP genotyping on 57 noncancerous cell lines and 43 lung cancer cell lines. Analysis of biogeographic ancestry revealed that 58 cell lines had non-admixed Japanese genotypes, 21 cell lines had an admixture of Japanese and East Asian genotypes, and the remaining 21 cell lines had East Asian genotypes. The proportion of non-admixed Japanese genotypes was similar between lung cancer and noncancerous cell lines, suggesting that patients in Japan may not exclusively have Japanese genotypes. This could influence the incidence of inherited diseases and should be taken into account in personalized medicine tailored to genetic background. The genetic makeup of the present-day Japanese population cannot be fully explained by the ancestral Jomon and Yayoi lineages. Instead, it is necessary to consider a certain level of genetic admixture between Japanese and neighboring Asian populations. Our study revealed genetic variation among human cell lines derived from Japanese individuals, reflecting the diversity present within the Japanese population.

Sequential Bayesian approach for genetic diversity analysis of the piracanjuba fish (Brycon orbignyanus)

In the sequential Bayesian approach, the sample size is not fixed before the experiment; it is determined based on the observations made. The procedure concludes when there is enough information to estimate the parameters, according to a stopping criterion. A parameter of interest in population genetics is the proportion obtained from the allele frequency at one or more loci to verify Hardy-Weinberg equilibrium (HWE). The objective of this study was to assess the occurrence of HWE in a population of piracanjuba fish (Brycon orbignyanus) by estimating the allele proportion and expected genotype proportions using a sequential Bayesian approach. Additionally, a comparison was made with frequentist and Bayesian approaches. Initially, genotypic profiles were analyzed at a microsatellite DNA locus, Bh6, in 49 fish, to determine the frequency of observed alleles and genotypes at the UFSJ Genetic Resources Laboratory. Seven allele classes were observed; thus, under the assumption of sampling independence, the likelihood is multinomial. The estimation of allele and genotype proportions was then carried out using frequentist, Bayesian, and sequential Bayesian approaches. A uniform prior and a cost of 10–3 were considered. The estimates from the three approaches were compared, and it was concluded that the sequential approach proved effective, utilizing only 55.1% of the available data, thereby reducing the sample size and optimizing the procedure. Using a chi-square test at a 5% probability level, it was concluded that the studied sample is in Hardy-Weinberg equilibrium (p-value: 0.9800245).

How do seasonal temperature variations influence interplay between toxic and non-toxic cyanobacterial blooms? Evidence from modeling and experimental data

Summer cyanobacterial blooms exhibit a dynamic interplay between toxic and non-toxic genotypes, significantly influencing the cyanotoxin levels within a lake. The challenge lies in accurately predicting these toxin concentrations due to the significant temporal fluctuations in the proportions of toxic and non-toxic genotypes. Typically, the toxic genotypes dominate during the early and late summer periods, while the non-toxic variants prevail in mid-summer. To dissect this phenomenon, we propose a model that accounts for the competitive interaction between toxic and non-toxic genotypes, as well as seasonal temperature variations. Our numerical simulations suggest that the optimal temperature of the toxic genotypes is lower than that of the optimal temperatures of the non-toxic counterparts. This difference of optimal temperature may potentially contribute to explain the dominance of toxic genotypes at the early and late summer periods, situation often observed in the field. Experimental data from the laboratory align qualitatively with our simulation results, enabling a better understanding of complex interplays between toxic and non-toxic cyanobacteria.

Distribution patterns of molecular markers of antimalarial drug resistance in Plasmodium falciparum isolates on the Thai-Myanmar border during the periods of 1993–1998 and 2002–2008

BackgroundPolymorphisms of Plasmodium falciparum chloroquine resistance transporter (pfcrt), Plasmodium falciparum multi-drug resistance 1 (pfmdr1) and Plasmodium falciparum kelch 13-propeller (pfk13) genes are accepted as valid molecular markers of quinoline antimalarials and artemisinins. This study investigated the distribution patterns of these genes in P. falciparum isolates from the areas along the Thai-Myanmar border during the two different periods of antimalarial usage in Thailand.ResultsPolymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were used to detect pfcrt mutations at codons 76, 220, 271, 326, 356, and 371 as well as pfmdr1 mutation at codon 86. The prevalence of pfcrt mutations was markedly high (96.4–99.7%) in samples collected during both periods. The proportions of mutant genotypes (number of mutant/total isolate) at codons 76, 220, 271, 326, 356 and 371 in the isolates collected during 1993–1998 (period 1) compared with 2002–2008 (period 2) were 97.9% (137/140) vs. 97.1% (401/413), 97.9% (140/143) vs. 98.8% (171/173), 97.2% (139/143) vs. 97.1% (333/343), 98.6% (140/142) vs. 99.7% (385/386), 96.4% (134/139) vs. 98.2% (378/385) and 97.8% (136/139) vs. 98.9% (375/379), respectively. Most isolates carried pfmdr1 wild-type at codon 86, with a significant difference in proportions genotypes (number of wild type/total sample) in samples collected during period 1 [92.9% (130/140)] compared with period 2 [96.9% (379/391)]. Investigation of pfmdr1 copy number was performed by real-time PCR. The proportions of isolates carried 1, 2, 3 and 4 or more than 4 copies of pfmdr1 (number of isolates carried correspondent copy number/total isolate) were significantly different between the two sample collecting periods (65.7% (90/137) vs. 87.8% (390/444), 18.2% (25/137) vs. 6.3%(28/444), 5.1% (7/137) vs. 1.4% (6/444) and 11.0% (15/137) vs. 4.5% (20/444), for period 1 vs. period 2, respectively). No pfk13 mutation was detected by nested PCR and nucleotide sequencing in all samples with successful analysis (n = 68).ConclusionsThe persistence of pfcrt mutations and pfmdr1 wild-types at codon 86, along with gene amplification in P. falciparum, contributes to the continued resistance of chloroquine and mefloquine in P. falciparum isolates in the study area. Regular surveillance of antimalarial drug resistance in P. falciparum, incorporating relevant molecular markers and treatment efficacy assessments, should be conducted.

Role of polymorphism in vitamin D receptor gene on diabetic foot ulcer: A systematic review and meta-analysis

Context: Once vitamin D is converted to its active form, the molecule binds to its receptor (VDR) and performs its function as a transcription factor in modulating immune response, inflammation cascade, and insulin signaling. Among diabetic individuals, these activities are thought to be correlated with foot ulceration. Gene polymorphisms could change the function of VDR, thereby affecting the development of foot ulceration among individuals with diabetes. Aims: To construct evidence on the role of VDR gene variants or single nucleotide polymorphisms (SNPs) on diabetic foot ulcers. Methods: Records reporting the distribution of genotypes and/or alleles among diabetic foot ulcer (DFU) patients and published until 10 March 2023 were retrieved from 12 major databases using predetermined keywords. The original research articles included in the study were assessed for reporting quality using the Newcastle Ottawa Scale. The quality of genotypic and allelic data was appraised by Hardy-Weinberg equilibrium (HWE). A quantitative analysis-based fixed-effects model was performed to estimate the proportion of genotype and allele frequencies among DFU patients. Results: Three studies were included in the systematic review reporting the FokI (rs2228570), TaqI (rs731236), BsmI (rs1544410), and ApaI (rs7975232) SNPs. Based on pooled estimates, among DFU patients CC, CT, and TT genotypes of VDR FokI SNPs had a prevalence of 45%, 43%, and 12%, respectively, without significant heterogeneity found in the reported data (p-Het&lt;0.001; I2&gt;0%). ApaI and FokI were associated with DFU, while no association in all genotypic and allelic models was found between TaqI or BsmI and DFU. CC genotype of BsmI and T allele of FokI was associated with oxidative stress (one of the underlying factors in DFU). Conclusions: Certain genotypes and alleles of FokI and ApaI SNPs could act as the risk factor for foot ulceration among diabetic individuals. More high-quality studies are still needed to draw solid conclusions on the role of VDR SNPs among DFU patients.

Prevalence of single-nucleotide variants in twenty-five pharmacogenes from a Cuban sample cohort.

The Cuban population is genetically diverse, and information on the prevalence of genetic variants is still limited. As complex admixture processes have occurred, we hypothesized that the frequency of pharmacogenetic variants and drug responses may vary within the country. The aims of the study were to describe the frequency distribution of 43 single-nucleotide variants (SNVs) from 25 genes of pharmacogenetic interest within the Cuba population and in relation to other populations, while taking into consideration some descriptive variables such as place of birth and skin color. SNVs were analyzed in 357 unrelated healthy Cuban volunteers. Genotype, allele frequencies, and ancestry proportions were determined, and the pairwise fixation index (FST ) was evaluated. Hardy-Weinberg equilibrium (HWE) deviations in six loci (rs11572103, rs2740574, rs776746, rs3025039, rs861539, and rs1762429) were identified. Minor allele frequencies (MAFs) ranged from 0.00 to 0.15 for variants in genes encoding xenobiotic metabolizing enzymes. They also ranged from 0.01 to 0.21 for variants in DNA repair, growth factors, methyltransferase, and methyl-binding proteins, while they ranged from 0.04 to 0.27 for variants in the O-6-methylguanine-DNA methyltransferase enzyme. Moderate genetic divergence was observed upon comparison to Africans (FST = 0.071 and SD 0.079), with 19 markers exhibiting moderate-to-large genetic differentiation. The average European, African, and Amerindian ancestry proportions were 67.8%, 27.2%, and 5.3%, respectively. Ancestry proportions differed by skin color and birthplace for both African and European components, with the exception of the European component, which showed no significant difference between individuals from Western and Eastern regions. Meanwhile, the statistical significance varied in comparisons by skin color and birthplace within the Amerindian component. Low genetic divergence was observed across geographical regions. We identified 12 variants showing moderate-to-large differentiation between White/Black individuals. Altogether, our results may support national strategies for the introduction of pharmacogenetic tools in clinical practice, contributing to the development of precision medicine in Cuba.

Hepatitis B virus genotype surveillance in Canadian blood donors and a referred patient population, 2016-2021.

Hepatitis B virus (HBV) genotypes (A-H) have a distinct geographic distribution and are highly associated with the country of birth. Canada has experienced increased immigration over the past decade, primarily from regions where HBV is endemic. This study investigated the proportions and trends of HBV genotypes within blood donor and clinical populations of Canada over the period 2016-2021. Study samples involved two cohorts: (1) Canadian blood donors (n = 246) deferred from donation due to HBV test positivity and (2) chronic HBV patients from across Canada (clinically referred population, n = 3539). Plasma or serum was extracted, and the surface antigen and/or polymerase-coding region was amplified and sequenced to determine genotype by phylogenetic analysis. Six (A-E, G) and eight (A-H) HBV genotypes were detected among deferred blood donors and the clinically referred population, respectively. Differences in HBV genotype proportions between the two cohorts were observed across Canada. Males comprised most of the referred population among genotypes A-E (p < 0.0001), except for genotypes B and C. The median age was younger among blood donors (36 years [range 17-72]) compared with the referred population (41 years [range 0-99]). Distinct trends of increasing (E, referred; B, blood donor) and decreasing genotype prevalence were observed over the study period. HBV genotypes in Canada are highly diverse, suggesting a large immigrant population. Observed trends in genotype prevalence and proportional differences among cohorts imply shifts among the HBV-infected population of Canada, which warrants continued surveillance.

Does FOXO3 longevity genotype explain the conflicting data on late‐life hypertension and risk of Alzheimer’s disease?

AbstractBackgroundThe association of late‐life hypertension (LHTN) with Alzheimer’s disease (AD) remains controversial. We hypothesize that FOXO3 longevity‐associated genotype modulates the association between LHTN and incident AD.MethodSubjects were 2,688 American men of Japanese ancestry (baseline age: 77.0 ± 4.1 years, range 71‐93 years) from the Kuakini Honolulu Heart Program. Status was known for FOXO3 rs2802292 genotype, LHTN at baseline, and diagnosis of incident dementia over 21 years follow‐up. Association of FOXO3 genotype with LHTN and incident all‐cause dementia, vascular dementia (VD) and Alzheimer’s disease was assessed using Cox regression.ResultDuring the follow‐up, 725 men were diagnosed with all‐cause dementia, 513 with AD and 104 with VD. A multivariable Cox model, adjusting for age, education, APOE‐ε4 and cardiovascular risk factors, showed LHTN increased VD risk (HR = 1.71, 95%CI = 1.08–2.71, p = 0.022), but not AD risk. We found no significant protective effect of FOXO3 longevity genotype, nor of LHTN, on all‐cause dementia and AD at the population level. However, in a full Cox model adjusting for age, education, APOE‐ε4 and other cardiovascular risk factors, there was a significant interaction effect of LHTN and FOXO3 longevity genotype on incident AD (ß = –0.52, p = 0.0061). In men with FOXO3 rs2802292 longevity genotype (TG/GG), LHTN showed protection against AD (HR = 0.72; 95% CI = 0.55–0.95, p = 0.021). In men with FOXO3 rs2802292 non‐longevity genotype (TT), LHTN had no protective effect (HR = 1.16; 95% CI = 0.90‐1.51, p = 0.25).DiscussionSince the effect of LHTN on AD incidence differed according to FOXO3 genotype, the overall effect, namely, a weighted average effect of LHTN on AD across different FOXO3 genotypes, would be moving towards the null (i.e., HR = 1). This would explain why most studies have found no significant association between LHTN and AD. One exception is the Ibadan study, in which all participants were African American. African Americans have the highest proportion (94%) of FOXO3 rs2802292 longevity genotype (TG/GG) in all races, and the strongest effect of LHTN in protecting against AD (RR = 0.33).ConclusionThis longitudinal study found that FOXO3 genotype modulates the effect of late‐life hypertension on incident AD, thus explaining the conflicting data on late‐life hypertension and Alzheimer’s disease.