Association of vitamin D receptor gene polymorphisms with type 2 diabetes mellitus in Taif population: a case-control study / Associação de polimorfismos do gene do receptor de vitamina D com diabetes mellitus tipo 2 na população Taif: um estudo de caso-controle

Abstract Several reasons may underlie the dramatic increase in type2 diabetes mellitus. One of these reasons is the genetic basis and variations. Vitamin D receptor polymorphisms are associated with different diseases such as rheumatoid arthritis and diabetes. The aim of this study is to investigate the possible association of two identified mutations ApaI (rs7975232) and TaqI (rs731236). Eighty-nine healthy individuals and Fifty-six Type 2 Diabetic (T2D) patients were investigated using RFLP technique for genotyping and haplotyping as well. The distribution of Apal genotypes was not statistically significant among the control (P=0.65) as well as for diabetic patients (P=0.58). For Taql allele frequencies of T allele was 0.61 where of G allele was 0.39. The frequency distribution of Taql genotypes was not statistically significant among the control (P=0.26) as well as diabetic patients (P=0.17). Relative risk of the allele T of Apa1 gene is 1.28 and the odds ratio of the same allele is 1.53, while both estimates were < 1.0 of the allele G. Similarly, with the Taq1 gene the relative risk and the odds ratio values for the allele T are 1.09 and 1.27 respectively and both estimates of the allele C were 0.86 for the relative risk and 0.79 for the odds ratio. The pairwise linkage disequilibrium between the two SNPs Taq1/apa1 was statistically significant in control group (D = 0.218, D' = 0.925 and P value < 0.001) and similar data in diabetic groups (D = 0.2, D' = 0.875 and P value < 0.001). These data suggest that the T allele of both genes Apa1 and Taq1 is associated with the increased risk of type 2 diabetes. We think that we need a larger number of volunteers to reach a more accurate conclusion.

Resumo Várias razões podem estar subjacentes ao aumento dramático da diabetes mellitus tipo 2. Um desses motivos é a base genética e variações. Os polimorfismos do receptor da vitamina D estão associados a diferentes doenças, como artrite reumatoide e diabetes. O objetivo deste estudo é investigar a possível associação de duas mutações identificadas ApaI (rs7975232) e TaqI (rs731236). Oitenta e nove indivíduos saudáveis ​​e 56 pacientes com diabetes tipo 2 (T2D) foram investigados usando a técnica RFLP para genotipagem e haplotipagem também. A distribuição dos genótipos Apal não foi estatisticamente significativa entre o controle (P = 0,65), bem como para os pacientes diabéticos (P = 0,58). Para as frequências do alelo Taql, o alelo T foi de 0,61, onde o alelo G foi de 0,39. A distribuição de frequência dos genótipos Taql não foi estatisticamente significativa entre o controle (P = 0,26), bem como os pacientes diabéticos (P = 0,17). O risco relativo do alelo T do gene Apa1 é 1,28 e a razão de chances do mesmo alelo é 1,53, enquanto ambas as estimativas foram < 1,0 do alelo G. Da mesma forma, com o gene Taq1, os valores de risco relativo e razão de chances para o alelo T são 1,09 e 1,27, respectivamente, e ambas as estimativas do alelo C foram de 0,86 para o risco relativo e 0,79 para o odds ratio. O desequilíbrio de ligação par a par entre os dois SNPs Taq1 / apa1 foi estatisticamente significativo no grupo de controle (D = 0,218, D' = 0,925 e valor P < 0,001) e dados semelhantes em grupos diabéticos (D = 0,2, D' = 0,875 e valor P < 0,001). Esses dados sugerem que o alelo T de ambos os genes Apa1 e Taq1 está associado ao aumento do risco de diabetes tipo 2. Achamos que precisamos de um número maior de voluntários para chegar a uma conclusão mais precisa.

Increased yield performance of mutation induced Soybean genotypes at varied agro-ecological conditions / Aumento no desempenho de rendimento de genótipos de soja induzidos por mutação em condições agroecológicas variadas

Abstract In soybean breeding program, continuous selection pressure on traits response to yield created a genetic bottleneck for improvements of soybean through hybridization breeding technique. Therefore an initiative was taken to developed high yielding soybean variety applying mutation breeding techniques at Plant Breeding Division, Bangladesh Institute of Nuclear Agriculture (BINA), Bangladesh. Locally available popular cultivar BARI Soybean-5 was used as a parent material and subjected to five different doses of Gamma ray using Co60. In respect to seed yield and yield attributing characters, twelve true breed mutants were selected from M4 generation. High values of heritability and genetic advance with high genotypic coefficient of variance (GCV) for plant height, branch number and pod number were considered as favorable attributes for soybean improvement that ensure expected yield. The mutant SBM-18 obtained from 250Gy provided stable yield performance at diversified environments. It provided maximum seed yield of 3056 kg ha-1 with highest number of pods plant-1 (56). The National Seed Board of Bangladesh (NSB) eventually approved SBM-18 and registered it as a new soybean variety named 'Binasoybean-5' for large-scale planting because of its superior stability in various agro-ecological zones and consistent yield performance.

Resumo No programa de melhoramento da soja, a pressão pela seleção contínua para a resposta das características de rendimento criou um gargalo genético para melhorias da soja por meio da técnica de melhoramento por hibridação. Portanto, foi desenvolvida uma variedade de soja de alto rendimento, aplicando técnicas de reprodução por mutação, na Divisão de Melhoramento de Plantas, no Instituto de Agricultura Nuclear de Bangladesh (BINA), em Bangladesh. A cultivar popular BARI Soybean-5, disponível localmente, foi usada como material original e submetida a cinco doses diferentes de raios gama usando Co60. Em relação ao rendimento de sementes e às características de atribuição de rendimento, 12 mutantes genuínos foram selecionados a partir da geração M4. Altos valores de herdabilidade e avanço genético com alto coeficiente de variância genotípico (GCV) para altura da planta, número de ramos e número de vagens foram considerados atributos favoráveis ​​ao melhoramento da soja, garantindo, assim, a produtividade esperada. O mutante SBM-18, obtido a partir de 250Gy, proporcionou desempenho de rendimento estável em ambientes diversificados e produtividade máxima de sementes de 3.056 kg ha-1 com o maior número de vagens planta-1 (56). O Conselho Nacional de Sementes de Bangladesh (NSB) finalmente aprovou o SBM-18 e o registrou como uma nova variedade de soja, chamada 'Binasoybean-5', para plantio em larga escala por causa de sua estabilidade superior em várias zonas agroecológicas e desempenho de rendimento consistente.

Characterization of the Bipolaris maydis: symptoms and pathogenicity in popcorn genotypes (Zea mays L. ) / Caracterização de Bipolaris maydis: sintomas e patogenicidade em genótipos de milho-pipoca (Zea mays L. )

Southern corn leaf blight (SCLB) is one of the most important corn leaf diseases. Appropriate management strategies and the use of resistant cultivars allow disease control. Therefore, knowing the aspects related to the pathogen and the response of hosts makes it possible to design efficient strategies for selecting genotypes resistant to this disease. In this sense, the objective was to carry out the Bipolaris maydis isolate characterization, evaluating the pathogenicity in different popcorn lines and the symptoms generated in the host after inoculation. The isolate characterization consisted of the macromorphological evaluation of the colonies and the micromorphological evaluation of the conidia in the PDA medium. An experiment was carried out in a greenhouse to evaluate the pathogenicity of the isolate, using 20 inbred lines of popcorn in a randomized block design with four replicates. Inoculation was carried out by spraying leaves, with a suspension containing 1.0 x 104 conidia.ml-1 of the CF/UENF 501 isolate of B. maydis. An incidence assessment and three assessments of disease symptom severity were performed, with seven days intervals between evaluations. The morphological characterization data of the isolate were analyzed using descriptive statistics, and for disease severity, the linear regression model was applied the first-degree model. The variance analysis was performed for the linear and angular coefficients obtained for each treatment. When a difference was found, the Scott-Knott clustering algorithm at 5% significance was applied. The isolate had gray-green colonies, a cottony appearance, and an irregular shape. The lines L353, L354, and L624 show more resistance at the beginning and throughout the evaluations. The high virulence of the CF/UENF 501 isolate made it possible to differentiate the lines in terms of disease intensity and the pattern of symptoms presented.

Mancha-de-Bipolaris é uma das mais importantes doenças foliares do milho. Estratégias de manejo adequadas e o uso de cultivar resistente permitem o controle da doença, mas para tanto, conhecer os aspectos associados ao patógeno e a resposta do hospedeiro é necessário para traçar estratégias eficientes para seleção de genótipos resistentes a essa doença. Neste sentido, objetivou-se realizar a caracterização do isolado de Bipolaris maydis avaliando a patogenicidade em diferentes linhagens de milho-pipoca e os sintomas gerados no hospedeiro a partir da inoculação. A caracterização do isolado consistiu na avaliação macromorfológica das colônias e micromofológica dos conídios em meio nutritivo BDA. Para avaliação da patogenicidade do isolado foi conduzido um experimento em casa de vegetação utilizando 20 linhagens endogâmicas de milho-pipoca, com delineamento em blocos casualizados, com quatro repetições. A inoculação foi realizada por meio de pulverização em folhas, com uma suspensão contendo 1,0 x 104 conídios.ml-1 do isolado CF/UENF 501 de B. maydis. Foi realizada uma avaliação de incidência e três avaliações de severidade dos sintomas da doença, com o intervalo de sete dias para cada avaliação. Os dados da caracterização morfológica do isolado foram analisados por meio da estatística descritiva e para severidade da doença foi aplicado o modelo de regressão linear de primeiro grau. Realizou-se a análise de variância para o coeficiente linear e angular obtido para cada tratamento e quando constatada diferença aplicou-se o agrupamento de médias de Scott-knott a 5% de significância. O isolado apresentou colônias com coloração cinza esverdeado, aspecto algodonoso e forma irregular. As linhagens L353 e L354 e L624 estão entre as linhagens que apresentaram maior resistência no inicio e ao longo das avaliações. A elevada virulência do isolado CF/UENF 501 possibilitou diferenciar as linhagens quanto a intensidade da doença, bem como o padrão dos sintomas apresentados.

Spectrum of ctxB genotypes, antibiogram profiles and virulence genes of Vibrio cholerae serogroups isolated from environmental water sources from Odisha, India.

BACKGROUND: The present study reports on the comprehensive analysis of Vibrio cholerae O1 and non-O1/non-O139 serogroups isolated from environmental water sources during cholera outbreaks, epidemics and surveillance studies between years 2007 to 2019 from different districts of Odisha, India. METHODS: A total of 85 stocked cultures of V. cholerae O1 and non-O1/non-O139 strains were analyzed for different ctxB genotypes, toxic genes, antibiogram profiles through PCR assays and pulsotyped by pulsed-field gel electrophoresis (PFGE). RESULTS: From all V. cholerae strains tested, 51 isolates were O1 Ogawa and the rest 34 strains were non-O1/non-O139. All the V. cholerae O1 strains were altered El Tor variants carrying ctxB1, ctxB3 and ctxB7 genotypes. However, only ctxB1 genotypes were present in V. cholerae non-O1/non-O139. Though non-O1/non-O139 strains were negative by O1 antisera, 20% strains were positive for rfbO1 gene by PCR assay. All the V. cholerae isolates possessed a variety of virulence genes including ace, ctxAB, toxR, zot, hlyA which were in higher percentage in the case of V. cholerae O1. The Vibrio cholerae O1 and non-O1-/non-O139 strains showed multiple antibiotic resistances in 2007 and 2012. The PCR detection of four resistance associated genes (strB, dfrA1, sulll, SXT) confirmed higher prevalence in V. cholerae non-O1/non-O139 strains. The PFGE analysis revealed 3 pulsotypes having 93% similarity among V. cholerae O1 strains. CONCLUSION: This study indicates the changing epidemiology, antibiogram patterns and continuous genetic variation in environmental V. cholerae strains of Odisha over the years. So continuous surveillance is necessary to understand the changing patterns of V. cholerae different serogroups isolated from stool and water samples from Odisha.

Genetic association analysis of 77,539 genomes reveals rare disease etiologies.

The genetic etiologies of more than half of rare diseases remain unknown. Standardized genome sequencing and phenotyping of large patient cohorts provide an opportunity for discovering the unknown etiologies, but this depends on efficient and powerful analytical methods. We built a compact database, the 'Rareservoir', containing the rare variant genotypes and phenotypes of 77,539 participants sequenced by the 100,000 Genomes Project. We then used the Bayesian genetic association method BeviMed to infer associations between genes and each of 269 rare disease classes assigned by clinicians to the participants. We identified 241 known and 19 previously unidentified associations. We validated associations with ERG, PMEPA1 and GPR156 by searching for pedigrees in other cohorts and using bioinformatic and experimental approaches. We provide evidence that (1) loss-of-function variants in the Erythroblast Transformation Specific (ETS)-family transcription factor encoding gene ERG lead to primary lymphoedema, (2) truncating variants in the last exon of transforming growth factor-ß regulator PMEPA1 result in Loeys-Dietz syndrome and (3) loss-of-function variants in GPR156 give rise to recessive congenital hearing impairment. The Rareservoir provides a lightweight, flexible and portable system for synthesizing the genetic and phenotypic data required to study rare disease cohorts with tens of thousands of participants.

BrainGENIE: The Brain Gene Expression and Network Imputation Engine.

In vivo experimental analysis of human brain tissue poses substantial challenges and ethical concerns. To address this problem, we developed a computational method called the Brain Gene Expression and Network-Imputation Engine (BrainGENIE) that leverages peripheral-blood transcriptomes to predict brain tissue-specific gene-expression levels. Paired blood-brain transcriptomic data collected by the Genotype-Tissue Expression (GTEx) Project was used to train BrainGENIE models to predict gene-expression levels in ten distinct brain regions using whole-blood gene-expression profiles. The performance of BrainGENIE was compared to PrediXcan, a popular method for imputing gene expression levels from genotypes. BrainGENIE significantly predicted brain tissue-specific expression levels for 2947-11,816 genes (false-discovery rate-adjusted p < 0.05), including many transcripts that cannot be predicted significantly by a transcriptome-imputation method such as PrediXcan. BrainGENIE recapitulated measured diagnosis-related gene-expression changes in the brain for autism, bipolar disorder, and schizophrenia better than direct correlations from blood and predictions from PrediXcan. We developed a convenient software toolset for deploying BrainGENIE, and provide recommendations for how best to implement models. BrainGENIE complements and, in some ways, outperforms existing transcriptome-imputation tools, providing biologically meaningful predictions and opening new research avenues.

AMMI-Bayesian perspective in the selection of pre-cultivars of carioca beans in Agreste-Sertão of Pernambuco, Brazil.

The productivity of beans is greatly influenced by the different edaphoclimatic conditions in the Agreste-Sertão region, requiring the identification of adapted and stable genotypes to minimize the effects of the interaction between genotypes per environments (GxE). The objective of this work was to analyze the adaptability and stability of carioca bean pre-cultivars in three municipalities in the Agreste-Sertão of Pernambuco using the AMMI model in its Bayesian version BAMMI and compare the results with the frequentist approach. According to the results, the BAMMI analysis showed better predictive capacity, as well as better performance in the study of adaptability and stability. The cultivar BRS Notável stood out in terms of main effect and stability. Adaptability of genotypes to specific locations was also observed, enabling the use of the positive effect of the GxE interaction, which was more evident with the BAMMI model. From this work, the flexibility of BAMMI model to deal with data resulting from multi-environmental experiments can be seen, overcoming limitations of the standard analysis of the AMMI model.

Fully efficient, two-stage analysis of multi-environment trials with directional dominance and multi-trait genomic selection.

KEY MESSAGE: R/StageWise enables fully efficient, two-stage analysis of multi-environment, multi-trait datasets for genomic selection, including support for dominance heterosis and polyploidy. Plant breeders interested in genomic selection often face challenges to fully utilizing multi-trait, multi-environment datasets. R package StageWise was developed to go beyond the capabilities of most specialized software for genomic prediction, without requiring the programming skills needed for more general-purpose software for mixed models. As the name suggests, one of the core features is a fully efficient, two-stage analysis for multiple environments, in which the full variance-covariance matrix of the Stage 1 genotype means is used in Stage 2. Another feature is directional dominance, including for polyploids, to account for inbreeding depression in outbred crops. StageWise enables selection with multi-trait indices, including restricted indices with one or more traits constrained to have zero response. For a potato dataset with 943 genotypes evaluated over 6 years, including the Stage 1 errors in Stage 2 reduced the Akaike Information Criterion (AIC) by 29, 67, and 104 for maturity, yield, and fry color, respectively. The proportion of variation explained by heterosis was largest for yield but still only 0.03, likely because of limited variation for the genomic inbreeding coefficient. Due to the large additive genetic correlation (0.57) between yield and maturity, naïve selection on an index combining yield and fry color led to an undesirable response for later maturity. The restricted index coefficients to maximize genetic merit without delaying maturity were identified. The software and three vignettes are available at https://github.com/jendelman/StageWise .

Validation with single-step SNPBLUP shows that evaluations can continue using a single mean of genotyped individuals, even with multiple breeds.

BACKGROUND: In genomic prediction, it is common to centre the genotypes of single nucleotide polymorphisms based on the allele frequencies in the current population, rather than those in the base generation. The mean breeding value of non-genotyped animals is conditional on the mean performance of genotyped relatives, but can be corrected by fitting the mean performance of genotyped individuals as a fixed regression. The associated covariate vector has been referred to as a 'J-factor', which if fitted as a fixed effect can improve the accuracy and dispersion bias of sire genomic estimated breeding values (GEBV). To date, this has only been performed on populations with a single breed. Here, we investigated whether there was any benefit in fitting a separate J-factor for each breed in a three-way crossbred population, and in using pedigree-based expected or genome-based estimated breed fractions to define the J-factors. RESULTS: For body weight at 7 days, dispersion bias decreased when fitting multiple J-factors, but only with a low proportion of genotyped individuals with selective genotyping. On average, the mean regression coefficients of validation records on those of GEBV increased with one J-factor compared to none, and further increased with multiple J-factors. However, for body weight at 35 days this was not observed. The accuracy of GEBV remained unchanged regardless of the J-factor method used. Differences between the J-factor methods were limited with correlations approaching 1 for the estimated covariate vector, the estimated coefficients of the regression on the J-factors, and the GEBV. CONCLUSIONS: Based on our results and in the particular design analysed here, i.e. all the animals with phenotype are of the same type of crossbreds, fitting a single J-factor should be sufficient, to reduce dispersion bias. Fitting multiple J-factors may reduce dispersion bias further but this depends on the trait and genotyping rate. For the crossbred population analysed, fitting multiple J-factors has no adverse consequences and if this is done, it does not matter if the breed fractions used are based on the pedigree-expectation or the genomic estimates. Finally, when GEBV are estimated from crossbred data, any observed bias can potentially be reduced by including a straightforward regression on actual breed proportions.

Genotypic and phenotypic characterization of glucose-6-phosphate dehydrogenase (G6PD) deficiency in Guangzhou, China.

BACKGROUND: G6PD deficiency is a common inherited disorder worldwide and has a higher incidence rate in southern China. Many variants of G6PD result from point mutations in the G6PD gene, leading to decreased enzyme activity. This study aimed to analyse the genotypic and phenotypic characteristics of G6PD deficiency in Guangzhou, China. METHODS: In this study, a total of 20,208 unrelated participants were screened from 2020 to 2022. G6PD deficiency was further analysed by quantitative enzymatic assay and G6PD mutation analysis. The unidentified genotype of the participants was further ascertained by direct DNA sequencing. RESULTS: A total of 12 G6PD mutations were identified. Canton (c.1376G>T) and Kaiping (c.1388G>A) were the most common variants, and different mutations led to varying levels of G6PD enzyme activity. Comparing the enzyme activities of the 6 missense mutations between the sexes, we found significant differences (P < 0.05) in the enzyme activities of both male hemizygotes and female heterozygotes. Two previously unreported mutations (c.1438A>T and c.946G>A) were identified. CONCLUSIONS: This study provided detailed genotypes of G6PD deficiency in Guangzhou, which could be valuable for diagnosing and researching G6PD deficiency in this area.

The role of SIRT1 level and SIRT1 gene polymorphisms in optic neuritis patients with multiple sclerosis.

THE AIM: To investigate the role of Sirtuin 1 (SIRT1) level and SIRT1 (rs3818292, rs3758391, rs7895833) gene polymorphisms in patients with optic neuritis (ON) and multiple sclerosis (MS). METHODS: 79 patients with ON and 225 healthy subjects were included in the study. ON patients were divided into 2 subgroups: patients with MS (n = 30) and patients without MS (n = 43). 6 ON patients did not have sufficient data for MS diagnosis and were excluded from the subgroup analysis. DNA was extracted from peripheral blood leukocytes and genotyped by real-time polymerase chain reaction. Results were analysed using the program "IBM SPSS Statistics 27.0". RESULTS: We discovered that SIRT1 rs3758391 was associated with a twofold increased odds of developing ON under the codominant (p = 0.007), dominant (p = 0.011), and over-dominant (p = 0.008) models. Also, it was associated with a threefold increased odds ofON with MS development under the dominant (p = 0.010), twofold increased odds under the over-dominant (p = 0.032) models and a 1.2-fold increased odds of ON with MS development (p = 0.015) under the additive model. We also discovered that the SIRT1 rs7895833 was significantly associated with a 2.5-fold increased odds of ON development under the codominant (p = 0.001), dominant (p = 0.006), and over-dominant (p < 0.001) models, and a fourfold increased odds of ON with MS development under the codominant (p < 0.001), dominant (p = 0.001), over-dominant (p < 0.001) models and with a twofold increased odds of ON with MS development (p = 0.013) under the additive genetic model. There was no association between SIRT1 levels and ON with/without MS development. CONCLUSIONS: SIRT1 rs3758391 and rs7895833 polymorphisms are associated with ON and ON with MS development.

Genetic polymorphisms of pharmacogenomic VIP variants in the Hui population from Ningxia Province of China.

Pharmacogenomics has been widely used to study the very important pharmacogenetic (VIP) variants among different populations. However, there is little pharmacogenomic information about the Chinese Hui population. Our research aimed to reveal the outstandingly different loci in the Hui population, and provide a theoretical foundation for personalized drug use in the Hui population, so as to facilitate more effective treatment of diseases. This study genotyped 53 VIP variants of 26 genes in 200 independent Hui individuals based on the Pharmacogenetics and Pharmacogenomics Knowledge Base (PharmGKB). Remarkable differences in the genotype and allele frequencies between the Hui and 26 other populations from the 1000 Genomes Project were assessed using the χ2 test. The genotype and allele frequencies of single nucleotide polymorphisms (SNPs) in PTGS2 (rs20417), NAT2 (rs1801280), NAT2 (rs1208), ACE (rs4291), and CYP2D6 (rs1065852) were considerably different in the Hui population compared with those in the other 26 populations. Besides, using the PharmGKB database, we identified several VIP variants that may alter the drug metabolism of ibuprofen, rofecoxib (PTGS2), captopril (ACE), citalopram, and escitalopram (CYP2D6). We also discovered other variants associated with adverse reactions to cisplatin and cyclophosphamide (NAT2). Our study indicated that the loci of PTGS2 (rs20417), NAT2 (rs1801280 and rs1208), ACE (rs4291), and CYP2D6 (rs1065852) in the Hui population were obviously different from those in the other 26 populations, which provides reliable information for predicting drug efficacy. Besides, it supplements the pharmacogenomic knowledge of the Hui population and lays the foundation for the individualized treatment for the Hui population.

Interaction between aluminum exposure and ApoEε4 gene on cognitive function of in-service workers.

The occurrence and development of cognitive impairment, the early stage of AD, may be affected both by factors of environmental (aluminum exposure) and genetic (ApoEε4 gene). But whether there is an interaction between the two factors on cognitive function is still unknown. To explore the interaction between the two factors on cognitive function of in-service workers. A total of 1121 in-service workers in a large aluminum factory were investigated in Shanxi Province. Cognitive function was assessed by the Mini-mental State Examination (MMSE), the clock-drawing test (CDT), the Digit Span Test (DST, including DSFT and DSBT), the fuld object memory evaluation (FOM), and the verbal fluency task (VFT). The plasma-Al (p-Al) concentrations were measured by inductively coupled plasma-mass spectrometry (ICP-MS) as an internal exposure indicator, and the participants were divided into four Al exposure groups according to the quartile of p-Al concentrations, namely Q1, Q2, Q3, and Q4. ApoE genotype was determined by Ligase Detection Reaction (LDR). The multiplicative model was fitted using non-conditional logistic regression and additive model was fitted using crossover analysis to analyze the interaction between p-Al concentrations and the ApoEε4 gene. Finally, a dose-response relationship between p-Al concentrations and cognitive impairment was observed, with the p-Al concentrations increased, cognitive function performance gradually becomes worse (Ptrend＜0.05), and the risk of cognitive impairment gradually increases (Ptrend＜0.05), mainly in executive/visuospatial impairment, auditory memory impairment (particularly the working memory impairment). And ApoEε4 gene may be a risk factor for cognitive impairment, while no association between the ApoEε2 gene and cognitive impairment is observed. Additionally, an additive but no multiplicative interaction between p-Al concentrations and ApoEε4 gene is observed, and when the two factors work together, the risk of cognitive impairment further increased, of which 44.2% can be attributed to the interaction effect.

Genome characterisation of norovirus GII.P17-GII.17 detected during a large gastroenteritis outbreak in Romania in 2021.

Norovirus (NoV) is one of the leading causes of acute gastroenteritis worldwide. Genotype GII.P17-G.II.17 emerged in Asia between 2013 and 2015 and transiently replaced the GII.4 Sydney 2012 variant circulating at that time. We present the genome characterisation of a GII.P17-GII.17 strain causing a large outbreak in Romania in 2021. Our study shows that the 2021 strain belongs to a novel cluster of genotype GII.17, different from the two previously recognised P.17 clusters. Distinctive substitutions in predicted conformational epitopes of VP1 were identified for this new cluster. Also, our phylogenetic analysis showed the existence of another P.17 cluster grouping strains from France and Canada.

Prevalence and molecular analysis of Cryptosporidium spp. collected from surface water.

Cryptosporidium is an obligate intracellular parasite reported from all over the world. This protozoan infects a wide range of animals as well as humans. Cryptosporidium parvum and Cryptosporidium hominis are the most prevalent infecting species with mild and self-limiting infection in healthy people. The protozoan oocyst is resistant to common water purifiers. Based on emerging evidence, Cryptosporidium is one of waterborne parasites considered a major public health problem in developing and developed countries. In this study, 42 samples were collected from 14 rivers in the catchment area of Lake Urmia in northwest of Iran. Moreover, amplification of SSU rRNA gene was performed, and polymerase chain reaction products were sequenced. The results of sequencing and comparing the sequences with those in the GenBank revealed that all the 17 positive samples were C. parvum, a zoonotic species and one of the most frequent human-infecting species. Considering these data, it is highly important to inhibit the spread of this protozoan by treating livestock and preventing human and animal effluents from entering the water.

[Cholesterol 7α-Hydroxylase Gene-204A/C Polymorphism in Normal and Gestational Diabetic Pregnancies].

Objective: To investigate the cholesterol 7α-hydroxylase gene ( CYP7A1)-204A/C single nucleotide polymorphism and its relationship with the blood lipid levels of pregnant women with gestational diabetes mellitus (GDM) and normal pregnant women. Methods: The genotype and allele frequencies of CYP7A1-204A/C gene polymorphism of 1037 normal pregnant women, the normal controls, and 627 pregnant women with GDM were examined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and blood glucose (Glu) were measured by enzymatic assay. Chemiluminescence determination of plasma insulin (Ins) was conducted. Apolipoproteins A1 (apoA1) and B (apoB) were measured by the turbidimetric immunoassay. Results: Allele frequencies of A and C at the CYP7A1-204A/C polymorphic locus were 0.586 and 0.414, respectively, in the GDM group and 0.557 and 0.443, respectively in the control group. The distribution of genotype frequencies in both groups showed conformity with the Hardy-Weinberg principle. There was no significant difference in allele and genotype frequencies between the GDM group and the control group. In the control group, carriers of the genotype AA were associated with significantly higher concentrations of apoA1 and lower levels of Ins and homeostatic model assessment of insulin resistance (HOMA-IR) compared with those with genotype CC (all P<0.05). In the non-obese subgroup of the control subjects, carriers of the genotype CC were associated with significantly higher plasma TG or apoA1 levels compared with those with genotype AA ( P<0.05). In the GDM group, carriers with genotype AA of CYP7A1-204A/C polymorphism had elevated levels of gestational weight gain (GWG) compared with those with genotype CC ( P<0.05). Conclusion: These results suggest that 204A/C polymorphism in the CYP7A1 gene is not associated with GDM, but may be closely associated with gestational weight gain in pregnant women with GDM. Variants in this locus are strongly associated with plasma apoA1, Ins, and HOMA-IR levels in the controls and elevated plasma TG levels in non-obese controls.

[A study of genetic variants in patients with ischemic stroke in human rat gene orthologues]. / Izuchenie geneticheskikh variantov u patsientov s ishemicheskim insul'tom v chelovecheskikh ortologakh krysinykh genov.

OBJECTIVE: To study the associations of nine genetic variants with the risk and dynamics of recovery (outcome) of ischemic stroke (IS) using the developed protocol for the search for genomic markers based on a bioinformatic approach to the study of single nucleotide polymorphisms (SNPs) in human orthologues of rat genes differentially expressed under conditions of induced cerebral ischemia. MATERIAL AND METHODS: We identified and analyzed nine SNPs in 553 Russians (331 IS patients and 222 controls). The National Institutes of Health Stroke Scale (NIHSS) was used to assess stroke severity. Functional recovery after stroke was assessed using the modified Rankin scale (mRS). The principles of selection of polymorphic markers analyzed in the study were determined according to the protocol developed by us earlier. Selected SNP tags were genotyped using real-time polymerase chain reaction (PCR) TaqMan. RESULTS: The relationship of SNP with both the risk of IS and the dynamics of its recovery was investigated. SNP rs66782529 (LGALS3) was associated with negative IS outcomes (p=0.048). SNPs rs62278647 and rs2316710 (PTX3) were significantly associated with IS risk (p=0.000029 and p=0.0025, respectively). The associations for rs62278647 and rs2316710 were found only in females, suggesting a gender-related PTX3 polymorphism. CONCLUSION: This study not only reveals some new genetic links to IS and its consequences, but also shows how the study of gene variations in a rat model of cerebral ischemia can be useful in the search for genetic markers of this disease in humans.

Microbiomes of a disease-resistant genotype of Acropora cervicornis are resistant to acute, but not chronic, nutrient enrichment.

Chronically high levels of inorganic nutrients have been documented in Florida's coral reefs and are linked to increased prevalence and severity of coral bleaching and disease. Naturally disease-resistant genotypes of the staghorn coral Acropora cervicornis are rare, and it is unknown whether prolonged exposure to acute or chronic high nutrient levels will reduce the disease tolerance of these genotypes. Recently, the relative abundance of the bacterial genus Aquarickettsia was identified as a significant indicator of disease susceptibility in A. cervicornis, and the abundance of this bacterial species was previously found to increase under chronic and acute nutrient enrichment. We therefore examined the impact of common constituents of nutrient pollution (phosphate, nitrate, and ammonium) on microbial community structure in a disease-resistant genotype with naturally low abundances of Aquarickettsia. We found that although this putative parasite responded positively to nutrient enrichment in a disease-resistant host, relative abundances remained low (< 0.5%). Further, while microbial diversity was not altered significantly after 3 weeks of nutrient enrichment, 6 weeks of enrichment was sufficient to shift microbiome diversity and composition. Coral growth rates were also reduced by 6 weeks of nitrate treatment compared to untreated conditions. Together these data suggest that the microbiomes of disease-resistant A. cervicornis may be initially resistant to shifts in microbial community structure, but succumb to compositional and diversity alterations after more sustained environmental pressure. As the maintenance of disease-resistant genotypes is critical for coral population management and restoration, a complete understanding of how these genotypes respond to environmental stressors is necessary to predict their longevity.

Characterizing the genotypic spectrum of retinitis pigmentosa in East Asian populations: a systematic review.

BACKGROUND: Ongoing trials for retinitis pigmentosa (RP) are genotype-specific, with most trials conducted on European cohorts. Due to genetic differences across diverse ancestries and populations, these therapies may not be efficacious in East Asians. MATERIALS AND METHODS: A literature search was conducted from 1966 to September 2022 for cohort studies on East Asian populations reporting on non-syndromic RP genotypes and variants. Population-weighted prevalence was used to determine the genotypes and individual variants across the entire cohort. The carrier prevalence of common variants was compared against those in Europe. RESULTS: A total of 12 articles describing 2,932 clinically diagnosed East Asian RP probands were included. We identified 876 variants across 54 genes. The most common genotypes included USH2A, EYS, RPGR, ABCA4, PRPF31, RHO, RP1, RP2, PDE6B and SNRNP200, with USH2A as the most common (17.1%). Overall, 60.5% of probands with clinically relevant variants were found to have one of the genotypes above, with 543/876 (62.0%) of the variants occurring in these genes. The most frequently reported variant was USH2A missense variant c.2802T>G/p.C934W (4.9%). Carrier prevalence of these variants was significantly different (p < 0.0001) than in Europe. CONCLUSIONS: USH2A was the most commonly affected RP gene in this East Asian cohort, although sub-population analysis revealed distinct genotype prevalence patterns. While the genotypes are similar between East Asia and European cohorts, variants are specific to East Asia. The identification of several prevalent variants in USH2A and EYS provides an opportunity for the development of therapeutics that are relevant for East Asia patients.