Genetic Variants Research Articles

Investigation of Tissue-Specific Distribution and Genetic Variation of Alfalfa Mosaic Virus and Chinese Artichoke Mosaic Virus in Chinese Artichoke (Stachys affinis miq.)

The Chinese artichoke (Stachys affinis syn. S. sieboldii) is a widely cultivated crop, and its rhizome is used as a medicinal vegetable. To investigate the causes of viral diseases in Chinese artichokes, the infection rates of four virus species infecting Chinese artichoke were investigated. Since the Chinese artichoke propagates through its tuber, this study aimed to determine whether viral transmission to the progeny is possible through the tuber, by identifying the virus present in the tuber and investigating its accumulation. First, reverse transcription polymerase chain reaction analysis was performed to detect viruses using total RNA extracted from the flowers, leaves, and tubers of Chinese artichoke plants. Alfalfa mosaic virus (AMV) and Chinese artichoke mosaic virus (ChAMV) had high infectivity in Chinese artichoke and most plants were simultaneously infected with AMV and ChAMV. These viruses were present in all tissues, but their detection frequency and accumulation rates varied across different tissues of the Chinese artichoke. Also, we sequenced the coat protein (CP) genes of AMV and ChAMV to investigate genetic variations of virus between the leaf and tuber. It provides information on CP gene sequences and genetic diversity of isolates identified from new hosts of AM and ChAMV. This study offers valuable insights into the distribution and spread of the ChAMV and AMV viruses within Chinese artichoke plants, which have implications for the management and control of viral infections in crops.

Pros and Cons of APOE4 Homozygosity and Effects on Neuroplasticity, Malnutrition, and Infections in Early Life Adversity, Alzheimer's Disease, and Alzheimer's Prevention.

Fortea et al.'s. (2024) recent data analysis elegantly calls attention to familial late-onset Alzheimer's disease (AD) with APOE4 homozygosity. The article by Grant (2024) reviews the factors associated with AD, particularly the APOE genotype and lifestyle, and the broad implications for prevention, both for individuals with the lifestyles associated with living in resource-rich countries and for those enduring environmental adversity in poverty settings, including high exposure to enteric pathogens and precarious access to healthcare. Grant discusses the issue of APOE genotype and its implications for the benefits of lifestyle modifications. This review highlights that bearing APOE4 could constitute an evolutionary benefit in coping with heavy enteric infections and malnutrition early in life in the critical formative first two years of brain development. However, the critical issue may be that this genotype could be a health concern under shifts in lifestyle and unhealthy diets during aging, leading to severe cognitive impairments and increased risk of AD. This commentary supports the discussions of Grant and the benefits of improving lifestyle for decreasing the risks for AD while providing further understanding and modelling of the early life benefits of APOE4 amidst adversity. This attention to the pathophysiology of AD should help further elucidate these critical, newly appreciated pathogenic pathways for developing approaches to the prevention and management in the context of the APOE genetic variations associated with AD.

Role of genetic variations and protein expression of β-Microsemino protein in intrauterine insemination outcome of unexplained infertile men: A case-control study

Background: Intrauterine insemination (IUI) is often the first-line treatment for unexplained infertility. β-Microsemino protein (MSMB) is an abundant protein in seminal plasma that has an inhibitory effect on spontaneous acrosome reaction. Objective: The present study aimed to evaluate MSMB gene variations and protein expression on IUI success rate in unexplained infertile men. Materials and Methods: A case-control study was performed on 100 unexplained infertile Iranian men referred to the Royan Institute, Tehran, Iran for IUI (50 men with IUI positive result [IUI+], and 50 men with IUI negative result [IUI-]). Couples with female infertility factors (such as hormonal disorders, infrequent menstrual period, abnormality in uterus, fallopian tubes, or ovaries) and men with infections of the male accessory glands, hypogonadotropic hypogonadism, clinical varicocele, retractile testis, genital trauma, drug use, or concurrent hormonal treatment Y chromosome microdeletions, and abnormal karyotype were excluded from the study. The polymerase chain reaction sequencing was performed for the promoter and the coding regions of MSMB functional domains. To study the protein expression, the total protein of sperm was extracted, and sandwich enzyme-linked immunosorbent assay was performed. Results: 4 variations were detected (rs12770171, rs10993994, rs2075894, and rs4517463). None of them showed significant differences between the IUI+ and IUI-groups. The mean value of protein expression did not show any differences between the groups. Conclusion: In conclusion, there is no association between genetic variations of promoter and coding regions of MSMB functional domains as well as its expression with IUI success in unexplained infertile men. Key words: MSMB, Beta microseminoprotein, Infertility, Male infertility.

Mechanisms of lysosomal tubulation and sorting driven by LRRK2.

Lysosomes are dynamic cellular structures that adaptively remodel their membrane in response to stimuli, including membrane damage. Lysosomal dysfunction plays a central role in the pathobiology of Parkinson's disease (PD). Gain-of-function mutations in Leucine-rich repeat kinase 2 (LRRK2) cause familial PD and genetic variations in its locus increase the risk of developing the sporadic form of the disease. We previously uncovered a process we term LYTL (LYsosomal Tubulation/sorting driven by LRRK2), wherein membrane-damaged lysosomes generate tubules sorted into mobile vesicles. Subsequently, these vesicles interact with healthy lysosomes. LYTL is orchestrated by LRRK2 kinase activity, via the recruitment and phosphorylation of a subset of RAB GTPases. Here, we summarize the current understanding of LYTL and its regulation, as well as the unknown aspects of this process.

DISSyphilis and the risk of HIV infection: A Mendelian randomization study.

To assess the causal effect of syphilis on HIV infection by Mendelian randomization analysis. The data of syphilis and HIV infection were obtained from genome-wide association studies, Mendelian randomization analyses were conducted using methods such as weighted median, MR Egger, and inverse variance to evaluate the causal relationship between syphilis and HIV infection. Gene expression data of persons living with HIV (PLWH) and single-cell RNA sequencing profiles were obtained from the GEO database. Analysis involved the identification of key molecules and relevant signaling pathways. MR analysis showed a significant causal relationship between syphilis and HIV infection (WM, OR: 1.098, 95%CI: 1.033-1.217, P = 0.003; IVW, OR: 1.095, 95%CI: 1.048-1.145, P < 0.001). We discovered that rs138697742, a genetic variant related to the RPAIN gene, is associated with HIV infection, and influences the expression of RPAIN, possibly contributing to the progression of the disease. Moreover, single-cell data analysis revealed the cellular communication patterns within PLWH, with monocytes appearing to play a crucial role. In summary, our study reveals a direct causal relationship between syphilis and HIV infection. Additionally, the upregulation of RPAIN gene expression resulting from genetic mutations may serve as a key factor in promoting the progression of HIV infection. Targeting the RPAIN/GALECTIN merges as a promising novel therapeutic target for managing HIV infection.

Insight Into Severe Neonatal COVID-19 Gained Through Whole Exome Sequencing of Twin Neonates.

The genetic basis of neonatal COVID-19 infection, which exhibits a range of severity, has not been investigated. We identified both shared and unique genetic variants involved in antiviral immune responses through whole exome sequencing of an infant who developed severe COVID-19 pneumonia and multisystem inflammatory syndrome and the twin brother also positive for severe acute respiratory syndrome-coronavirus-2, but with only moderate respiratory symptoms.

Identification and analysis of short indels inducing exon extension/shrinkage events.

The search for genetic variants that act as causative factors in human diseases by disrupting the normal splicing process has primarily focused on single nucleotide variants (SNVs). It is worth noting that insertions or deletions (indels) have also been sporadically reported as causative disease variants through their potential impact on the splicing process. In this study, to perform identification of indels inducing exon extension/shrinkage events, we used individual-specific genomes and RNA sequencing (RNA-seq) data pertaining to the corresponding individuals and identified 12 exon extension/shrinkage events that were potentially induced by indels that disrupted authentic splice sites or created novel splice sites in 235 normal individuals. By evaluating the impact of these abnormal splicing events on the resulting transcripts, we found that five events led to the generation of premature termination codons (PTCs), including those occurring within genes associated with genetic disorders. Our analysis revealed that the potential functions of indels have been underexamined, and it is worth considering the possibility that indels may affect splice site usage, using RNA-seq data to discover novel potentially disease-associated mutations.

Accuracy of renovo predictions on variants reclassified over time

BackgroundInterpreting the clinical consequences of genetic variants is the central problem in modern clinical genomics, for both hereditary diseases and oncology. However, clinical validation lags behind the pace of discovery, leading to distressing uncertainty for patients, physicians and researchers. This “interpretation gap” changes over time as evidence accumulates, and variants initially deemed of uncertain (VUS) significance may be subsequently reclassified in pathogenic/benign. We previously developed RENOVO, a random forest-based tool able to predict variant pathogenicity based on publicly available information from GnomAD and dbNFSP, and tested on variants that have changed their classification status over time. Here, we comprehensively evaluated the accuracy of RENOVO predictions on variants that have been reclassified over the last four years.Methodswe retrieved 16 retrospective instances of the ClinVar database, every 3 months since March 2020 to March 2024, and analyzed time trends of variant classifications. We identified variants that changed their status over time and compared RENOVO predictions generated in 2020 with the actual reclassifications.ResultsVUS have become the most represented class in ClinVar (44.97% vs. 9.75% (likely) pathogenic and 40,33% (likely) benign). The rate of VUS reclassification is linear and slow compared to the rate of VUS reporting, exponential and currently ~ 30x faster, creating a growing divide between what can be sequenced vs. what can be interpreted. Out of 10,196 VUS variants in January 2020 that have undergone a clinically meaningful reclassification to march 2024, RENOVO correctly classified 82.6% in 2020. In addition, RENOVO correctly identified the majority of the few variants that switched clinically meaningful classes (e.g., from benign to pathogenic and vice versa). We highlight variant classes and clinically relevant genes for which RENOVO provides particularly accurate estimates. In particularly, genes characterized by large prevalence of high- or low-impact variants (e.g., POLE, NOTCH1, FANCM etc.). Suboptimal RENOVO predictions mostly concern genes validated through dedicated consortia (e.g., BRCA1/2), in which RENOVO would anyway have a limited impact.ConclusionsTime trend analysis demonstrates that the current model of variant interpretation cannot keep up with variant discovery. Machine learning-based tools like RENOVO confirm high accuracy that can aid in clinical practice and research.

Biallelic HMGXB4 loss-of-function variant causes intellectual disability, developmental delay, and dysmorphic features

BackgroundHMGXB4 (additionally known as HMG2L1) is a non-histone DNA-binding protein that contains a single HMG-box domain. HMGXB4 was originally described in Xenopus where it was seen to negatively regulate the Wnt/β-catenin signaling pathway. Materials and methodsIn this study, we conducted a genetic and clinical evaluation of a single family with three affected individuals suffering from intellectual disability (ID), global developmental delay (GDD) and dysmorphic facial features.Whole genome sequencing (WGS) and Sanger sequencing were performed on the affected individuals' DNA to identify genetic variations. Additionally, a reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to assess gene expression in both the affected and unaffected individuals in the family. ResultWGS identified a homozygous frameshift variant c.1193_1196del p. (Lys398Argfs × 25) in exon 5 of the HMGXB4 gene (OMIM 604702), which completely segregated the disease phenotype in the family. Furthermore, RT-qPCR revealed a substantial decrease in the HMGXB4 gene expression in the affected individuals as compared to the unaffected individuals of the family. ConclusionsThe current study is the first evidence linking a genetic variant in the HMGXB4 gene to ID, GDD, and dysmorphic facial features. Therefore, it is possible that HMGXB4 contributes significantly to developmental milestones and may be responsible for neurodevelopmental disorders in humans.

Identification of genetic susceptibility for Chinese migraine with depression using machine learning

BackgroundMigraine is a common primary headache that has a significant impact on patients’ quality of life. The co-occurrence of migraine and depression is frequent, resulting in more complex symptoms and a poorer prognosis. The evidence suggests that depression and migraine comorbidity share a polygenic genetic background.ObjectiveThe aim of this study is to identify related genetic variants that contribute to genetic susceptibility to migraine with and without depression in a Chinese cohort.MethodsIn this case-control study, 263 individuals with migraines and 223 race-matched controls were included. Eight genetic polymorphism loci selected from the GWAS were genotyped using Sequenom’s MALDI-TOF iPLEX platform.ResultsIn univariate analysis, ANKDD1B rs904743 showed significant differences in genotype and allele distribution between migraineurs and controls. Furthermore, a machine learning approach was used to perform multivariate analysis. The results of the Random Forest algorithm indicated that ANKDD1B rs904743 was a significant risk factor for migraine susceptibility in China. Additionally, subgroup analysis by the Boruta algorithm showed a significant association between this SNP and migraine comorbid depression. Migraineurs with depression have been observed to have worse scores on the Beck Anxiety Inventory (BAI) and the Migraine Disability Assessment Scale (MIDAS).ConclusionThe study indicates that there is an association between ANKDD1B rs904743 and susceptibility to migraine with and without depression in Chinese patients.

Uncovering hidden genetic variations: long-read sequencing reveals new insights into tuberous sclerosis complex

BackgroundTuberous sclerosis is a multi-system disorder caused by mutations in either TSC1 or TSC2. The majority of affected patients (85%–90%) have heterozygous variants, and a smaller number (around 5%) have mosaic variants. Despite using various techniques, some patients still have “no mutation identified” (NMI).MethodsWe hypothesized that the causal variants of patients with NMI may be structural variants or deep intronic variants. To investigate this, we sequenced the DNA of 26 tuberous sclerosis patients with NMI using targeted long-read sequencing.ResultsWe identified likely pathogenic/pathogenic variants in 13 of the cases, of which 6 were large deletions, four were InDels, two were deep intronic variants, one had retrotransposon insertion in either TSC1 or TSC2, and one was complex rearrangement. Furthermore, there was a de novo Alu element insertion with a high suspicion of pathogenicity that was classified as a variant of unknown significance.ConclusionOur findings expand the current knowledge of known pathogenic variants related to tuberous sclerosis, particularly uncovering mosaic complex structural variations and retrotransposon insertions that have not been previously reported in tuberous sclerosis. Our findings suggest a higher prevalence of mosaicism among tuberous sclerosis patients than previously recognized. Our results indicate that long-read sequencing is a valuable approach for tuberous sclerosis cases with no mutation identified (NMI).

Genetic Variants in Vitamin-D Metabolism Genes (rs1155563, rs12785878 and rs10500804) among Females with Type-2 Diabetes Mellitus in Saudi Arabia

Background &amp; Objective: Hypovitaminosis D has shown to be linked with T2DM development and control in numerous studies. The association of SNPs in genes related to VitD metabolism with T2DM has not been sufficiently studied. Consequently, our aim in the present study was to explore the association between genetic variants in genes connected with VitD, mainly a SNP in GC (rs1155563), a SNP in DHCR7 (rs12785878) and a SNP in CYP2R1 (rs10500804) with glycaemic parameters in females with T2DM in Saudi Arabia. Methods: The cross-sectional study included 149 females (age 38-52 years) with T2DM from Jeddah, Saudi Arabia (September 2022-March 2023). Blood was extracted from the participants for biochemical tests including measuring VitD [25(OH)D] concentration, parameters of glycaemia (HbA1c, insulin, fasting glucose and insulin sensitivity indices including HOMA2-IR and HOMA2-%β), and for genomic DNA isolation. Sanger DNA sequencing was used to screen for VitD genetic polymorphisms (rs1155563, rs12785878 and rs10500804). Results: Minor allele frequency for rs1155563C, rs12785878T and rs10500804G was 0.21, 0.23 and 0.37, respectively. Levels of 25(OH)D and glycaemic parameters as well did not show any significant difference between the genotypes of each SNP. Conclusion: This study showed lack of association of rs1155563 in GC, rs12785878 in DHCR7 and rs10500804 in CYP2R1 with VitD level primarily and with glycaemic parameters secondarily. Additional research is required to explore further other VitD genetic polymorphisms influencing T2DM which might lead consequently to genetically-based personalized management for T2DM. doi: https://doi.org/10.12669/pjms.40.8.9318 How to cite this: Alharazy S. Genetic Variants in Vitamin-D Metabolism Genes (rs1155563, rs12785878 and rs10500804) among Females with Type-2 Diabetes Mellitus in Saudi Arabia. Pak J Med Sci. 2024;40(8):---------. doi: https://doi.org/10.12669/pjms.40.8.9318 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Use of genetic correlations to examine selection bias.

Observational studies are rarely representative of their target population because there are known and unknown factors that affect an individual's choice to participate (the selection mechanism). Selection can cause bias in a given analysis if the outcome is related to selection (conditional on the other variables in the model). Detecting and adjusting for selection bias in practice typically requires access to data on nonselected individuals. Here, we propose methods to detect selection bias in genetic studies by comparing correlations among genetic variants in the selected sample to those expected under no selection. We examine the use of four hypothesis tests to identify induced associations between genetic variants in the selected sample. We evaluate these approaches in Monte Carlo simulations. Finally, we use these approaches in an applied example using data from the UK Biobank (UKBB). The proposed tests suggested an association between alcohol consumption and selection into UKBB. Hence, UKBB analyses with alcohol consumption as the exposure or outcome may be biased by this selection.

Genetic variations and gene expression profiles of Rice Black-streaked dwarf virus (RBSDV) in different host plants and insect vectors: insights from RNA-Seq analysis

Rice black-streaked dwarf virus (RBSDV) is an etiological agent of a destructive disease infecting some economically important crops from the Gramineae family in Asia. While RBSDV causes high yield losses, genetic characteristics of replicative viral populations have not been investigated within different host plants and insect vectors. Herein, eleven publicly available RNA-Seq datasets from Chinese RBSDV-infected rice, maize, and viruliferous planthopper (Laodelphax striatellus) were obtained from the NCBI database. The patterns of SNP and RNA expression profiles of expected RBSDV populations were analyzed by CLC Workbench 20 and Geneious Prime software. These analyses discovered 2,646 mutations with codon changes in RBSDV whole transcriptome and forty-seven co-mutated hotspots with high variant frequency within the crucial regions of S5-1, S5-2, S6, S7-1, S7-2, S9, and S10 open reading frames (ORFs) which are responsible for some virulence and host range functions. Moreover, three joint mutations are located on the three-dimensional protein of P9-1. The infected RBSDV-susceptible rice cultivar KTWYJ3 and indigenous planthopper datasets showed more co-mutated hotspot numbers than others. Our analyses showed the expression patterns of viral genomic fragments varied depending on the host type. Unlike planthopper, S5-1, S2, S6, and S9-1 ORFs, respectively had the greatest read numbers in host plants; and S5-2, S9-2, and S7-2 were expressed in the lowest level. These findings underscore virus/host complexes are effective in the genetic variations and gene expression profiles of plant viruses. Our analysis revealed no evidence of recombination events. Interestingly, the negative selection was observed at 12 RBSDV ORFs, except for position 1015 in the P1 protein, where a positive selection was detected. The research highlights the potential of SRA datasets for analysis of the virus cycle and enhances our understanding of RBSDV’s genetic diversity and host specificity.

Genome-wide association study for polledness, horn shape, and wool traits in Original Valachian sheep

Abstract. The Original Valachian sheep is an endangered Slovak national breed that is well adapted to high-altitude pastures. The sheep can be horned with various shapes and can have multi-coloured or completely white or black wool. Breeders are interested in learning about the genetic basis of these traits. We conducted a genome-wide association study based on the genomic information of 96 sheep genotyped by the GeneSeek GGP Ovine 50K SNP (single-nucleotide polymorphism) chip and on the following traits: polledness (presence or absence of horns), horn shape, and wool colour (completely white and completely black). The univariate linear mixed model was used to discover genetic variants significantly associated with tested traits. The Bonferroni correction and the false-discovery rate were used as significance thresholds. The RXFP2 gene (chromosome 10, 29.5 Mb) was identified as a strong candidate for polledness. In addition, when compared to animals with sideways-turned horns vs. polled, the region around the ADAMTS3 gene (chromosome 6, 88.47 Mb) was significant. A total of nine significant genomic regions were found when comparing the sideways-turned spiral horns with the backwards-curled horns, the two most frequent horn types in Original Valachian sheep. The RXFP2 may also contribute to the genetic control of horn shape. Genes identified in other regions were involved to osteogenic differentiation and osteoblast proliferation (PCP4, chromosome 1, 260.7 Mb), bone mineral density and mineral content (NKX1-2, chromosome 22, 43.75 Mb). The significant genetic variants close to the region of MC1R (chromosome 14, at 14.2 Mb) were associated with the wool colour of sheep that were fully white or fully black animals. The results of this study will contribute to a better understanding of the phenotypic variability of the Original Valachian sheep, especially regarding traits that are very important for breeders of this endangered breed.

Designing a single-arm phase 2 clinical trial of mitapivat for adult patients with erythrocyte membranopathies (SATISFY): a framework for interventional trials in rare anaemias – pilot study protocol

IntroductionMembranopathies encompass haemolytic disorders arising from genetic variants in erythrocyte membrane proteins, including hereditary spherocytosis and stomatocytosis. Congenital dyserythropoietic anaemia type II (CDA II) is associated with the SEC23B gene...

Pharmacogenetic determinants of tenofovir diphosphate and lamivudine triphosphate concentrations in people with HIV/HBV coinfection.

The nucleos(t)ide analogs require phosphorylation to the pharmacologically active anabolites in cells. We investigated the hypothesis that single-nucleotide polymorphisms (SNPs) in genes that encode transporters and phosphodiesterase (PDE) enzymes involved in tenofovir (TFV), disoproxil fumarate (TDF), and lamivudine (3TC) disposition will be associated with concentrations of their phosphate anabolites and virologic response. Individuals with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) coinfection receiving TDF/3TC-containing antiretroviral therapy were enrolled. Steady-state TFV diphosphate (TFV-DP) and 3TC triphosphate (3TC-TP) concentrations in peripheral blood mononuclear cells (PBMCs) and dried blood spot samples were quantified. The relationship between genetic variants and TFV-DP and 3TC-TP concentrations as well as with virologic response were examined using multivariable linear regression. Of the 136 participants (median age 43 years; 63% females), 6.6% had HBV non-suppression, and 7.4% had HIV non-suppression. The multidrug resistance protein 2 (encoded by ABCC2 rs2273697) SNP was associated with 3TC-TP concentrations in PBMCs. The human organic anion transporter-1 (encoded by SLC28A2) rs11854484 SNP was associated with HIV non-suppression, and when evaluated together with SNPs with marginal associations (ABCC2 rs717620 and PDE1C rs30561), participants with two or three variants compared to those with none of these variants had an adjusted odds ratio of 48.3 (confidence interval, 4.3-547.8) for HIV non-suppression. None of the SNPs were associated with HBV non-suppression. Our study identified ABCC2 SNP to be associated with 3TC-TP concentrations in PBMCs. Also, a combination of genetic variants of drug transporters and PDE was associated with HIV non-suppression.

Low-Penetrance Susceptibility Variants in Colorectal Cancer—Current Outlook in the Field

Colorectal cancer (CRC) is one of the most frequent and mortality-causing neoplasia, with various distributions between populations. Strong hereditary predispositions are the causatives of a small percentage of CRC, and most cases have no transparent genetic background. This is a vast arena for exploring cancer low-susceptibility genetic variants. Nonetheless, the research that has been conducted to date has failed to deliver consistent conclusions and often features conflicting messages, causing chaos in this field. Therefore, we decided to organize the existing knowledge on this topic. We screened the PubMed and Google Scholar databases. We drew up markers by gene locus gathered by hallmark: oncogenes, tumor suppressor genes, genes involved in DNA damage repair, genes involved in metabolic pathways, genes involved in methylation, genes that modify the colonic microenvironment, and genes involved in the immune response. Low-penetration genetic variants increasing the risk of cancer are often population-specific, hence the urgent need for large-scale testing. Such endeavors can be successful only when financial decision-makers are united with social educators, medical specialists, genetic consultants, and the scientific community. Countries’ policies should prioritize research on this subject regardless of cost because it is the best investment. In this review, we listed potential low-penetrance CRC susceptibility alleles whose role remains to be established.

Associations of ACE I/D and AGTR1 rs5182 polymorphisms with diabetes and their effects on lipids in an elderly Chinese population

BackgroundDiabetes mellitus is generally accompanied by dyslipidaemia, but inconsistent relationships between lipid profiles and diabetes are noted. Moreover, genetic variations in insertion/deletion (I/D) polymorphisms at angiotensin-converting enzyme gene (ACE) and T/C polymorphisms in the angiotensin type 1 receptor gene (AGTR1) are related to diabetes and lipid levels, but the associations are controversial. Thus, the current research aimed to explore the effects of ACE I/D, AGTR1 rs5182 and diabetes mellitus on serum lipid profiles in 385 Chinese participants with an average age of 75.01 years.MethodsThe ACE I/D variant was identified using the polymerase chain reaction (PCR) method, whereas the AGTR1 rs5182 polymorphism was identified using the PCR-based restriction fragment length polymorphism (PCR-RFLP) method and verified with DNA sequencing. Total cholesterol (TC), triglyceride (TG), apolipoprotein A (ApoA), apolipoprotein B (ApoB), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels were measured using routine methods, and the lipid ratios were calculated.ResultsACE I/D, but not AGTR1 rs5182, was a predictor of TG/HDL-C for the whole study population. Both ACE I/D and AGTR1 rs5182 were predictors of HDL-C and LDL-C levels in females but not in males. Moreover, in females, diabetes mellitus and ACE I/D were identified as predictors of TG and TG/HDL-C, whereas AGTR1 rs5182 and diabetes mellitus were predictors of TG/HDL-C. Moreover, diabetes mellitus and the combination of ACE I/D and AGTR1 rs5182 variations were predictors of TG and TG/HDL-C exclusively in females.ConclusionsThe results demonstrated the potential for gender-dependent interactions of ACE I/D, AGTR1 rs5182, and diabetes on lipid profiles. These findings may serve as an additional explanation for the inconsistent changes of blood lipids in individuals with diabetes mellitus, thereby offering a novel perspective for the clinical management of blood lipid levels in diabetic patients.

Iraqi patients with a single-nucleotide polymorphism of interleukin-10 -1082G/A and interleukin-6 -174G/C susceptibility to asthma

The effects of genetic variations in the IL-10 -1082G/A gene and IL-6 -174G/C gene, as well as the genotypes and alleles linked to the prevalence of asthma disease, were investigated using a molecular and immunological study. Between October 2018 and the end of July 2020, 40 healthy individuals (20 females and 20 males) served as a control group for the study, which involved 50 asthmatic patients (31 females and 19 males) at the Allergy Centre, Al-Anbar Teaching Hospital, in Al-Anbar City. The study used the Single Specific Primer-Polymerase Chain Reaction (SSP-PCR) technique to show that the single nucleotide polymorphisms IL-10 -1082G/A and IL-6 -174G/C had a considerably high prevalence rate (P&lt;0.05) among asthma case and that there was an association between the polymorphism and the asthma risk. The findings indicate that asthma patients had considerably higher (P&lt;0.05) IL-10 A alleles and heterozygous GA genotypes (1082G/A) compared to the control group. Genetic variations affecting IL-10 production and the genotypes affecting IL-10 serum levels are associated with the occurrence of asthma and are attributed to the IL-10 -1082G/A promoter gene polymorphism. There was a strong correlation between cytokine levels, of disease development, and the genotypes of the AA and AG genes, indicating that IL-10 -1082A/G predisposition to asthma may be influenced by the gene promoter polymorphism. Asthma development and immunological markers (IL-10) are substantially correlated. One theory links allergic rhinitis to both the development of asthma and its risk. Inducing long-term immunological and clinical tolerance in patients was a good use of HDM immunotherapy. The current study's findings indicate a substantial difference between the asthma patients and the control group in terms of gene type and allele frequency of the IL-6 -174G/C polymorphism. The patients exhibited a higher prevalence of the G allele and the GG homozygous genotype than the control group. Therefore, it was shown that those with GG genotypes had a 2-fold increased probability of having asthma, indicating that patients were more prone to the condition.