Presence Of Single Nucleotide Polymorphisms Research Articles

Klotho genetic variants mediate the association between obstructive sleep apnea and short telomere length

The core features of obstructive sleep apnea (OSA) can potentially contribute to the acceleration of telomere shortening mechanisms. Other factor associated with telomeres is Klotho gene as it can negatively regulates telomerase activity. Noteworthy, KLOTHO protein level has recently been associated with OSA. In this sense, it was plausible to hypothesize that OSA would be associated with short telomere length and those with OSA plus risk single nucleotide polymorphisms (SNPs) in Klotho gene would present even shorter telomere length. As part of the EPISONO cohort, 1042 individuals answered questionnaires, underwent polysomnography and had blood collected for DNA extraction. OSA was defined according to AHI≥ 15 events/hour. Leukocyte telomere length (LTL) was measured through real-time polymerase chain reaction (qPCR) and Klotho SNPs were genotyped by array. Mediation analyses considered the presence of SNPs in Klotho gene and how this interaction can affect OSA and its consequence in telomere length. All the analyses were corrected for multiple comparisons. LTL was significantly shorter in OSA compared to controls in a severity-dependent manner (B = 0.055; CI = 0.007–0.102; p = 0.02). Among the 43 Klotho SNPs analyzed, we observed that 4 SNPs (rs525014, rs7982726, rs685417 and rs9563124) significantly mediated the association between OSA and short LTL. Klotho gene opens a new venue in OSA research since it can contribute in the increase of knowledge of the mechanisms involved in the consequences of short telomeres in individuals with OSA.

Drug resistance markers within an evolving efficacy of anti-malarial drugs in Cameroon: a systematic review and meta-analysis (1998\u20132020)

BackgroundMalaria remains highly endemic in Cameroon. The rapid emergence and spread of drug resistance was responsible for the change from monotherapies to artemisinin-based combinations. This systematic review and meta-analysis aimed to determine the prevalence and distribution of Plasmodium falciparum drug resistance markers within an evolving efficacy of anti-malarial drugs in Cameroon from January 1998 to August 2020.MethodsThe PRISMA-P and PRISMA statements were adopted in the inclusion of studies on single nucleotide polymorphisms (SNPs) of P. falciparum anti-malarial drug resistance genes (Pfcrt, Pfmdr1, Pfdhfr, Pfdhps, Pfatp6, Pfcytb and Pfk13). The heterogeneity of the included studies was evaluated using the Cochran’s Q and I2 statistics. The random effects model was used as standard in the determination of heterogeneity between studies.ResultsOut of the 902 records screened, 48 studies were included in this aggregated meta-analysis of molecular data. A total of 18,706 SNPs of the anti-malarial drug resistance genes were genotyped from 47,382 samples which yielded a pooled prevalence of 35.4% (95% CI 29.1–42.3%). Between 1998 and 2020, there was significant decline (P < 0.0001 for all) in key mutants including Pfcrt 76 T (79.9%-43.0%), Pfmdr1 86Y (82.7%-30.5%), Pfdhfr 51I (72.2%-66.9%), Pfdhfr 59R (76.5%-67.8%), Pfdhfr 108 N (80.8%-67.6%). The only exception was Pfdhps 437G which increased over time (30.4%-46.9%, P < 0.0001) and Pfdhps 540E that remained largely unchanged (0.0%-0.4%, P = 0.201). Exploring mutant haplotypes, the study observed a significant increase in the prevalence of Pfcrt CVIET mixed quintuple haplotype from 57.1% in 1998 to 57.9% in 2020 (P < 0.0001). In addition, within the same study period, there was no significant change in the triple Pfdhfr IRN mutant haplotype (66.2% to 67.3%, P = 0.427). The Pfk13 amino acid polymorphisms associated with artemisinin resistance were not detected.ConclusionsThis review reported an overall decline in the prevalence of P. falciparum gene mutations conferring resistance to 4-aminoquinolines and amino alcohols for a period over two decades. Resistance to artemisinins measured by the presence of SNPs in the Pfk13 gene does not seem to be a problem in Cameroon.Systematic review registration PROSPERO CRD42020162620

Assessment of the Role of Selected SMAD3 and SMAD4 Genes Polymorphisms in the Development of Colorectal Cancer: Preliminary Research.

BackgroundColon cancer is one of the most common types of malignant tumor worldwide. The molecular mechanism of colorectal carcinogenesis is very complex and not yet fully understood. The TGFβ (transforming growth factor β) signaling pathway plays a significant role in the development of many cancers, including colorectal cancer pathogenesis. Changes in TGFβ pathway are associated with increased colorectal cancer risk, because this pathway participates in the control of important cellular processes such as cell growth, proliferation, differentiation, or apoptosis. The family of SMAD (similar to mother against decapentaplegic) proteins is closely correlated to this pathway. SMADs genes expression affects modulation of the transcription of many genes, which leads to the inhibition of cell-growth and apoptosis in colon epithelial cells. The presence of SNPs (single nucleotide polymorphisms) in SMADs genes encoding proteins involved in the control of biological processes important for the cell may play a significant role in the predisposition to the development of colorectal cancer, or in the regulation of the severity of changes related to tumor growth. Extension of data in this field may provide clinically significant conclusions influencing the implementation of personalized treatment based on specific changes characteristic of a patient with colorectal cancer.PurposeThe subject of this research was genotyping polymorphisms of SMAD3 (rs6494629) and SMAD4 (rs10502913, rs12968012, rs1057520801) genes in the group of patients with colorectal cancer and in the control group, and comparing the genotypic frequency distributions with clinical-pathological features within the study group and between the groups.Materials and MethodsSNP genotyping analysis was performed on genomic DNA isolated from 84 frozen tissue sections of colorectal cancer and from 60 peripheral blood samples of patients without cancer. To evaluate the polymorphic variants of SMAD genes, the restricted fragment length of a polymorphism reaction (PCR-RFLP) was used.ResultsThe results obtained in the study showed no significant association between the examined polymorphisms and the risk of developing colorectal cancer.ConclusionMore extensive studies to confirm the results obtained in this study are needed. Further studies on a larger study group divided according to the clinical stage and histological differentiation may allow finding or excluding the significance of the studied SNPs as potential markers of colorectal cancer in relation to the clinico-pathological data.

Identification of Allelic Variation in Drought Responsive Dehydrin Gene Based on Sequence Similarity in Chickpea (Cicer arietinum L.).

Chickpea (Cicer arietinum L.) is an economically important food legume grown in arid and semi-arid regions of the world. Chickpea is cultivated mainly in the rainfed, residual moisture, and restricted irrigation condition. The crop is always prone to drought stress which is resulting in flower drop, unfilled pods, and is a major yield reducer in many parts of the world. The present study elucidates the association between candidate gene and morpho-physiological traits for the screening of drought tolerance in chickpea. Abiotic stress-responsive gene Dehydrin (DHN) was identified in some of the chickpea genotypes based on the sequence similarity approach to play a major role in drought tolerance. Analysis of variance revealed a significant effect of drought on relative water content, membrane stability index, plant height, and yield traits. The genotypes Pusa1103, Pusa362, and ICC4958 were found most promising genotypes for drought tolerance as they maintained the higher value of osmotic regulations and yield characters. The results were further supported by a sequence similarity approach for the dehydrin gene when analyzed for the presence of single nucleotide polymorphisms (SNPs) and indels. Homozygous indels and single nucleotide polymorphisms were found after the sequencing in some of the selected genotypes.

Genomic Association of Single Nucleotide Polymorphisms with Blood Pressure Response to Hydrochlorothiazide among South African Adults with Hypertension.

This study described single nucleotide polymorphisms (SNPs) in hydrochlorothiazide-associated genes and further assessed their correlation with blood pressure control among South African adults living with hypertension. A total of 291 participants belonging to the Nguni tribes of South Africa on treatment for hypertension were recruited. Nineteen SNPs in hydrochlorothiazide pharmacogenes were selected and genotyped using MassArray. Uncontrolled hypertension was defined as blood pressure ≥140/90 mmHg. The association between genotypes, alleles and blood pressure response to treatment was determined by conducting multivariate logistic regression model analysis. The majority of the study participants were female (73.19%), Xhosa (54.98%) and had blood pressure ≥140/90 mmHg (68.73%). Seventeen SNPs were observed among the Xhosa tribe, and two (rs2070744 and rs7297610) were detected among Swati and Zulu participants. Furthermore, alleles T of rs2107614 (AOR = 6.69; 95%CI 1.42–31.55; p = 0.016) and C of rs2776546 (AOR = 3.78; 95%CI 1.04–13.74; p = 0.043) were independently associated with uncontrolled hypertension, whilst rs2070744 TC (AOR = 38.76; 95%CI 5.54–270.76; p = 0.00023), CC (AOR = 10.44; 95%CI 2.16–50.29; p = 0.003) and allele T of rs7297610 (AOR = 1.86; 95%CI 1.09–3.14; p = 0.023) were significantly associated with uncontrolled hypertension among Zulu and Swati participants. We confirmed the presence of SNPs associated with hydrochlorothiazide, some of which were significantly associated with uncontrolled hypertension in the study sample. Findings open doors for further studies on personalized therapy for hypertension in the country.

Genomic insights of international clones of Haemophilus influenzae causing invasive infections in vaccinated and unvaccinated infants

The emergence of invasive Haemophilus influenzae infections in vaccinated patient is a public health concern. We have investigated the genomic basis of invasiveness and possible vaccine failure in H. influenzae causing invasive disease in vaccinated and unvaccinated children in Brazil. Three H. influenzae strains isolated from blood cultures of pediatric patients were sequenced. Serotype, MLST, resistome and virulome were predicted using bioinformatic tools, whereas single nucleotide polymorphisms (SNPs) analysis of cap loci and the presence of the putative virulence-enhancing IS1016-bexA partial deletion were predicted in silico. Infections were caused by H. influenzae type a (Hia), type b (Hib) and nontypeable (NTHi), belonging to international high-risk clones of sequence types ST23, ST6 and ST368, respectively, which have been identified in North American, European and Asian countries. Convergence of ampicillin resistance and virulence in Hib-ST6 was supported by blaTEM-1B and deletion in the bexA gene, whereas presence of SNPs in the cap-b locus was associated with antigenic modifications of the capsule structure. Hia-ST23 and NTHi-ST368 strains carried galU, lpsA, opsX, rfaF, iga1, lgtC and lic1/lic2 virulence genes, associated with colonization, adaptation and damage to the lung, or invasiveness. In summary, deletion in the bexA gene and presence of SNPs in the cap locus of Hib could be contributing to invasive disease and possible vaccine failure in pediatric patients, whereas serotype replacement of Hib with type “a” and NTHi strains denotes the ability of non-vaccine serotypes to re-colonize vaccinated patients. Finally, the dissemination of international high-risk clones of H. influenzae emphasizes the importance of monitoring changes in the molecular epidemiology of invasive H. influenzae disease.

The miR-146a SNP Rs2910164 and miR-155 SNP rs767649 Are Risk Factors for Non-Small Cell Lung Cancer in the Iranian Population.

Background Lung cancer is one of the leading causes of death worldwide. MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression and may act as both tumor suppressors and as oncogenes. The presence of single nucleotide polymorphisms (SNPs) inside the miRNA genomic region could affect target miRNA maturation, expression, and binding to its target mRNA and contribute to cancer development. Previous studies on the SNPs Rs2910164 in miR-146a and Rs767649 in miR-155 showed association with non-small cell lung cancer (NSCLC) development. Thus, the aim of this study was to detect any correlation between those SNPs in Iranian NSCLC patients. Methods In a small cohort study, 165 NSCLC patients and 147 noncancer controls were enrolled between Apr 2015 and Sep 2019 at the Masih Daneshvari Hospital, Tehran, Iran. Allele frequencies from the genomic DNA of blood cells were studied using PCR-RFLP and their association with the risk of lung cancer was evaluated. Results The rs2910164C allele (OR = 1.56, 95% CI = 1.10–2.21, p = 0.012) and CC genotype (OR = 2.93, 95% CI = 1.07–7.9, p = 0.034, respectively) were associated with a significantly increased risk for lung cancer compared to that for the GG genotype. When patients were stratified according to smoking exposure, no association with rs2910164 variants was found. The AT genotype (OR = 0.57, 95% CI = 0.33–0.99, p = 0.048) and the A allele frequency (OR = 0.58, 95% CI = 0.35–0.98, p = 0.043) in rs767649 were lower in NSCLC patients in comparison with the control group. In addition, the rs767649 AT genotype frequency in smoking controls was higher than in smoking NSCLC patients (OR = 0.44, 95% CI = 0.21–0.90, p = 0.024). No association was found between rs2910164 and rs767649 variants and stage or type of NSCLC. Conclusion Our finding suggests that miR-146a rs2910164 and miR-155 rs767649 polymorphisms may be considered as genetic risk factors for the susceptibility to NSCLC in the Iranian population. However, a larger multicenter study across Iran is needed to confirm these findings.

Differential mitochondrial genome in patients with Rheumatoid Arthritis

Background Mitochondria play an important role in cell survival, function and lineage differentiation. Changes in mitochondrial DNA (mtDNA) may control mitochondrial functions and thus may impart an alternative cellular state thereby leading to a disease condition in the body. Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease wherein immune cells become self-reactive causing joint inflammation, swelling and pain in patients. The changes in mtDNA may alter cellular functions thereby directing the immune cells towards an inflammatory phenotype in RA. Therefore, it becomes pertinent to identify changes in mtDNA sequence in immune cells of RA patients to understand the pathogenesis and progression of RA. Methods mtDNA from peripheral blood mono-nuclear cells (PBMCs) of 23 RA patients and 17 healthy controls (HCs) were sequenced using next-generation sequencing (NGS). Further, single nucleotide polymorphisms (SNPs) and other variable changes in mtDNA hypervariable and coding regions, amino acid changes with a putative impact on disease, levels of heteroplasmy, copy number variations and haplogroup analysis in RA patients and HCs were analysed and compared to identify any association of mtDNA changes and RA disease. Results A total of 382 single nucleotide mtDNA variants were observed, 91 (23.82%) were present in hypervariable region and 291 (76.18%) in coding region of patients and HC. The variant 513 GCA > ACA, with G present in HVR-III, known to control the mitochondrial translation function, was significantly present in RA patients. The CYTB gene had larger number of SNPs in HC samples while RNR2 was more variable in RA patients. A non-synonymous heteroplasmy in ND1 gene was found at a single nucleotide position 3533 in an increased number of RA patients as compared to the controls. A significant increase in mtDNA duplication and a higher frequency of the haplogroup U was also characteristic of RA. Also, the presence of SNPs in mitochondrial tRNA genes at two positions 12308 A > G and 15924 A > G were found to be pathogenic. Conclusion We herein observed an altered mtDNA sequence in immune cells of RA patients and thus a possible role of mitochondrial genome in the development of RA. The observed nucleotide changes in mtDNA control region, RNR2 gene, increased heteroplasmy and mtDNA duplication in RA patients may alter sites for transcription factor binding thereby influencing mtDNA gene expression, as well as copy numbers thereby affecting the mitochondrial proteins and their functions. These changes in mtDNA could be one of the probable reasons among many leading to the progression of RA.

Utilization of droplet digital PCR to survey resistance associated polymorphisms in the β tubulin gene of Haemonchus contortus in sheep flocks in Sweden

Infections with gastrointestinal nematodes (GINs) in small ruminants are becoming increasingly harder to treat due to the development of anthelmintic resistance. Across Swedish sheep farms, Haemonchus contortus is one of the more persistent and pathogenic species encountered. Benzimidazole drugs, such as albendazole, are still widely used to control the GIN burden in small ruminants. However, the decline in efficacy of this drug has been observed across the country. In this study, we aimed to continue to investigate the presence of single nucleotide polymorphisms in the β tubulin gene associated with benzimidazole drug resistance in H. contortus. This was carried out for sheep flocks from 67 farms around Sweden by screening for the two most commonly encountered SNPs at codons 167 and 200 in the isotype 1 β tubulin gene utilizing the droplet digital PCR technology. We first established a good agreement (Lin’s concordance correlation coefficient = 0.987) between the previously widely used pyrosequencing assay for the detection of the SNP at codon 200 (otherwise known as mutation F200Y) and our assay, as well as developed and validated primer-probe pairs for the detection of the mutation at codon 167 (mutation F167Y) in the β tubulin gene of H. contortus. We then screened 174 pooled larval culture samples, collected either pre- or post-treatment, for the frequencies of the mutations F167Y and F200Y. Not only did we find the latter to be present at much higher frequencies, but the overall levels of this resistance conferring mutation have stayed stable throughout the years 2014-2019 at an average value of 88.5 ± 20.3% in the pre-treatment samples across the tested farms (p = 0.61, Kruskal-Wallis test). Furthermore, after establishing a mixed model and fitting our data, we found a significant (p < 0.01) difference in the average frequency of the mutation F200Y between paired, pre- and post-treatment with albendazole, samples. Although the frequency difference in samples treated with albendazole was relatively minor (88.5% in pre- and 95.6% in post-treatment), no significant (p = 0.15) change in F200Y mutation frequency was observed between the samples from the flocks treated with ivermectin (90.8% and 92.6 %, respectively).

The Effects of Single Nucleotide Polymorphisms in Cancer RNAi Therapies.

Simple SummaryDespite the recent progress in RNAi delivery of siRNA-based therapeutics for cancer therapy, the presence of single nucleotide polymorphisms (SNPs) in the general population could dramatically reduce the effectiveness of RNAi therapy. Their ubiquitous presence can also lead to unpredictable and adverse side effects. Because both SNPs and somatic mosaicisms have also been implicated in a number of human diseases including cancer, however, these specific changes offer the ability to selectively and efficiently target cancer cells. Here, we discuss how SNPs influence the development and success of novel anticancer RNAi therapies.Tremendous progress in RNAi delivery methods and design has allowed for the effective development of siRNA-based therapeutics that are currently under clinical investigation for various cancer treatments. This approach has the potential to revolutionize cancer therapy by providing the ability to specifically downregulate or upregulate the mRNA of any protein of interest. This exquisite specificity, unfortunately, also has a downside. Genetic variations in the human population are common because of the presence of single nucleotide polymorphisms (SNPs). SNPs lead to synonymous and non-synonymous changes and they occur once in every 300 base pairs in both coding and non-coding regions in the human genome. Much less common are the somatic mosaicism variations associated with genetically distinct populations of cells within an individual that is derived from postzygotic mutations. These heterogeneities in the population can affect the RNAi’s efficacy or more problematically, which can lead to unpredictable and sometimes adverse side effects. From a more positive viewpoint, both SNPs and somatic mosaicisms have also been implicated in human diseases, including cancer, and these specific changes could offer the ability to effectively and, more importantly, selectively target the cancer cells. In this review, we discuss how SNPs in the human population can influence the development and success of novel anticancer RNAi therapies and the importance of why SNPs should be carefully considered.

Single Nucleotide Polymorphisms in Colitis-Associated Colorectal Cancer: A Current Overview with Emphasis on the Role of the Associated Genes Products.

Colitis-Associated Colorectal Cancer (CA-CRC) is one of the most severe complications of Inflammatory Bowel Disease (IBD) and constitutes the cause of death in 10-15% of patients. The risk ratio for carcinogenesis depends on numerous factors, such as the extent of intestinal inflammatory lesions and the duration of the disease. CA-CRC is a major problem of today's gastroenterology and colorectal surgery due to the fact that the incidence and prevalence of IBD are increasing. In this review, we discussed the current state of knowledge regarding genetic differences between sporadic CRC and CA-CRC, especially pertaining to the chromosomal instability mechanism (CIN). In order to explain CA-CRC molecular basis, we have analyzed the data from studies regarding the correlations between CA-CRC and the presence of Single Nucleotide Polymorphisms (SNPs). Further focus on the role of associated proteins has emphasized the role of NF-κB signaling as the main link between inflammation and carcinogenesis during the course of IBD.

Balancing selection at the ATP binding site of heat shock cognate 70 (HSC70) contributes to increased thermotolerance in Artemia franciscana

A number of single-nucleotide polymorphisms (SNPs) in heat shock protein 70 (HSP70) family genes have been reported to be associated with stress tolerance. In this study, the presence of SNPs in either the ArHSP70 and ArHSC70 genes (heat shock cognate gene) was verified in 2 Artemia franciscana populations, either a control population (CF12) or a population selectively bred for increased induced thermotolerance (TF12) over 12 generations. In TF12 animals, a novel non-synonymous SNP was identified at position 171 of the cDNA (C171A; N57K; in the ATP/ADP binding site) in ArHSC70 but not in ArHSP70. Cloning and expression of the 2 allelic forms in yeast (Saccharomyces cerevisiae) confirmed that yeast cells containing an ArHSC70-N57K plasmid could tolerate higher temperatures than yeast cells containing an ArHSC70-wild type plasmid. This strongly suggests that the SNP at C171A (N57K) increases thermotolerance of the TF12 A. franciscana population. Upon analysis of individuals of the CF12 and TF12 populations it appears that the C171A allele frequency increased substantially in the TF12 population. Both populations appear not to be in Hardy-Weinberg equilibrium, with CF12 displaying an apparent lack of heterozygotes, while the TF12 displays a large excess of heterozygotes. It is argued that these observations are a novel case of balancing selection. As such, HSP genes join a group of immune related genes where balancing selection contributes to population fitness.

Genotype of Null Polymorphisms in Genes GSTM1, GSTT1, CYP1A1, and CYP1A1*2A (rs4646903 T>C)/CYP1A1*2C (rs1048943 A>G) in Patients with Larynx Cancer in Southeast Spain.

Simple SummaryEpidemiological studies have shown that individual susceptibility to cancer is mediated by genetic and environmental factors. The aim of the present study is to evaluate the individuals’ metabolic genetic susceptibility to toxic habits (smoking and alcohol consumption) by detecting polymorphisms CYP1A1 rs1048943 T>C and CYPA1A2 rs4646903 A>G, and null polymorphisms in GSTM1 and GSTT1 genotypes, comparing a group of healthy control subjects with a population of larynx cancer patients from southeastern Spain. As results patients with larynx cancer present more gene GSTM1 and GSTT1 null polymorphisms, and CYP1A1 rs4646903 T>C polymorphisms.Background: some types of cancer have been associated with the presence of single nucleotide polymorphisms (SNPs) of some genes that encode enzymes: glutathione-S transferase (GST), whose alteration leads to loss of function and a lower capacity to eliminate toxic GSTM1 and GSTT1 null genotypes; SNPs causing loss of function of CYP1A1 or CYP1A1–2 cytochrome P450 enzymes related with a lower capacity to deactivate hydrocarbons related to smoking, which involves a higher risk of developing some smoking-dependent cancers including larynx cancer. Objective: to compare the presence of null SNPs in genes GSTM1, GSTT1, and CYP1A1 rs 4646903 T>C, and CYP1A1–2 RS1048943 A>G in patients with hypopharyngeal and larynx cancer with a healthy control group. Materials and method: The study included a total of 80 patients with hypopharyngeal and laryngeal cancer and 23 healthy subjects. Genomic DNA was obtained from saliva samples, determining genotype GSTM1 (present +, or null −), GSTT1 (present + or null −). Polymorphisms (SNP) in CYP1A1 T>C (present + CC, or absent − TC/TT), and CYP1A1–2 A>G (present + GG, or absent − AG/AA). Results: the mean age of patients with larynx cancer was 62 years and of control subjects 63 years. Of the total sample, over 95% were men, and over 90% were smokers. The presence of null genotypes for GTM1 was 50% in patients with larynx cancer (p = 0.042), while GSTT1 was 88.75% (p = 0.002). CYP1A1 rs4646903 T>C polymorphisms were detected in 100% of cases of larynx cancer and 17.39% of healthy subjects (p > 0.001). Conclusions: patients with larynx cancer present more gene GSTM1 and GSTT1 null polymorphisms, and CYP1A1 rs4646903 T>C polymorphisms.

Characterization of a SPM-1 metallo-beta-lactamase-producing Pseudomonas aeruginosa by comparative genomics and phenotypic analysis

Pseudomonas aeruginosa is one of the most common pathogens related to healthcare-associated infections. The Brazilian isolate, named CCBH4851, is a multidrug-resistant clone belonging to the sequence type 277. The antimicrobial resistance mechanisms of the CCBH4851 strain are associated with the presence of the bla_text {SPM-1} gene, encoding a metallo-beta-lactamase, in combination with other exogenously acquired genes. Whole-genome sequencing studies focusing on emerging pathogens are essential to identify key features of their physiology that may lead to the identification of new targets for therapy. Using both Illumina and PacBio sequencing data, we obtained a single contig representing the CCBH4851 genome with annotated features that were consistent with data reported for the species. However, comparative analysis with other Pseudomonas aeruginosa strains revealed genomic differences regarding virulence factors and regulatory proteins. In addition, we performed phenotypic assays that revealed CCBH4851 is impaired in bacterial motilities and biofilm formation. On the other hand, CCBH4851 genome contained acquired genomic islands that carry transcriptional factors, virulence and antimicrobial resistance-related genes. Presence of single nucleotide polymorphisms in the core genome, mainly those located in resistance-associated genes, suggests that these mutations may also influence the multidrug-resistant behavior of CCBH4851. Overall, characterization of Pseudomonas aeruginosa CCBH4851 complete genome revealed the presence of features that strongly relates to the virulence and antibiotic resistance profile of this important infectious agent.

Gonadotropine Releasing Hormone (GnRH) Receptor Profile from Cow’s Hypothalamus

Gonadotropine Releasing Hormone (GnRH) is one of the recommended hormones to overcome ovulation problems and it can increase pregnancy rate so that it is used in government programs to increase cattle population in Indonesia, although the results are not yet optimal. The purpose of this study is to compare the composition of bovine GnRH receptor nucleotides with the GenBank reference so that the level of genetic diversity of bovine receptors in Indonesia is known. PCR product sequencing using Promoter F and Exon 1 R primers were further aligned with the reference sequences of Bos Taurus GnRHR mRNA GenBank using the MEGA X program. The results of the analysis found the presence of Single Nucleotide Polymorphism (SNP) in the coding region of 1st cow position 38(A&gt; T), 261(C &gt; T), 342(C &gt;T), 411(C &gt;T) and 495(C &gt; T) and 2nd cow positions 261(C &gt;T). Changes in amino acids were also detected in 1st cow position 13 (H&gt; L). The presence of SNP was found to indicate genomic variation between individuals at cattle receptors in Indonesia.

Association of single nucleotide polymorphisms in TNF-α (−308G/A and −238G/A) to dengue: Case-control and meta-analysis study

Dengue is an acute viral disease whose clinical condition is related to the interaction of factors related to the Dengue virus (DENV), environment and the host, with the immunity of the human host contributing a substantial role in the pathogenesis of DENV infection. Studies have demonstrated that single nucleotide polymorphisms (SNPs) in the promoter regions of cytokine genes such as tumor necrosis factor (TNF-α) affect transcription and/or expression; and therefore, may influence the pathogenesis of infectious diseases, such as dengue. Consequently, the objective of this study was to assess through a case-control study whether there was an association between the presence of SNPs −308G/A and −238G/A in the TNF-α gene and 158 patients with dengue and 123 controls. No association was found between the SNPs and the dengue cases in the study population. We then performed a meta-analysis, retrieving data from case-control studies in the literature for the same polymorphisms. For SNP-308G/A, the GG genotype was associated with dengue fever (DF) risk (OR = 1.24, 1.00–1.53; p = 0.05; I2 = 0%), while the GA genotype (OR = 0.75, 0.60–0.93; p = 0.01; I2 = 0%) and allele A (OR = 0.75, 0.60–0.93; p = 0.01; I2 = 0%) were associated with protection. The genotype GG population in the Asian continent (OR = 1.81 [1.06, 3.09], p = 0.03, I2 = 0%) and American (OR = 1.29 [1.00, 1.65], p = 0.05, I2 = 0%) was also associated with protection in the comparison between the cases versus the control group. In each comparison, the dominant model AA + GA (p < 0.00001) conferred protection. For SNP-238G/A the GA genotype was associated with risk for dengue hemorrhagic fever (DHF; OR = 2.17, 1.28–3.67; p = 0.004; I2 = 0%)), and the dominant AA + GA model (p < 0.00001) was associated with protection in each comparison. In summary, our results did not associate SNPs in the TNF-α gene to dengue in the Brazilian northeast population. However, combined literature data suggested the effect of the GG and GA genotypes of the SNP-308G/A on risk and protection, respectively, in Asian and American populations.

Frequency of MicroRNA Response Elements Identifies Pathologically Relevant Signaling Pathways in Triple-Negative Breast Cancer.

SummaryComplex interactions between mRNAs and microRNAs influence cellular functions. The mRNA-microRNA interactions also determine the post-transcriptional availability of mRNAs and unbound microRNAs. MicroRNAs binds to one or more microRNA response elements (MREs) located on the 3′UTR of mRNAs. In this study, we leveraged MREs and their frequencies in cancer and matched normal tissues to obtain insights into disease-specific interactions between mRNAs and microRNAs. We developed a bioinformatics method “ReMIx” that utilizes RNA sequencing (RNA-Seq) data to quantify MRE frequencies across the transcriptome. We applied ReMIx to triple-negative (TN) breast cancer tumor-normal adjacent pairs and identified MREs specific to TN tumors. ReMIx identified candidate mRNAs and microRNAs in the MAPK signaling cascade. Further analysis of MAPK gene regulatory networks revealed microRNA partners that influence and modulate MAPK signaling. In conclusion, we demonstrate a novel method of using MREs in the identification of functionally relevant mRNA-microRNA interactions in TN breast cancer.

Genetic polymorphisms associated with clostridium difficile infection in multiple myeloma patients undergoing autologous stem cell transplantation.

8522 Background: CDI is the primary cause of infectious diarrhea in immunocompromised patients including those undergoing autologous stem cell transplant (SCT). Given the key role of gut microbiome and its interaction with host immune system, we investigated whether polymorphisms in innate immunity genes (identified through Ingenuity Pathway Analysis) were associated with CDI. Methods: We queried our database to identify MM patients who underwent an autologous SCT between April 2015-June 2019. Patients who had their buccal swabs collected through an IRB approved specimen collection protocol were included herein. Data were collected on age, conditioning regimen, CDI diagnosis, time from admission until CDI diagnosis, absolute neutrophil count (ANC) at time of CDI diagnosis, and antibiotic prophylaxis. Genomic DNA was extracted from buccal swabs and genotyped for 62 single nucleotide polymorphisms (SNPs) in ASPH , RLBP1L1, ATP7B, IL-8, FAK, TNFRSF14, CTH, TLR and IL-4. Univariate and multivariate logistic regression analyses were performed to assess association between CDI and presence of SNPs in these genes. Results: A total of 83 patients were identified (25 cases and 58 controls). Baseline characteristics were comparable between two groups. Median age was 67 years (range: 50-79). All patients received high dose melphalan as conditioning, and the same antibiotic prophylaxis during peri-transplant period. Median time from hospitalization until CDI diagnosis was 10 days (IQR:9 days), and median ANC was 0.7/mL (IQR:1.6/mL). Two SNPs (rs2227307 T &gt; G in IL-8 and rs2234167 G &gt; A in TNFRSF14) were significantly associated with CDI risk in both univariate and multivariate logistic regression analyses (Table). Conclusions: Our findings suggest that rs227307G (in IL-8) and rs2234167A (in TNFRSF14) alleles are potential risk factors for CDI after autologous SCT. Our findings, if validated in a larger cohort, would support genetic testing as a screening tool to identify patients who might benefit from prophylaxis against CDI. [Table: see text]

Salt Taste Genotype, Dietary Habits and Biomarkers of Health: No Associations in an Elderly Cohort.

A small amount of emerging research has observed variations between individual sensitivity, preference and intake of salt in the presence of single nucleotide polymorphisms (SNP) on the genes encoding salt taste receptors. Sodium intake is a significant risk factor for common diseases in elderly populations such as hypertension and cardiovascular disease; however, this does not fully explain the risk. Research into the influence of salt taste genetics on diet quality is yet to be undertaken and current research on indicators of health is limited and mixed in the direction of associations. Therefore, a secondary analysis of data from a well-characterised elderly cohort (the cross-sectional Retirement Health and Lifestyle Study, n = 536) was conducted to explore relationships between the salt taste-related SNP TRPV1-rs8065080 (assessed by Taqman genotyping assay), dietary habits and biomarkers of health. Data were analysed with standard least squares regression modelling and Tukey’s HSD post hoc tests. No association was found between the TRPV1-rs8065080 genotype, sodium intake or multiple diet quality indices (assessed by food frequency questionnaire). Sodium-related markers of health including blood pressure and markers of kidney function (urinary creatinine and albumin/creatinine ratio) and general health markers, such as Body Mass Index (BMI), were also not related to TRPV1-rs8065080 genotype. To date, this study is the most comprehensive investigation conducted to determine if the TRPV1-rs8065080 genotype relates to sodium intake and health markers influenced by sodium intake. Although no significant relationships were found, these findings are an important contribution to the limited body of knowledge surround this SNP. In addition to further research across other ages and cultures, the TRPV1-rs8065080 genotype may interact with other ion channels, and so further studies are required to determine if polymorphic variations influence sodium intake, diet and health.

Genetic Polymorphisms of Glutathione S-Transferase and Risk of Acute Myeloid Leukemia: Case-Control Study and Meta-Analysis

Background: Acute myeloid leukemia (AML) is a complex disease that is linked to genetic and environmental factors. The gluthatione S-transferase (GST) is a family of enzymes that play a crucial role in the detoxification of carcinogens. These compounds could cause DNA damage, which might lead to the development of cancer. Interindividual inherited differences caused by the presence of single nucleotide polymorphisms (SNPs) in detoxification enzyme, could play a major role in cancer predisposition. The present study aimed to investigate the association between GST gene polymorphisms and AML risk. Methods: The GSTP1 genotype was determined by the PCR-RFLP and multiplex PCR for GSTT1 and GSTM1. Meta-analysis was conducted to evaluate the association between GST gene and the risk of AML. Results: We found that GSTT1 null genotype was significantly associated with the risk of AML. However, GSTM1 and GSTP1 polymorphisms did not influence the AML risk. Subjects carrying the GSTM1 Present, GSTT1 null and GSTP1 Ile / Val et Val /Val genotypes had a higher risk of developing AML. The results of meta-analysis showed a positive association between GSTM1 null, GSTT1 null and Ile105Val GSTP1 polymorphisms and AML risk in East Asians, Caucasians, and mixed populations, respectively. Conclusion: GST gene polymorphisms may be risk factors for acute myeloid leukemia.