Receptor Polymorphisms Research Articles

Genetic Polymorphism of TLR5 and TLP6 in Iraqi Patients with Heart Failure Disease

In spite of the high rate of morbidity and mortality heart failure (HF) is common, and none of the medications are now entirely available for HF treatment. In addition to many environmental influences and clinical diseases, genetic factors may also contribute to the progression and development of HF. In the current study, samples of blood were collected from 150 heart failure patients and 130 healthy controls. We evaluated the association of four single nucleotide polymorphisms (snps) of Toll-like receptors (TLR6 and TLR5) with (HF) susceptibility in the Iraqi population. In this work, (SNP) called Toll-like receptor 5 (rs5744168, rs2072493) and Toll-like receptor 6 (rs1039559, rs5743810) were employed. (PCR-RFLP) for snps (rs5744168, rs2072493, and re5743810), and sequencing for snps were used to assess the allele and genotype frequencies in both the patient and control groups (rs1039559). In patients with heart failure and healthy controls, a significant difference was discovered in the genotypic and allelic frequencies of snps. From our results, we suggest that these snps act as a potential predisposing factor for HF development.

Vitamin D and Autoimmune Rheumatic Diseases.

Vitamin D is a steroid hormone with potent immune-modulating properties. It has been shown to stimulate innate immunity and induce immune tolerance. Extensive research efforts have shown that vitamin D deficiency may be related to the development of autoimmune diseases. Vitamin D deficiency has been observed in patients with rheumatoid arthritis (RA) and has been shown to be inversely related to disease activity. Moreover, vitamin D deficiency may be implicated in the pathogenesis of the disease. Vitamin D deficiency has also been observed in patients with systemic lupus erythematosus (SLE). It has been found to be inversely related to disease activity and renal involvement. In addition, vitamin D receptor polymorphisms have been studied in SLE. Vitamin D levels have been studied in patients with Sjogren's syndrome, and vitamin D deficiency may be related to neuropathy and the development of lymphoma in the context of Sjogren's syndrome. Vitamin D deficiency has been observed in ankylosing spondylitis, psoriatic arthritis (PsA), and idiopathic inflammatory myopathies. Vitamin D deficiency has also been observed in systemic sclerosis. Vitamin D deficiency may be implicated in the pathogenesis of autoimmunity, and it may be administered to prevent autoimmune disease and reduce pain in the context of autoimmune rheumatic disorders.

Abstract 5951: The correlation between single nucleotide polymorphism of chemokine receptor and ligand and infiltrating immune cells on tumor microenvironment of gastric cancer

Abstract Objective: Chemokines play roles in many normal biological processes, such as hematopoietic cell genesis and leukocyte migration and homing. Chemokines could be responsible for eliciting local accumulation of immune cells within tumor microenvironment. In this study, we examine if genetic variations in chemokine receptor and ligand are associated with infiltrations of immune cells on tumor microenvironment in gastric cancer. Methods: In 356 gastric cancer patients who received curative surgery followed by adjuvant chemotherapy, total 105 single nucleotide polymorphisms (SNP) in a chemokine ligand and chemokine receptor locus within 16 genes (CXCR4, CXCR2, CXCR1, CX3CR1, CCR8, CCR9, CCR3, CCR2, CCR5, CCRL2, CCR6, CXCR5, CCR6, CXCR6, CCR7, DARC) were genotyped from peripheral blood sample. Total 11 immune markers such as CD3, CD4, CD8, FOXp3, CD68, CD163, L-selectin, i-NOS, ADMA17, Arginase, CD45RO were analyzed for deposition of immune cells according to SNP of chemokine receptor and ligand. Levels of immunohistochemistry staining were quantified by Image Analysis Toolbox and density of immune cells infiltration was calculated. Results: 32 SNP locus of 8 genes (such as CXCR1, CXCR2, CCR3, CCR2, CCR5, CCRL2, CCR6. CXCR5) were selected using 25% cut-off value of minor allele frequency (MAF). Among 8 genes, CCR5 was the most relevant gene for immune cell infiltration on tumor microenvironment. Intron1-2545G>A (rs1799987) were associated with increased accumulation of CD3+, CD68+ and FOXp3+ cells compared to recessive carriers of the common allele. In CCR5 SNP that contained the common alleles of intron1-2549 G>T (rs2734648) and exon2A-2081 A>G (rs1800023), CD3+, CD4+, CD8+ and FOXp3+ cells were infiltrated more than minor alleles. Conclusions: The associations between infiltration of immune cells and SNP of chemokine receptor and ligand in gastric cancer were shown. Particularly, CCR5 SNP may be most relevant for correlation with infiltration of immune cells on tumor microenvironment. Citation Format: Sunjoo Yoon, Ju Hyun Lee, Minsu Kang, Hyeon Jeong Oh, Jiwon Koh, Hye Seung Lee, So Hyun Kang, Young Suk Park, Keun-Wook Lee, Jin Won Kim. The correlation between single nucleotide polymorphism of chemokine receptor and ligand and infiltrating immune cells on tumor microenvironment of gastric cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5951.

Characterization of polymorphisms in the follicle-stimulating hormone receptor and insulin-like growth factor-1 genes and their association with fertility traits in Jawa-Brebes cows.

The availability of fertility markers is crucial for maintaining, protecting, and improving the genetics of Jawa-Brebes (Jabres) cows. Follicle-stimulating hormone receptor (FSHR) and insulin-like growth factor-1 (IGF-1) play critical roles in female reproductive physiology. The single-nucleotide polymorphisms (SNPs) FSHR G-278A and IGF-1 C-512T correlate with cows' fertility traits. This study aimed to identify these SNPs and their potential associations with fertility parameters in Jabres cows. Samples were collected from 45 heads of multiparous Jabres cows aged 3-10 years with body condition scores of 2.5-5.0 on a 5-point scale in Brebes Regency, Java, Indonesia. These cows were assigned to fertile (n = 16) and infertile groups (n = 29). Polymerase chain reaction (PCR) was carried out for DNA amplification of FSHR G-278A and IGF-1 C-512T fragments. Restriction fragment length polymorphism-PCR with the restriction enzymes FaqI for the product of FSHR G-278A and SnaBI for the product of IGF-1 C-512T was used to identify SNPs. The FaqI enzyme cut the 211 bp DNA fragment of FSHR G-278A in all samples into two bands of 128 bp and 83 bp (GG genotype). Meanwhile, the genotyping of amplicon products of IGF-1 C-512T generated a single 249 bp fragment (CC genotype) in both groups. The results showed that the FSHR G-278A/FaqI and IGF-1 C-512T/SnaBI loci were monomorphic in Jabres cows. Thus, neither FSHR G-278A/FaqI nor IGF-1 C-512T/SnaBI is a possible genetic marker for fertility in Jabres cows.

Glucocorticoid receptor polymorphism BclI with increased glucocorticoid sensitivity has a positive influence on quality of life in endogenous Cushing's syndrome in remission.

Patients with endogenous Cushing's syndrome (CS) may suffer from a wide range of neuropsychiatric symptoms leading to impaired quality of life (QoL). Glucocorticoid receptor (GR) polymorphisms are associated with increased (BclI and N363S) or decreased (A3669G and ER22/23EK) GR sensitivity. GR genotypes may modulate and affect QoL and recovery after remission differently via GR sensitivity. 295 patients with endogenous CS (81 active, 214 in remission) from 3 centers of the German Cushing's Registry were included for the cross-sectional analysis. All subjects were assessed with three questionnaires (CushingQoL, Tuebingen CD-25, SF-36). For the longitudinal part, 120 patients of them were analyzed at baseline and after 1.5 ± 0.9 yrs of follow-up. DNA samples were obtained from peripheral blood leukocytes for GR genotyping. Patients in remission scored significantly better than patients with active CS in the CushingQoL questionnaire and in the SF-36 sub-categories physical and social functioning, role-physical, bodily pain, and vitality. In cross-sectional analysis, no differences in QoL between minor allele and wildtype carriers were detected for all polymorphisms in active or cured CS. In longitudinal analysis, however, carriers with BclI minor allele showed significant improvement in SF-36 sub-categories vitality (P = .038) and mental health (P = .013) compared to wildtype carriers (active CS at baseline vs. CS in remission at follow-up). The outcome of the two questionnaires CushingQoL and Tuebingen CD-25 improved significantly in both wildtype and minor allele carriers. BclI minor allele carriers initially had the lowest QoL but recovered better from impaired QoL than wildtype carriers.

POLYMORPHISM OF GENES RESPONSIBLE FOR NEUROHUMORAL MECHANISMS OF DEVELOPMENT OF CHRONIC HEART FAILURE WITH PRESERVED EJECTION FRACTION IN PERSONS WITH TYPE 2 DIABETES MELLITUS

The search for genetic markers of chronic heart failure (CHF), comorbid with type II diabetes mellitus, is an urgent task. The study aim was to identify genetic polymorphisms associated with impaired neurohumoral regulation in patients with CHF with preserved and low ejection fraction and type II diabetes mellitus. Material and methods. Polymorphisms of genes responsible for neurohumoral mechanisms of CHF development were studied in 167 patients (69.9±10.1 years) with type II diabetes mellitus, hypertension, CHF with preserved or low ejection fraction, and healthy volunteers. Results and discussion. The angiotensin gene, angiotensin-converting enzyme, angiotensin 1 and 2 receptors polymorphisms are not involved in the CHF formation in patients with type II diabetes mellitus. In the control group, rs1403543 GA polymorphism was found in 90.48% of the examined, in patients with CHF with preserved ejection fraction and type II diabetes mellitus, GA and AA variants were found in 20% of cases, in the CHF group with a low ejection fraction AA polymorphism was found in 53.85% of the examined. It is possible they do not participate in the formation of CHF in patients with type II diabetes mellitus, or have a protective effect. The gene GNB: 825 C > T rs5443 polymorphism was detected from 53.33 to 61.9% of the examined in all groups. rs1799998 polymorphism is not associated with the development of CHF. The rs2070744 polymorphism is associated with the development of CHF with a preserved ejection fraction, but not CHF with a low ejection fraction, in patients with type II diabetes mellitus. The gene NOS3: 894 G > T rs1799983 in heterozygous and homozygous variants polymorphism was more common in patients with CHF with preserved ejection fraction (statistically insignificant). Conclusions. CHF with a preserved ejection fraction and CHF with a low ejection fraction in patients with type II diabetes mellitus are associated with different polymorphisms and have different pathogenesis. The gene AGTR2 polymorphism rs1403543 in patients with type II diabetes mellitus and CHF with preserved ejection fraction occurs less frequently than in the control group. The gene GNB polymorphism rs5443 in patients with CHF with a preserved ejection fraction and CHF with a low ejection fraction occurs much less frequently than in the control group. The gene NOS3 polymorphism rs2070744 in patients with CHF with a preserved ejection fraction occurs significantly more often than in the control group and in patients with CHF with a low ejection fraction.

Frequency of rs2228570 single nucleotide polymorphism of Vitamin-D Receptor (VDR) gene among the Kazakh ethnic group

The article presents the results of the study of vitamin D receptor (VDR) gene rs2228570 single nucleotide polymorphism (SNP) genotypes and individual alleles frequency among the Kazakh ethnic group representatives living in the Karaganda region. This SNP was determined by real-time polymerase chain reaction using TaqMan technology. The study relevance is due to the fact that genetic variations in rs2228570 affect the synthesis of the VDR protein and its activity as a transcription factor that regulates the expression of other genes. This mechanism determines the association of individual rs2228570 genotypes or alleles with susceptibility, course, and outcomes of various diseases. The polymorphism frequency may be depending on ethnicity. According to the study results, the most common genotypes of rs2228570 SNP among the Kazakhs were AG (32.8 %) and GG (25.2 %). The rarest are homozygotes TT (1.7 %) and CC (0.8 %). The frequency of all rs2228570 alleles was detected simultaneously in the present study for the first time. G became the predominant allele (51.3 %), less common was A (31.0 %), and the C and T alleles were the rarest (11.8 % and 5.9 %, respectively). The potential value of this SNP further study as a possible factor influencing the body’s susceptibility to various diseases, including COVID-19, is shown.

Association of the ADORA2A receptor and CD73 polymorphisms with epilepsy.

Single-nucleotide polymorphisms are connected with the risk of epilepsy on occurrence, progress, and the individual response to drugs. Progress in genomic technology is exposing the complex genetic architecture of epilepsy. Compelling evidence has demonstrated that purines and adenosine are key mediators in the epileptic process. Our previous study found the interconnection of P2Y12 receptor single-nucleotide polymorphisms and epilepsy. However, little is known about the interaction between the purine nucleoside A2A receptor and rate-limiting enzyme ecto-5'-nucleotidase/CD73 and epilepsy from the genetic polymorphism aspect. The aim of the study is to evaluate the impact of A2AR and CD73 polymorphisms on epilepsy cases. The study group encompassed 181 patients with epilepsy and 55 healthy volunteers. A significant correlation was confirmed between CD73 rs4431401 and epilepsy (p < 0.001), with TT genotype frequency being higher and C allele being lower among epilepsy patients in comparison with healthy individuals, indicating that the presence of the TT genotype is related to an increased risk of epilepsy (OR = 2.742, p = 0.006) while carriers of the C allele demonstrated a decreased risk of epilepsy (OR = 0.304, p < 0.001). According to analysis based on gender, the allele and genotype of rs4431401 in CD73 were associated with both male and female cases (p < 0.0001, p = 0.026, respectively). Of note, we found that A2AR genetic variants rs2267076T>C (p = 0.031), rs2298383C>T (p = 0.045), rs4822492T>G (p = 0.034), and rs4822489T>G (p = 0.029) were only associated with epilepsy in female subjects instead of male. It is evident that the TT genotype and T allele of rs4431401 in CD73 were genetic risk factors for epilepsy, whereas rs2267076, rs2298383, rs4822492, and rs4822489 polymorphisms of the A2AR were mainly associated with female subjects.

Study of the polymorphism of the ADRB2 molecular structure and its influence on the development of chronic postsurgical pain in children

Introduction. Pain is a signal to any aggression that leads to cellular damage and requires a defensive response. Uncontrolled acute perioperative visceral pain can lead to the development of pain chronicity. By studying the characteristics of chronic pain, some scientists have identified relationships with single-nucleotide polymorphisms of the beta2-adrenergic receptor (ADRB2) gene. Purpose - to study the dependence of pain expression in the postoperative period in children on the polymorphism of the molecular structure of the ADRB2 receptor. Materials and methods. The study involved 42 children (20 boys and 22 girls) aged 7 to 18 years who were treated in the surgical department in 2020-2022 for acute appendicitis and peritonitis. Results. Based on the results of examining all the subjects under study, 13 children had the Arg16Gly polymorphism, 15 children had the Arg16Gly polymorphic variant, and 14 children were diagnosed with the homomorphic Gly16Gly polymorphism in the ADRB2. The data obtained confirmed the trend of the preliminary analysis and proved better body response to pain relief and reduced pain intensity in individuals with the Arg16Arg variant of the ADRB2. Analysis of the dependence between the polymorphism of the ADRB2 molecular structure and Visual Analogue Scale (VAS) scores in children in the postoperative period proved that the presence of Arg in the receptor phenotype had a strong negative correlation with the VAS score on discharge day (r=-0.822, p&lt;0.001), while the presence of Gly in the receptor phenotype had a strong positive correlation with the Visual Analogue Scale score on discharge day (r=0.814, p&lt;0.001). In regression analysis, the presence of Gly in the receptor phenotype was associated with a 1.917-fold increase in the VAS score at hospital discharge (OR: 1.917; 95% CI: 1.448-2.385; р&lt;0.001). Conclusions. The presence of the homomorphic Arg16Arg variant of the ADRB2 in children who underwent anterior abdominal wall surgery was accompanied by rapid response to analgesics. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Detection and treatment of skin infection with Staphylococcus aureus in children with atopic dermatitis

Introduction. Atopic dermatitis is a common chronic relapsing inflammatory multifactorial skin disease. Staphylococcus aureus skin colonization increases during disease outbreaks and correlates with the severity of skin symptoms. Purpose - to evaluate the effectiveness of thyrothricin gel as an adjuvant therapy in the treatment of atopic dermatitis and the influence of polymorphisms of pattern recognition receptors on the achieving a therapeutic effect. Materials and methods. This study included patients with atopic dermatitis (n=37) aged 2-18 years from the Allergy Department of the Kyiv City Children’s Clinical Hospital No. 2. Patients were devided into two groups: a group that received thyrothricin gel on the affected skin areas 2 times a day for 7 days (the Group A) and a control group (the Group B) that received only basic symptomatic therapy. SCORAD (SCORing AD) and CDLQI (Children’s Quality of Life Index in Dermatology) scores were recorded before and after treatment, side effects were recorded during the study. Skin swabs were taken in the Group A before and after treatment. Genotyping of polymorphisms rs4696480 in the TLR2 gene, rs7309123 in the Dectin-1 gene were performed using polymerase chain reaction. Results. In both groups of children, improvement was observed in 7 days after treatment (p&lt;0.001). In the Group A, the improvement in ΔSCORAD was 16.6±5.9 points, in the Group B - 8.1±4.5 points. The difference in ΔSCORAD scores between the Groups A and B was statistically significant (W=225.0, p&lt;0.001). The decrease in CDLQI score after treatment was 3.8±1.8 points in the Group A and 2.3±1.25 points in the Group B. A significant decrease in CDLQI score was demonstrated in the intervention group than in the control group after treatment (W=275.5, p=0.004). After treatment, a bacteriological examination of the skin demonstrated the eradication of Staphylococcus aureus: in the Group A, 94.4% of patients were Staphylococcus aureus-negative. Polymorphisms rs4696480 in the TLR2 gene and rs7309123 in the Dectin-1 gene did not affect the speed of achieving the therapeutic effect. Conclusions. The addition of thyrothricin to standard therapy for atopic dermatitis in children with Staphylococcus aureus infection of affected skin may provide significant clinical benefit in SCORAD and CDLQI scores. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patients was obtained for conducting the studies. No conflict of interests was declared by the author.

Lack of Association between a Functional Polymorphism in Dopamine and Opioid Receptor Genes with Alcoholism in South Indian Tamilian Population.

Background: Single nucleotide polymorphism (SNP) of dopamine receptor (DRD2) and μ opioid receptor (OPRM1) genes are associated with susceptibility towards alcoholism. Hence, our study aimed to investigate the association of rs1799732 (DRD2) and rs1799971(OPRM1) with the risk of alcohol dependence in the south Indian Tamilian population and to compare the frequencies of these SNPs with major global populations. Methods: A total of 150 alcohol-dependent cases aged between 18 and 65 years who satisfied DSM-V were recruited from a de-addiction center (TTK hospital, Chennai). For the control group, 150 unrelated male blood donors with an AUDIT score of less than 8 were included. Genomic DNA was extracted and the alleles were genotyped using Taqman SNP genotyping assays by quantitative PCR. Results: Minor allele frequency (MAF) of rs1799732 and rs1799971 among controls were 16.7% and 50.3% respectively. Fisher’s exact test showed a highly significant difference in MAF of DRD2 and OPRM1 between south Indian controls and European as well as African populations. All the five genetic models of SNPs were evaluated using the Chi-square test revealed no statistically significant association between the SNPs and alcohol dependence. Conclusions: The present study did not find any association between DRD2 −141C Ins/Del and A118G OPRM1 polymorphism with alcoholism in the Tamilian population of south India.

Correlation of Q223R and K109R polymorphisms in leptin receptor gene with susceptibility of breast cancer: A systematic review and meta-analysis.

Increasing evidence has suggested a strong association of Q223R (rs1137101) and K109R (rs1137100) polymorphisms in leptin receptor (LEPR) gene with susceptibility of breast cancer (BC), but inconsistent results were obtained. To provide a quantitative assessment of this association, a systematic review and meta-analysis was performed. A literature search of PubMed, EMBASE, Google Scholar, and the Chinese National Knowledge Infrastructure was collected. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. A total of 20 case-control studies for Q223R polymorphism and 8 case-control studies for K109R polymorphism were included. Significant association between Q223R polymorphism and BC risk was not found in total, Asian or Caucasian population, but in African population: allelic model, OR = 0.72, 95% CI = 0.60-0.86, p < 0.001; recessive model, OR = 0.67, 95%CI = 0.52-0.87, P = 0.003; dominant model, OR = 1.58, 95% CI = 1.15-2.17, p = 0.004; homozygous model, OR = 0.51, 95% CI = 0.36-0.78, p < 0.001. Significant association between K109R polymorphism and BC risk was not found in total or Caucasian population, but in Asian population: dominant model, OR = 0.24, 95% CI = 0.07-0.84, p = 0.03; heterozygous model, OR = 1.87, 95% CI = 1.07-3.26, p = 0.03. The available evidence suggests that Q223R polymorphism may be significantly associated with BC risk in African population. K109R polymorphism may be significantly associated with BC risk in Asian population.

Endocannabinergic modulation of central serotonergic activity in healthy human volunteers

BackgroundThe serotonergic and the endocannabinoid system are involved in the etiology of depression. Depressive patients exhibit low serotonergic activity and decreased level of the endocannabinoids anandamide (AEA) and 2-arachidonylglycerol (2AG). Since the cannabinoid (CB) 1 receptor is activated by endogenous ligands such as AEA and 2AG, whose concentration are controlled by the fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase, respectively, we investigated the effects on serotonergic utilization. In this study, we investigated the impact of the rs1049353 single-nucleotide polymorphism (SNP) of the cannabinoid receptor 1 (CNR1) gene, which codes the endocannabinoid CB1 receptor, and the rs324420 SNP of the FAAH gene on the serotonergic and endocannabinoid system in 59 healthy volunteers.MethodsSerotonergic activity was measured by loudness dependence of auditory-evoked potentials (LDAEP). Plasma concentrations of AEA, 2AG and its inactive isomer 1AG were determined by mass spectrometry. Genotyping of two SNPs (rs1049353, rs344420) was conducted by polymerase chain reaction (PCR) and differential enzymatic analysis with the PCR restriction fragment length polymorphism method.ResultsGenotype distributions by serotonergic activity or endocannabinoid concentration showed no differences. However, after detailed consideration of the CNR1-A-allele-carriers, a reduced AEA (A-allele-carrier M = 0.66, SD = 0.24; GG genotype M = 0.72, SD = 0.24) and 2AG (A-allele-carriers M = 0.70, SD = 0.33; GG genotype M = 1.03, SD = 0.83) plasma concentration and an association between the serotonergic activity and the concentrations of AEA and 2AG has been observed.ConclusionsOur results suggest that carriers of the CNR1-A allele may be more susceptible to developing depression.

Impact of FCGR2A R131H, FCGR3A F158V and FCGR3B NA1/NA2 polymorphisms on response to fc-containing TNF inhibitors in Tunisian rheumatoid arthritis patients.

Single nucleotid polymorphisms (SNPs) of Fc-gamma receptors (FcgRs), by inducing a variation of their affinity to the Fc-region of immunoglobulins, might influence the efficacy of Fc-containing biologics prescribed in rheumatoid arthritis (RA). Our aim was to investigate associations of FCGR2A, FCGR3A and FCGR3B SNPs with TNF-inhibitors (TNFi)' response in Tunisian RA patients. A cross-sectional, observational and analytic multicentric cohort study was conducted in a group of 47 Tunisian RA patients treated with (etanercept [ETA], adalimumab [ADL] and infliximab [IFX]). Treatment outcome was evaluated after 6months. R131H-FCGR2A, F158V-FCGR3A and NA1/NA2-FCGR3B SNPs were genotyped. The analytic study including all types of TNFi showed that FCGR3A-F/F low-affinity receptor was associated with a greater decrease of DAS28, while FCGR3B-NA1/NA1 high-affinity receptor was associated with a lower decrease of DAS28 in ADL group. Furthermore, both of high affinity receptors FCGR3B-NA1/NA1 and FCGR3A-V/V were more prevalent in non-responders to ADL, according to EULAR criteria. Identifying reliable biomarkers of response to biologics in RA is necessary to improve responsiveness, preserve joints' functions and structure, and reduce treatment's cost. Our study showed that FCGR3A and FCGR3B polymorphisms might have an impact on TNFis' response in RA Tunisian patients since bad response was more frequent in homozygous carriers of high affinity alleles FCGR3A-V and FCGR3B-NA1.

Potential Impact of Polymorphisms in Toll-like Receptors 2, 3, 4, 7, 9, miR-146a, miR-155, and miR-196a Genes on Osteoarthritis Susceptibility.

Osteoarthritis (OA) is a progressive inflammatory disease of synovial joints and a leading cause of disability among adults. Inflammation-related genes, including genes for Toll-like receptors (TLRs), are tightly controlled by several microRNAs that, in addition to their pivotal role in the epigenetic regulation of target genes, are ligands for TLR activation and downstream signaling. Thus, we evaluated the association between OA risk and genetic variants in TLR2, TLR3, TLR4, TLR7, TLR9, and microRNAs that regulate TLRs signaling miR146a, miR155, and miR196a2. Our study group consisted of 95 surgically treated OA patients and a control group of 104 healthy individuals. Genetic polymorphisms were determined using TaqMan real-time PCR assays (Applied Biosystems). Adjusted logistic regression analysis demonstrated that polymorphisms in TLR4 rs4986790 (OR = 2.964, p = 0.006), TLR4 rs4986791 (OR = 8.766, p = 0.00001), and TLR7 rs385389 (OR = 1.579, p = 0.012) increased OA risk, while miR-196a2 rs11614913 (OR = 0.619, p = 0.034) was significantly associated with decreased OA risk. Our findings indicate that polymorphisms in the TLR4 and TLR7 genes might increase OA risk and suggest a novel association of miR-196a2 polymorphism with decreased OA susceptibility. The modulation of TLRs and miRNAs and their cross-talk might be an attractive target for a personalized approach to OA management.

Vitamin D and Multiple Myeloma: A Scoping Review

As the global incidence of multiple myeloma (MM) increases, the identification of modifiable risk factors for disease prevention becomes paramount. Maintaining optimal vitamin D status is a candidate for prevention efforts, based on pre-clinical evidence of a possible role in disease activity and progression. A structured scoping review was performed to identify and describe human-level research regarding the association between vitamin D and MM risk and/or prognosis. Searches of three databases (OVID-Medline, OVID-Embase, and OVID-Cochrane Library) yielded 15 included publications. Vitamin D deficiency is fairly common among patients with MM, with 42.3% of participants in the studies identified as having a vitamin D deficiency. No included publication reported on vitamin D status and the risk of developing or being newly diagnosed with MM. Possible associations with vitamin D that warrant future exploration include the incident staging of MM disease, the occurrence of peripheral neuropathy, and survival/prognosis. Vitamin D receptor (VDR) polymorphisms associated with MM also warrant further investigation. Overall, this scoping review was effective in mapping the research regarding vitamin D and MM and may help support new hypotheses to better describe this association and to better address identified knowledge gaps in the literature.

Genetic variation in salt taste receptors impact salt intake and blood pressure

So far, few studies have examined the effect of salt taste receptors genetic variation on dietary intake in the Iranian population. We aimed to evaluate associations between single nucleotide polymorphisms (SNPs) in salt taste receptors’ genes with dietary salt intake and blood pressure. A cross-sectional study was carried out among 116 randomly selected healthy adults aged ≥ 18 in Isfahan, Iran. Participants underwent sodium intake determination by 24-h urine collection, as well as dietary assessment by semi-quantitative food frequency questionnaire and blood pressure measurement. Whole blood was collected to extract DNA and genotype of SNP rs239345 in SCNN1B and rs224534, rs4790151 and rs8065080 in TRPV1 gene. Sodium consumption and diastolic blood pressure were significantly higher in carriers of the A-allele in rs239345 compared to subjects with the TT genotype (4808.4 ± 824.4 mg/day vs. 4043.5 ± 989.3 mg/day; P = 0.004) and 83.6 ± 8.5 mmHg vs. 77.3 ± 7.3 mmHg; P = 0.011), respectively. The level of sodium intake was lower in the TT genotype of TRPV1 (rs224534) than the CC genotype (3767.0 ± 713.7 mg/day vs. 4633.3 ± 793.5 mg/day; P = 0.012). We could not find any association between genotypes of all SNPs with systolic blood pressure as well as genotypes of rs224534, rs4790151 and rs8065080 with diastolic blood pressure. Genetic variations can relate with salt intake and consequently may associate with hypertension and finally cardiovascular disease risk in the Iranian population.

Interactions of Vitamin D Receptor Polymorphisms with Hypertriglyceridemia and Obesity in Chinese Individuals Susceptible to Hypertension and Diabetes Comorbidity

Interactions of Vitamin D Receptor Polymorphisms with Hypertriglyceridemia and Obesity in Chinese Individuals Susceptible to Hypertension and Diabetes Comorbidity

The effect of ACE2 receptor, IFN-γ, and TNF-α polymorphisms on the severity and prognosis of the disease in SARS-CoV-2 infection.

To investigate the effect of genetic variations in the angiotensin converting enzyme (ACE), interferon (IFNG) and tumor necrosis factor (TNF-α) genes on the severity of coronavirus disease (COVID-19). Between September and December 2021, 33 patients with COVID-19 were included in this prospective study. The patients were classified and compared according to disease severity: mild&moderate (n = 26) vs severe&critical (n = 7). These groups were evaluated to assess possible relationships with ACE, TNF-α and IFNG gene variations using univariate and multivariable analyses. The median age of the mild&moderate group was 45.5 (22-73), and that of the severe&critical group was 58 (49-80) years (p = 0.014). Seventeen (65.4%) of the mild&moderate patients and 3 (42.9%) of severe&critical patients were female (p = 0.393). According to results of univariate analysis, the percentage of patients with the c.418-70C>G variant of the ACE gene was significantly higher in the mild&moderate group (p = 0.027). The ACE gene polymorphisms, c.2312C>T, c.3490G>A, c.3801C>T, and c.731A>G, were each only seen in separate patients with critical disease. The following variants were observed more frequently in the mild&moderate group: c.582C>T, c.3836G>A, c.511+66A>G, c.1488-58T>C, c.3281+25C>T, c.1710-90G>C, c.2193A> G, c.3387T>C for ACE; c.115-3delT for IFNG; and c.27C>T for TNF. It can be expected that patients carrying the ACE gene c.418-70C>G variant may present with a mild clinical manifestation of COVID-19. Several genetic polymorphisms may be associated with pathophysiology, as they appear to help predict COVID-19 severity and enable early identification of the patients requiring aggressive treatment.

Vitamin D Receptor Polymorphisms Among the Turkish Population are Associated with Multiple Sclerosis.

Multiple sclerosis (MS) is an inflammatory disease characterized by demyelination and axonal degeneration affecting the central nervous system. Among the genetic factors suggested to be associated with this disease are polymorphisms to the vitamin D receptor (VDR) gene. We tested the hypothesis that polymorphisms in the vitamin D receptor (VDR) gene are associated with MS. The aim of the study was to investigate the relationship of MS with the VDR gene Fok-I, Bsm-I and Taq-I polymorphisms among the Turkish population. This study contains 271 MS patients and 203 healthy controls. Genomic DNA was isolated from the samples and the VDR gene Fok-I, Bsm-I and Taq-I polymorphism regions were amplified by polymerase chain reaction (PCR). The PCR products were digested, and the genotypes were determined based on size of digested PCR products. Our results demonstrate associations between MS and the distribution of the VDR gene Fok-I T/T polymorphism genotype in a dominant model, VDR gene Fok-I T allele frequency, distribution of VDR gene Taq-I C/C polymorphism genotype in a dominant model and VDR gene Taq-I C allele frequency (Pearson test, p<0.05). However, there was no association between MS and the VDR gene Bsm-I polymorphisms for the genotype distribution (Pearson test, p>0.05) or allele frequency (Pearson test, p>0.05). Fok-I and Taq-I VDR gene polymorphisms are significantly associated with MS in dominant, homozygote and heterozygote inheritance models among the Turkish population.