Receptor Polymorphisms Research Articles

Toll-like receptors polymorphisms and COVID-19: a systematic review.

COVID-19 is a disease caused by SARS-CoV-2. It became a health problem affecting the lives of millions of people. Toll-like receptors are responsible for recognizing viral particles and activating the innate immune system. The genetic factors associated with COVID-19 remain unclear. Thus, this study aims to assess the association between the polymorphism in Toll-like receptors and susceptibility to COVID-19. We searched the electronic databases (Science Direct, PUBMED, Web of Science, and Scopus) for studies assessing the association between Toll-like receptor polymorphisms and susceptibility to COVID-19. The quality of the studies was assessed using the Q-Genie tool. Thirteen studies were included in this systematic review. The studies analyzed polymorphisms in TLR2, TLR3, TLR4, TLR7, TLR8 and TLR9. We used SNP2TFBS bioinformatic analysis to identify the variants influencing transcription factor binding sites. The Ensembl Genome Browser was used to assess the allele and genotype frequencies in different populations. The bioinformatic analysis revealed that the variant rs5743836 of TLR9 affects the transcription factor binding sites NFKB1 and RELA. The genotype frequency of the variants rs3775291, rs3853839, rs3764880 were higher in East Asian population compared to the other populations. The frequency of the rs3775290 variant was higher in East and South Asian populations. The rs179008 variant was higher in the European population, and the rs5743836 was higher in the African population. Toll-like receptors play an important role in COVID-19 susceptibility. Further studies in different populations are necessary to elucidate the role of Toll-like receptors polymorphisms in SARS-CoV-2 infection.

Stone recurrence among Indonesian kidney stone formers: a comprehensive analysis of genetic polymorphism, demographic, and clinical factors

BACKGROUND The recurrence rate of kidney stone disease (KSD) can exceed 50% within 5 years. This study aimed to investigate factors associated with stone recurrence based on single nucleotide polymorphisms (SNPs) of the calcium-sensing receptor (CaSR) rs1801725 and rs1042636, demographic, and clinical profiles. METHODS We collected data on the demographic and clinical characteristics of 80 adult kidney stone formers from April 2021 to September 2022, including peripheral blood samples, morning and 24-hour urine, and 7-day water intake records. Real-time polymerase chain reaction was used to evaluate SNP. Comparisons were made between patients with recurrent and first-time stones. RESULTS 41% of 80 patients have experienced stone recurrence. Recurrent stone formers exhibited significantly higher 24-hour urine calcium excretion (p = 0.03) and lower serum calcium levels (p = 0.019) than first-time stone formers. Hypocitraturia (100%), low urine volume (78%), and hyperoxaluria (55%) were the main abnormalities of all patients. No significant differences were found in CaSR gene polymorphisms and other demographic, biochemical, or clinical parameters. CONCLUSIONS Recurrent stone formers had higher 24-hour urine calcium excretion and lower serum calcium levels. Other risk factors and CaSR polymorphisms may insignificantly affect KSD recurrence.

A review of vitamin D deficiency and vitamin D receptor polymorphisms in endocrine related disorders.

The endocrine system is a complex network of glands that produce and release hormones that regulate various physiological processes. In the past few decades, the human skin has been identified as an important peripheral endocrine organ that is the main site for the synthesis of vitamin D through exposure to sunlight. Mutations in downstream vitamin D-related gene pathways are associated with disease development. The vitamin D receptor (VDR) gene, which regulates the pleiotropic effects of vitamin D, has been extensively studied in adult populations. Several studies have reported the prevalence of vitamin D deficiency in children and adolescents. With changes in socioeconomic status and lifestyle, vitamin D-deficient individuals are prone to developing the disease at a young age. However, geographical and racial differences affect the association between VDR gene polymorphisms and vitamin D endocrine disorders, explaining the non-consensus effects of polymorphisms and their association with disease development across populations. In this review, we discuss the connection between the vitamin D endocrine system and polymorphisms in the gene encoding VDR in children and adolescents, focusing on its effects on growth, puberty, insulin resistance, and the immune system.

Genetic Polymorphism of Toll-Like Receptor 4 Gene (rs4986791) among Adult Patients with Acute Myeloid Leukemia

Genetic Polymorphism of Toll-Like Receptor 4 Gene (rs4986791) among Adult Patients with Acute Myeloid Leukemia

New ways to repurpose salmeterol in an animal model of fibromyalgia.

Fibromyalgia (FM) is a syndrome of pervasive chronic pain accompanied by low mood, sleep disorders, and cognitive decline. The dysfunction of central pain processing systems along with neurotransmitter disturbances are possible contributing mechanisms. Genetic polymorphism of the 𝛽2 adrenergic receptors is reported in FM patients. It is reported that chronic β2 agonists administration is effective for neuropathic pain alleviation. No current information, however, exists on their potential to alleviate nociplastic pain, such as FM. Therefore, the purpose of the current study is to examine salmeterol's potential antiallodynic effects in experimentally produced FM and explore some of the possible contributing mechanisms. Thirty rats are allocated into three groups (n = 10): a normal group, a reserpine group that received reserpine (1 mg/kg; s.c.) for 3 days, and a reserpine + salmeterol group that received salmeterol (1 mg/kg; i.p.) for 21 consecutive days following last reserpine injection. Reserpine administration resulted in behavioral and biochemical changes consistent with FM, including thermal and mechanical hyperalgesia, depressive behavior, and motor incoordination. This is coupled with disturbed spinal monoamine levels, depressed cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling, disturbed mitochondrial function/dynamics, and compromised blood-nerve barrier integrity. Treatment with salmeterol conceivably reversed these effects. β2 receptor agonists such as salmeterol could be regarded as a promising strategy for the management of FM.

Association of ACE2 Gene Variants with Adverse Perinatal Outcomes in COVID-19 Infected Pregnant Women in Kazakhstan

SARS-CoV-2 utilizes the angiotensin-converting enzyme 2 (ACE2) receptors located on membranes to enter host cells. Nevertheless, the ACE2 gene primarily encodes for a zinc metalloproteinase, which is a part of the renin–angiotensin system (RAS). ACE2 downregulation results in the deregulation of RAS in favor of pro-fibrosis, pro-apoptosis, oxidative stress, pro-inflammation, aldosterone production and release, and blood vessel contraction axis. ACE2 is highly expressed in the placenta. There are both axes of the RAS system in the placenta. This study aims to assess the perinatal outcomes with ACE2 receptor polymorphisms in pregnant women infected with SARS-CoV-2 during pregnancy. The case-control study was conducted to determine the association of ACE2 single-nucleotide polymorphisms in 171 COVID-19-positive pregnant subjects and 112 control subjects. The recessive mutations of rs2158082 and rs4830974 were associated with an increased risk of low birthweight and preterm birth, whereas the dominant mutation of rs2285666 (CT + TT) was associated with decreased odds of low birthweight. COVID-19 was not a significant factor contributing to the adverse perinatal outcomes in our sampling. These findings may help to clarify the controversy regarding the increased risk of adverse perinatal outcomes observed during COVID-19 as well as provide new perspectives for research on the genetic factors associated with a higher risk of adverse perinatal outcomes.

The association of gene polymorphisms of adenosine and dopamine receptors with the response to caffeine citrate treatment in infants with apnea of prematurity: a prospective nested case-control study

BackgroundTo investigate the potential influence of adenosine and dopamine receptor genes polymorphisms in combination with clinical factors on the response of preterm infants to caffeine citrate treatment in apnea of prematurity (AOP).MethodsA prospective nested case-control study enrolled 221 preterm infants with gestational age < 34 weeks. These infants were divided into the response (n = 160) and the non-response groups (n = 61). 22 single-nucleotide polymorphisms in adenosine and dopamine receptor genes were genotyped. The basic characteristics and clinical outcomes of the two groups were compared. Univariate logistic regression analysis was performed to evaluate the differences in genotype distribution between the groups. Multivariable logistic regression analysis was performed to identify independent risk and protective factors and develop a nomogram to predict caffeine citrate response in preterm infants.ResultsPreterm infants in the non-response group had lower gestational age, lower birth weight, longer periods of oxygen supplementation and caffeine citrate use, and higher incidence of patent ductus arteriosus (PDA), bronchopulmonary dysplasia (BPD), neonatal respiratory distress syndrome (NRDS), retinopathy of prematurity (ROP), and brain injury (P < 0.05 for all). The ADORA1 rs10920573, ADORA2B rs2015353, ADORA3 rs10776728, DRD3 rs7625282, and DRD3 rs6280 gene polymorphisms were associated with caffeine citrate response in preterm infants (PFDR < 0.05 for all). The ADORA1 rs10920573 CC (aOR, 3.51; 95% CI, 1.34–9.25) and DRD3 rs6280 CT genotypes (aOR, 3.19; 95% CI, 1.53–6.65) were independent risk factors for non-response, whereas greater gestational age (aOR, 0.631; 95% CI, 0.53–0.75) was an independent protective factor for response. The concordance index of the nomogram was 0.764 (95% CI, 0.687–0.842), and the calibration and decision curve analysis indicated the nomogram had excellent predict performance.ConclusionsAdenosine receptor gene and dopamine receptor gene polymorphisms influence caffeine citrate treatment response in AOP. By combining genetic and clinical variables, it is possible to predict the response to caffeine citrate treatment in preterm infants.

Genetic Polymorphisms of Prokineticins and Prokineticin Receptors Associated with Human Disease

Prokineticins (PKs) are low molecular weight proteins that exert their effects by binding to two seven-transmembrane G-protein-coupled receptors (prokineticin receptors, PKRs). The prokineticin system is an important player in the development of various diseases. Several polymorphisms that are associated with infertility, neuroendocrine disorders, Hirschsprung’s syndrome (HSCR), idiopathic central precocious puberty (CPP) and congenital disorders such as Kallmann syndrome (KS) have been described for both the PKs and PKR genes. The aim of this study is to summarize and describe the impact of PK/PKR polymorphisms on the pathogenesis and outcome of the above diseases, highlighting the PK system as a therapeutic target and diagnostic biomarker in pathological conditions.

Analysis of angiotensin II type 1 receptor and osteoprotegerin gene polymorphism on the risk of cardiovascular mortality risk and progressivity of chronic kidney disease.

Chronic kidney disease (CKD) is a significant global public health issue with increased risk of atherosclerotic cardiovascular disease (ASCVD) and cardiovascular mortality. Single nucleotide polymorphisms (SNPs) on angiotensin II type 1 receptor (AT1R) A1166C and osteoprotegerin (OPG) C950T gene have received significant attention as a genetic risk factor for cardiovascular disease and CKD. This was a cross-sectional study involving 75 adults with CKD recruited from Nephrology Outpatient Clinics of Universitas Airlangga Hospital, Surabaya, Indonesia. Demographic data was obtained from interviews and medical records. The "CKD Patch" application was used to asses ASCVD and cardiovascular mortality risk scores. Statistical analysis was performed by using SPSS version 26. We detected four different AT1R gene polymorphisms (A1166C, A1160C, G1170T, and G1181C) and two OPG gene polymorphisms (T950C and G1181C) in Indonesian CKD patients. A1160C and G1181C polymorphisms were novel SNPs, newly discovered in this research. No significant association was found between AT1R SNPs and kidney prognostic markers or ASCVD risk/mortality risk scores. However, for OPG C950T we found that TT genotype had a significantly higher ACR than TC or CC genotype (P=0.032). As for OPG G1181C, we found that GG genotype had a higher serum creatinine and albumin to creatinine ratio compared to GC and CC genotypes (P=0.004 and 0.029, respectively). Genotype GC for OPG G1181C was also shown to be protective for having better kidney markers and lowest cardiovascular mortality risk compared to GG and CC genotypes (P=0.018 and 0.032, respectively). Increased ASCVD risk and mortality risk score was not found on individuals with AT1R gene SNPs. However, for OPG gene polymorphism, C950T and G1181C were associated with kidney progression and cardiovascular mortality.

Gene Polymorphism Of TNF-A (Rs1799964) In Aborted Women With Respiratory Disease In Al-Diwaniyah Province

Background: TNF-α, a proinflammatory cytokine, plays a significant role in the etiology of various illnesses. The encoding gene is found on chromosome 6's short arm in the major histocompatibility complex class III region. Polymorphisms in the TNF-α gene promoter region are believed to impact illness susceptibility and severity. This review summarizes the research on the association between TNF-α gene and receptor polymorphisms and respiratory illness development. This study aim to determine of gene polymorphism of TNF-α in aborted women with respiratory diseases. Methods : The study was carried out for 100 pregnant women, including 60 aborted women with and without respiratory diseases, and 40 women as healthy control group. Genotypes in TNF-α T&gt;C SNPs were identified using self- designed nested T-ARMS PCR tests. Sequencing validated randomly chosen PCR results that represented unique genotypes in TNF-α SNPs. Results : The results of TNF-α (rs1799964) C/T SNP genotyping between aborted women with respiratory diseases and healthy control revealed that the heterozygous C/T genotype was a significant risk factor with an OR of 6.28, while the homozygous TT genotype was non-significant (OR= 2.09). Conclusion : The rs1799964 TNF-α polymorphisms are possible genetic risk factors of respiratory diseases and might be its predictive markers.

Vitiligo: From mechanisms of disease to treatable pathways

AbstractVitiligo is a chronic autoimmune‐mediated disease characterised by the loss of pigmentary melanocytes in the epidermis. Vitiligo is associated with loss of functional epithelium and significant reductions in quality of life with limited long‐term treatment options, highlighting a continued unmet clinical need. A comprehensive understanding of the pathophysiology and newly investigated treatment pathways may guide multimodal treatment strategies and identify future drug targets. The pathology of vitiligo is multifactorial; however, environmental insults in genetically susceptible populations may lead to disease development. Autoreactive CD8+ T‐cells that target melanocytes and release inflammatory mediators, including interferon‐γ and interleukins 2, 6, 15, 17 and 33 among others, have been identified in vitiligo pathogenesis. Treatment modalities for vitiligo revolve around six broad disease concepts, including procedural modalities (tissue and cellular grafting), phototherapy, stem cells, anti‐inflammatories, genetic polymorphisms and antioxidants/vitamins/herbals. Genetic polymorphisms, such as catalase gene variations and toll‐like receptor polymorphisms, along with stem cell targets such as melanocytes derived from stem cells, have been implicated in vitiligo onset and possible treatment. Novel JAK‐STAT inhibitors have been recently investigated for vitiligo, whereas topical corticosteroids and calcineurin inhibitors continue to be used. Vitamin D, vitamin E, zinc, copper, piperine, pseudo catalase and other vitamins/herbals may improve vitiligo outcomes primarily through antioxidant supplementation pathways. Future studies should investigate alternative drug pathways and targets implicated in vitiligo in large patient cohorts, as well as treatments that target suspected causative immune cells, including memory T‐cells, which may provide long‐lasting disease‐free remission.

Association between some Serum Parameters in Iraqi Women with Polycystic Ovary Syndrome and leptin receptor gene polymorphism

Polycystic ovarian syndrome (PCOS) is considered as a complex, heterogeneous disorder that impacts 5-10% of women at reproductive age. This study aimed to evaluate the association of leptin recepter gene polymorphism (Lys109Arg, rs1137100) and some serum parameters with PCOS in of Iraqi women. This case-control study was carried out during the period from July to October, 2022 at Infertility Care and IVF center of Kamal AL-Samaraay Hospital, Baghdad. The study included 120 Iraqi women as a sample size divided into two groups 60 PCOS patients and 60 apparently healthy control. PCOS patients were diagnosed by gynecologists according to Rotterdam criteria. The genotypes of leptin receptor gene at rs137100 SNP were determined by using HRM-PCR. The serum levels of leptin, soluble leptin receptor (sOB-R) and AMH were measured by using Elisa kits. Lipid profile parameters were measured by spin 200 full auto. LH, FSH, testosterone, estradiol, progesterone, TSH, T3 and T4 hormones were measured by cobas E411. Results revealed that BMI values were significantly increased (p≤0.01) in PCOS patients compared to controls (30.21±0.70 versus 24.28±0.617). Serum leptin and sOB-R levels were significantly (p˂0.05) higher in PCOS patients than controls (4303.28±71.55 versus 3854.84 ±213.96 pg /ml and 144.09 ±5.51 versus 122.16 ±7.64 ng/ml respectively). The frequency of AA genotypes was significantly (p˂0.05) lower in PCOS patients than in apparently healthy subjects (33.3 % versus 65.0% respectively) whereas the frequencies of AG and GG genotypes were significantly (p˂0.05) higher in PCOS patients versus controls (53.3% versus 26.6% and 13.4% versus 8.4% respectively).The A allele frequency was higher in apparently healthy subjects than in PCOS women (78.3% versus 60.0% respectively) while G allele frequency was significantly higher in PCOS patients versus controls (80.0% versus 21.7%, respectively). It was concluded that the leptin receptor polymorphism (rs1137100) is strongly linked to an increased risk of developing PCOS. Further, those with the A allele are less likely to develop PCOS.

Vitamin D receptor polymorphisms associate with the efficacy and toxicity of radioiodine-131 therapy in patients with differentiated thyroid cancer.

Radioiodine-131 (I-131) therapy is the common postoperative adjuvant therapy for differentiated thyroid cancer (DTC) However, methods to evaluate the efficacy and toxicity of I-131 on DTC are still lacking. To evaluate the association between vitamin D receptor (VDR) gene polymorphisms and the efficacy and toxicity of I-131 in DTC patients. A total of 256 DTC patients who received I-131 therapy were enrolled. The patients were divided into effective group and ineffective group. 4 single nucleotide polymorphisms (SNPs) (rs7975232, rs731236, rs1544410 and rs10735810) of VDR were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) Cell counting kit-8 (CCK-8) and flow cytometry were used to detect the proliferation and apoptosis of thyroid cancer cells. Patients in effective group had more CC genotype of rs7975232 and GG genotype of rs10735810 compared with patients in ineffective group They were also independent factors for influencing the efficacy of I-131. PTC-1 and FTC-133 cells transfected with CC genotype of rs7975232 showed lower proliferative activity and higher apoptosis rate after being treated with I-131 In addition, patients with CC genotype at rs7975232 had fewer adverse reactions after I-131 treatment. VDR gene polymorphisms may be associated with the efficacy and toxicity of I-131 in DTC patients, which will help to personalize the treatment for patients.

Significance of FSHR and LHCGR gene polymorphisms on clinical outcomes in gonadotropin-releasing hormone antagonist protocol with freeze-all strategy: A case-control study.

Follicle-stimulating hormone receptor (FSHR) and luteinizing hormone/choriogonadotropin receptor (LHCGR) are integral to ovarian function, facilitating follicle development and maturation through their respective hormonal interactions. The influence of receptor polymorphisms on the outcomes of freeze-all cycles remains unclear. This study investigates the impact of FSHR N680S and LHCGR N312S polymorphisms on clinical outcomes in freeze-all cycles. Women undergoing controlled ovarian stimulation for assisted reproductive technology participated in this study. They were administered a gonadotropin-releasing hormone antagonist protocol, with recombinant follicle-stimulating hormone (rFSH) dosages adjusted according to age, body mass index, antral follicle count, and individual hormonal responses. Additionally, human menopausal gonadotropin dosages were tailored based on the LHCGR N312S genetic variant. Analysis revealed no significant differences in age, body mass index, antral follicle count, or marital status across the genotypes of FSHR N680S and LHCGR N312S. However, notable differences were observed in the rFSH dosage required daily and in total among the FSHR polymorphism genotypes. Genotypes of the LHCGR polymorphism correlated with fewer stimulation days. A significant interaction was observed between the 2 polymorphisms concerning total rFSH dosage. The presence of serine in the FSHR polymorphism was associated with higher rFSH dosage requirements. Both FSHR N680S and LHCGR N312S polymorphisms significantly influenced clinical pregnancy and live birth outcomes in freeze-all cycles, underscoring the potential of a pharmacogenomic approach to optimize hormone supplementation in controlled ovarian stimulation protocols during assisted reproductive technology treatments.

Inflammation and Vitamin D Receptor Polymorphism: Impact on All-Cause and Cardiovascular Mortality in Mexican Women on Dialysis.

Mineral bone disease (MBD) is common in dialysis patients. Genetics and the hormonal environment influence the clinical picture and outcomes of women. This study aimed to determine how these factors affect mortality. In 234 female dialysis patients on Continuous Ambulatory (48%) or Automated (29%) Peritoneal Dialysis or Hemodialysis (23%), MBD biochemical variables, as well as bone density and genetic Bsm1 polymorphism of vitamin D receptor (VDR) were performed at baseline. The cohort was followed-up by 17 (IQ range 15-31) months. According to VDR polymorphism, the distribution of patients was bb: 64% and BB+Bb: 36%. Fifty-five patients died from all-cause mortality; the hs-C-reactive protein level was the most significant risk in multivariate Cox analysis. Nineteen died from cardiovascular mortality. None of the variables were significant for cardiovascular mortality. Patients with bb plus inflammation had the highest risk in the analysis; the significance persisted after adjustment for age, diabetes, and parathyroid hormone levels HR 2.33 (95% CI, 1.01-8.33) and after further adjustment for time on dialysis, albumin, and Osteoprotegerin levels HR 3.49 (95% CI, 1.20-10.9). The presence of the bb genotype from VDR and inflammation had the highest risk of death from all-cause mortality in females on CAPD, APD, and HD patient.

Adenosine A2A signaling in mood disorders: How far have we come?

Over the years, evidence has continued to support the role of the adenosinergic system in shaping emotional behavior and its impact on the development of mood disorders. In the 1980s, pioneering studies revealed that tricyclic antidepressants could modulate the levels of adenosine and adenosine metabolism. Moreover, evidence from animal models support a regulation of adenosine receptors in brain regions involved in emotional responses, and the role of pharmacological manipulation of adenosine receptors on behavioral despair, anxiety, locomotion, rewards processing and cognition. Clinical research has focused on the effects of caffeine, a non-selective adenosine receptor antagonist, and in genetic polymorphisms in adenosine receptors on emotional regulation in psychiatric patients. Recently, the approval of Istradefylline as an adjunctive treatment for Parkinson's disease holds great promise to expand our understanding of adenosine A2A receptors (A2AR) blockade in humans. Furthermore, recent advancements in transgenic lines and optogenetic techniques have highlighted the role of adenosine receptors in specific cell types and brain circuits that control emotional behavior. In this review, our focus will be on A2AR, given their strong association to stress-related conditions, mood disorders, and the potential of A2AR antagonists in clinical research. We will discuss the progress achieved in understanding its role in emotional regulation, emphasizing functions across distinct cell types and potential applications as a pharmacological target for mood disorders in the upcoming years.

Low-Density Lipoprotein Receptor Apolipoprotein B Gene Polymorphism in Kurdish Patients With Severe Hypercholesterolemia.

Background Polymorphisms in the low-density lipoprotein receptor (LDLR) and apolipoprotein B 100 (APOB-100) genes have been linked to severe hypercholesterolemia in several populations. This study investigated the frequency of LDLR-Ava II and APOB-Xba I polymorphisms among Kurdish patients with severe hypercholesterolemia. Methodology We investigated LDLR-Ava II and APOB-Xba I gene polymorphisms in Kurdish patients attending the Duhok Specialized Laboratory Center in Duhok, Kurdistan Region, Iraq. We included a total of 80 subjects in this study, of which 40 (20 males and 20 females) had severe hypercholesterolemia, and 40 apparently healthy volunteers (21 males and 19 females) had normocholesterolemia, served as a control group. We used the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique to determine the polymorphisms of the LDLR-Ava II and APOB-Xba I genes. Results In those with severe hypercholesterolemia, the observed allele frequencies were AA LDLR-Ava II polymorphism (eight, 20%) followed by TT APOB-Xba I polymorphisms (six, 15%), whereas these frequencies were five (12.5%) and one (2.5%) in those with normocholesterolemia, respectively. The AA genotype group had considerably higher cholesterol and LDL-C levels compared with the GG genotype group. A similar pattern was observed when comparing the TT and CC genotype groups. Conclusions Our results showed a high frequency of AA LDLR-Ava II polymorphism in conjunction with TT APOB-Xba I polymorphism which may be strongly associated with hypercholesterolemia in the Kurdish population.

Follicle-stimulating hormone receptor gene polymorphisms influence Body Mass Index, metabolism, and bone mineral density in postmenopausal women.

Covering a significant part of a woman's life, the postmenopausal phase is often associated with the onset of obesity, metabolic dysfunction, osteoporosis, and their most disabling complications. In this context, scant evidence from both preclinical and clinical studies suggests that single nucleotide polymorphisms (SNPs) of the follicle-stimulating hormone receptor (FSHR) gene might be involved in the etiopathogenesis of these conditions, posing them as possible molecular predictors of their development. Therefore, this study aimed to evaluate the role of the FSHR gene SNPs c.2039A>G and c.-29 G>A on Body Mass Index (BMI), metabolic parameters, and bone metabolism in postmenopausal women. To achieve this goal, 49 postmenopausal Caucasian women aged from 45 to 80 years and with no factors known to influence metabolism and/or bone mineral density (BMD) were enrolled and assessed for their medical history, medical family history, anthropometric parameters and hormonal, metabolic and lipid profiles, and BMD. Then, they were genotyped for the FSHR gene SNPs c.2039A>G and c.-29G>A. Finally, the resulting data were classified according to woman's genotypes and subjected to statistical analysis. No significant differences were found between the distributions of most endpoint parameters examined by genotype. However, none of the women with the c.2039A>G FSHR GG gene SNP were affected by obesity and had the highest lumbar BMD z-score within the cohort. Additionally, those with the FSHR c.-29G>A AA genotype had the lowest serum glucose levels. This preliminary study suggests that the FSHR c.2039A>G GG SNP, which is associated with reduced sensitivity of the FSHR, may have a protective role against obesity, offering further evidence for the possible association among FSH, FSHR polymorphisms, and insulin metabolism.

Toll-Like Receptor Genes and Risk of Latent Tuberculosis Infection in People Infected with HIV-1.

The purpose of this study was to determine the contribution of genetic factors, i.e., the level of expression and polymorphisms of Toll-like receptors (TLR), to the susceptibility of latent tuberculosis infection in a Russian cohort of individuals infected with HIV. The patients (n = 317) with confirmed HIV infection were divided into two groups according to the results of the STANDARD E TB-Feron test: 63 cases with a latent TB infection and 274 controls without LTBI. Total DNA and RNA were isolated from whole-blood samples. SNP genotyping and expression levels of five TLR genes (TLR1, TLR2, TLR4, TLR6, and TLR8) were determined by means of real-time PCR. There were no significant differences in the expression levels of the TLRs between the case and control groups. In addition, we did not observe any significant association between the analyzed SNPs and the susceptibility of Latent tuberculosis infection (LTBI) in patients with HIV. However, patients from an entire cohort with the rs4986790-GG (TLR4) and rs5743708-GG (TLR2) genotypes were characterized by lower CD4 T-cell counts compared to carriers of alternative alleles. Moreover, we found a significant risk of a hazardous drop in the CD4 T-cell count below 350 cells/mm3 associated with the rs4986790-G (TLR4) allele. Latent tuberculosis infection in individuals infected with HIV does not significantly modify the level of TLR gene expression.

Relation of T Cell Profile with Vitamin D Receptor and Vitamin D-Binding Protein Gene Polymorphisms in Atopy.

Atopic diseases, including atopic dermatitis (AD) and allergic asthma (AA), are characterized by complex immune responses involving various T cells subsets and their cytokine profiles. It is assumed that single nucleotide polymorphisms (SNPs) in the Vitamin D receptor (VDR) gene and the Vitamin D-binding protein (GC) gene are related to the action of Vitamin D and, consequently, play a role in regulating the immune response. However, there is not enough data to unequivocally support the hypothesis about the relationship between T cells profile and VDR or GC SNPs. Two hundred sixty-six subjects (aged > 18 years) were involved in the study: 100 patients with mild or moderate AD, 85 patients with mild or moderate AA, and 81 healthy individuals. Blood cell counts were determined by standard methods. Flow cytometric analysis was used to evaluate CD4+ T-helper (Th) cell subtypes: Th2, Th1, Th17, and T regulatory (Treg) cells in peripheral blood. Measurements of cytokines, total immunoglobulin E (IgE), and Vitamin D levels in serum were evaluated by ELISA. Significantly higher levels of Th1, Th2, and Th17 cells, along with lower levels of Tregs, were found in patients with atopic diseases compared to healthy individuals. Additionally, higher serum levels of interleukin (IL) 5, IL-17A, and transforming growth factor-β1 (TGF-β1), as well as lower levels of IL-10, were observed in patients with atopic diseases than in control. The study established associations between VDR SNPs and immune profiles: the AA genotype of rs731236 was associated with increased Th2 and Th17 cells and a higher Th1/Th2 ratio; the GG genotype of rs731236 was linked to decreased serum IL-10 and TGF-β1 levels; and the TT genotype of rs11168293 was associated with increased IL-10 levels. Additionally, the GG genotype of GC gene SNP rs4588 was associated with reduced Th2 and Th17 lymphocytes, while the TT genotype of rs4588 was linked to decreased IL-10 levels. Furthermore, the CC genotype of rs7041 was associated with higher levels of Th2, Th17, IL-10, and IL-35, as well as reduced levels of TGF-β1, while the GG genotype of rs3733359 was associated with reduced IL-10 levels. In conclusion, our study demonstrates that the Vitamin D receptor gene single nucleotide polymorphisms rs731236 and rs11168293, along with polymorphisms in the Vitamin D-binding protein gene (rs4588, rs7041, rs3733359), are significantly associated with variations in T cell profiles in atopy. These variations may play a crucial role in promoting inflammation and provide insight into the genetic factors contributing to the pathogenesis of atopy.