Significant Differences In Genotype Frequencies Research Articles

Very important pharmacogenetic variants landscape and potential clinical relevance in the Zhuang population from Yunnan province

The gradual evolution of pharmacogenomics has shed light on the genetic basis for inter-individual drug response variations across diverse populations. This study aimed to identify pharmacogenomic variants that differ in Zhuang population compared with other populations and investigate their potential clinical relevance in gene-drug and genotypic-phenotypic associations. A total of 48 variants from 24 genes were genotyped in 200 Zhuang subjects using the Agena MassARRAY platform. The allele frequencies and genotype distribution data of 26 populations were obtained from the 1000 Genomes Project, followed by a comparison and statistical analysis. After Bonferroni correction, significant differences in genotype frequencies were observed of CYP3A5 (rs776746), ACE (rs4291), KCNH2 (rs1805123), and CYP2D6 (rs1065852) between the Zhuang population and the other 26 populations. It was also found that the Chinese Dai in Xishuangbanna, China, Han Chinese in Beijing, China, and Southern Han Chinese, China showed least deviation from the Zhuang population. The Esan in Nigeria, Gambian in Western Division, The Gambia, and Yoruba in Ibadan, Nigeria exhibited the largest differences. This was also proved by structural analysis, Fst analysis and phylogenetic tree. Furthermore, these differential variants may be associated with the pharmacological efficacy and toxicity of Captopril, Amlodipine, Lisinopril, metoclopramide, and alpha-hydroxymetoprolol in the Zhuang population. Our study has filled the gap of pharmacogenomic information in the Zhuang population and has provided a theoretical framework for the secure administration of drugs in the Zhuang population.

Association Analysis of Polymorphisms in Inflammation-Related Genes with Non-Hodgkin Lymphoma Susceptibility

Non-Hodgkin's lymphoma (NHL) is a common hematological malignancy that develops in the lymphatic system. A20, CYLD, IFN-γ, JAK2, PI3KCA, and TP53 are known as inflammation-related genes in autoimmune diseases and cancers. In the end, 126 patients with NHL and 109 healthy individuals with well-characterized clinical profiles were enrolled. Twelve variants in the above genes were determined by the Kompetitive allele-specific PCR (KASP) assay. As a result, among genotyped 12 SNPs, the AG genotype of the rs280500 in the TYK2 gene showed significantly higher frequency in the patient group compared to healthy individuals (P=0.05). In addition, no significant differences in genotype frequencies of the other SNPs were found between the two groups. In conclusion, the rs280500 in the TYK2 gene was the risk variant for NHL susceptibility and additionally contributed to understanding the genetic basis of NHL.

Abstract 5585: Genetic variants of IDH and EGFR as diagnostic and prognostic biomarkers in glioblastoma multiforme: A case-control study in the Jordanian Arab population

Abstract Background: Glioblastoma multiforme (GBM) represents a highly aggressive primary brain tumor with poor prognosis. Mutation in the Isocitrate dehydrogenase (IDH1) gene and epidermal growth factor (EGFR) amplification are key diagnostic markers for GBM. However, the prognostic role of genetic variants of these genes remains unclear. Therefore, we aimed to investigate the association between specific single nucleotide polymorphisms (SNPs) for IDH and EGFR genes, and their impact on the risk and prognosis of GBM patients within the Jordanian Arab population. Methods: We carried out a case-control study involving 63 GBM patients and 226 healthy controls at King Abdullah University Hospital in Jordan. Genomic DNA was extracted from formalin-fixed and paraffin-embedded tissue for GBM patients and blood samples for controls. IDH1 (rs121913500C>T), IDH2 (rs11540478G>A), EGFR (rs231677G>A), and EGFR (rs1468727C>T) SNPs were genotyped and analyzed using the Sequenom iPLEX assay sequencing technique. Overall survival (OS) was analyzed between SNPs using the univariable Cox proportional hazard model. The Cancer Genome Atlas (TCGA-GBM) cohort of 585 patients were analyzed for IDH1, IDH2, and EGFR alterations with OS, disease-free survival (DFS), and progression-free survival (PFS). Single-cell RNA analysis was performed on the following scRNA datasets from the Gene Expression Omnibus (GEO): GSE163108 (n=25,013 cells), and GSE102130 (n=3,321 cells) . Results: Our study revealed a significant difference in genotype frequency between GBM cases and controls for IDH1 rs121913500C>T, and EGFR rs1468727C>T SNPs. Univariable Cox model showed that the G/G genotype of rs231677G>A (EGFR) SNP was associated with better OS in the codominant model (HR: 0.24, 95% CI: 0.08-0.73, p-value=0.012), and rs11540478G>A (IDH2) SNP (HR: 0.02, 95% CI: 0.0-0.29, p-value=0.005) showing significantly better prognosis compared to the A/G genotype. In the TCGA validation cohort, the altered group of IDH1 were significantly associated with better OS (HR: 0.35, 95% CI: 0.24-0.50, p-value<0.001), DFS (HR: 0.34, 95% CI: 0.23-0.50, p-value<0.001) , and PFS (HR: 0.43, 95% CI: 0.30-0.62, p-value<0.001). The scRNA analysis showed predominant expression of IDH1, IDH2, and EGFR by malignant cells, oligodendrocyte precursor cells, and macrophages. Conclusion: Our investigation into the genetic landscape of GBM within the Jordanian population suggest that specific genetic variants, particularly in IDH1 genes and EGFR, may serve as diagnostic and prognostic biomarkers for GBM. Additionally, IDH1 alterations were associated with better prognostic outcomes. Single-cell RNA analysis further illuminates the predominant expression of IDH1, IDH2, and EGFR by malignant cells which can be used as potential avenues for targeted therapies based on genetic profiles. Citation Format: Ayah N. Al-Bzour, Sohaib M. Al-Khatib, Mohammad N. Almajali, Tariq A. Jarrad. Genetic variants of IDH and EGFR as diagnostic and prognostic biomarkers in glioblastoma multiforme: A case-control study in the Jordanian Arab population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5585.

Global Frequency Analyses of Canine Progressive Rod-Cone Degeneration-Progressive Retinal Atrophy and Collie Eye Anomaly Using Commercial Genetic Testing Data.

Hundreds of genetic variants associated with canine traits and disorders have been identified, with commercial tests offered. However, the geographic distributions and changes in allele and genotype frequencies over prolonged, continuous periods of time are lacking. This study utilized a large set of genotypes from dogs tested for the progressive rod-cone degeneration-progressive retinal atrophy (prcd-PRA) G>A missense PRCD variant (n = 86,667) and the collie eye anomaly (CEA)-associated NHEJ1 deletion (n = 33,834) provided by the commercial genetic testing company (Optigen/Wisdom Panel, Mars Petcare Science & Diagnostics). These data were analyzed using the chi-square goodness-of-fit test, time-trend graphical analysis, and regression modeling in order to evaluate how test results changed over time. The results span fifteen years, representing 82 countries and 67 breeds/breed mixes. Both diseases exhibited significant differences in genotype frequencies (p = 2.7 × 10-152 for prcd-PRA and 0.023 for CEA) with opposing graphical trends. Regression modeling showed time progression to significantly affect the odds of a dog being homozygous or heterozygous for either disease, as do variables including breed and breed popularity. This study shows that genetic testing informed breeding decisions to produce fewer affected dogs. However, the presence of dogs homozygous for the disease variant, especially for prcd-PRA, was still observed fourteen years after test availability, potentially due to crosses of unknown carriers. This suggests that genetic testing of dog populations should continue.

A Case-Control Study of the Fokl Polymorphism of the Vitamin D Receptor Gene in Bulgarians With Lumbar Disc Herniation.

The present study investigates whether vitamin D receptor (VDR) gene polymorphisms play a role in intervertebral disc degeneration (IDD), a common cause of low back pain (LBP) and reduced quality of life. Specifically, we examined the FokI VDR polymorphism and its potential association with lumbar disc herniation (LDH) in patients from Bulgaria. Previous studies have suggested a link between mutations in the VDR gene and IDD. We investigated whether a potential connection between VDR polymorphisms and LDH was present by comparing the FokI polymorphism of 60 selected patients (25 to 60) with LDH and 60 healthy volunteers within the same age range. We used polymerase chain reaction to assess the phenotype of the examined subjects and statistical tests to evaluate whether the obtained results were statistically significant. The performed genetic and statistical analyses reviewed significant differences in genotypic frequencies between the patient group and healthy volunteers. The frequency of the F allele is notably higher in patients with LDH (80%) compared to volunteers (52%), while the fallele is more common among patients (86.6%) than volunteers (100%). This study strongly suggests that expression of the F allele of the VDR gene may increase the susceptibility of developing LDH, while having the f allele could potentially have a protective effect. Our results shed light on the underlying complex mechanisms contributing to the development of LDH.

Association Between Apolipoprotein C-3 SstⅠ Polymorphism and Serum Lipids in Patients With Gestational Diabetes Mellitus

To investigate the apolipoprotein C-3 (APOC3) gene Sst Ⅰ polymorphism and its relationship with changes in serum lipids in patients with gestational diabetes mellitus (GDM). A total of 630 pregnant women with GDM and 1027 normal pregnant controls were covered in the study. The genotype and allele frequencies of APOC3 Sst Ⅰ polymorphism were analyzed by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and glucose (Glu) were measured by enzymatic methods. Plasma insulin (INS) was measured by chemiluminescence. Apolipoproteins A 1 (apoA1) and B (apoB) levels were measured by turbidimetric immunoassay. The allele frequencies of S1 and S2 of the APOC3 polymorphism at the SstⅠ locus were 0.704 and 0.296 in the GDM group and 0.721 and 0.279 in the control group, respectively. There was no significant difference in genotype frequency and allele frequency of APOC3 Sst Ⅰ polymorphism between the GDM and the control groups ( P>0.05). In the GDM group, those with S2S2 and S1S2 genotypes had higher plasma HDL-C levels and lower atherogenic index (AI) values than those with S1S1 genotype did, with the differences being statistically significant (all P<0.05). GDM patients were then divided into obesity and non-obesity subgroups. Further subgroup analysis showed that the association of APOC3 genotype with changes in HDL-C levels was observed only in obese GDM patients, while the association of APOC3 genotype with changes in AI values was observed in both obese and nonobese patients. In addition, in obese GDM patients, those with S2S2 genotype had significantly higher plasma TG levels than those with S1S1 and S1S2 genotypes did ( P<0.05 and P<0.01, respectively). In non-obese GDM patients, those with S2S2 genotype had significantly lower apoB/apoA1 ratio than S2S2 carriers did ( P<0.05). No genotype-related effect on lipid and apolipoprotein variations was evident in the normal controls. APOC3 Sst Ⅰ polymorphism in GDM patients is associated with HDL-C and TG levels as well as AI value and apoB/apoA1 ratio. The changes in lipid levels and apolipoprotein ratio showed BMI-dependent features. However, association between polymorphism at the locus and the development of GDM was not observed.

Association of HLA-DRB1/DQB1 Alleles and Genetic Susceptibility to Type 1 Diabetes Mellitus

Objective: This study was conducted to identify the association of HLA-DRB1/DQB1 genes with the susceptibility or resistance to type 1 diabetes mellitus (T1D) among patients between the ages of five and eighteen. Subjects and Methods: The study included 200 Sudanese participants, ages ranging from 5 to 18. One hundred participants were healthy non-diabetic as the control group and 100 with T1D as the case group. The investigation was carried out in Khartoum state. The selection of patients with T1D was from diabetic centers and hospitals. The allele-specific-refractory mutation system-polymerase chain reaction (ARMS-PCR) technique was applied to identify the HLA gene polymorphism. Results: There was a significant difference in genotype frequency across the groups in the current investigation (Kruskal-Wallis, p-value= 0.021). Whereas CG was not substantially different across groups (Chi-square, p-value=0.116), the CC genotype was considerably greater (46.0%) in patients (Chi-square Adjusted p-value0.001). Conclusion: This study found that patients' genotypes and allele frequencies are significantly correlated when compared to those of healthy participants.

The impact of IDH and NAT2 gene polymorphisms in acute myeloid leukemia risk and overall survival in an Arab population: A case-control study.

Acute myeloid leukemia (AML) is a malignancy of the myeloid cells due to the clonal and malignant proliferation of blast cells. The etiology of AML is complex and involves environmental and genetic factors. Such genetic aberrations include FLT3, DNMT3, IDH1, IDH2, NAT2, and WT. In this study, we analyzed the relationship between five, not previously studied in any Arab population, single nucleotide polymorphisms (SNPs) and the risk and overall survival of AML in Jordanian patients. The SNPs are NAT2 (rs1799930 and rs1799931), IDH1 (rs121913500), and IDH2 (rs121913502 and rs1057519736). A total number of 30 AML patients and 225 healthy controls were included in this study. Females comprised 50% (n = 15) and 65.3% (n = 147) of patients and controls, respectively. For AML patients (case group) Genomic DNA was extracted from formalin-fixed paraffin-embedded tissues and from peripheral blood samples for the control subjects group. Genotyping of the genetic polymorphisms was conducted using a sequencing protocol. Our study indicates that NAT2 rs1799930 SNP had a statistically significant difference in genotype frequency between cases and controls (p = 0.023) while IDH mutations did not correlate with the risk and survival of AML in the Jordanian population. These results were also similar in the TCGA-LAML cohorts with the notable exception of the rare NAT2 mutation. A larger cohort study is needed to further investigate our results.

Analysis of GPR126 polymorphisms and their relationship with scoliosis in Marfan syndrome and Marfan-like syndrome in Mexican patients.

Marfan syndrome (MFS) is an inherited connective tissue disorder. As the spinal growth depends on delicate balance of forces, conditions that affect musculoskeletal matrix often lead to spinal deformities. A large cross-sectional study revealed a 63% prevalence of scoliosis among patients with MFS. Multi-ethnic genome-wide association studies and analyses of human genetic mutations showed that variations and mutations of G protein-coupled receptor 126 (GPR126)locus are associated with multiple skeletal defects, including shorter stature and adolescent idiopathic scoliosis. The study included 54 patients with MFS and 196 control patients. The DNA was extracted from peripheral blood using the saline expulsion method and single nucleotide polymorphism (SNP) determination was carried out using TaqMan probes. Allelic discrimination was performed by RT-qPCR. Significant differences in genotype frequencies were found for SNP rs6570507 in relation to MFS and sex (recessive model, OR 2.46, 95% CI 1.03 -5.87; P = 0.03) and rs7755109 (overdominant model, OR 0.39, 95% CI 0.16-0.91; P = 0.03). The most significant association was found in SNP rs7755109, where the frequency of genotype AG was significantly different between MFS patients with scoliosis and those without (OR 5.68, 95% CI 1.09-29.48; P=0.04). This study, for the first time, examined the genetic association of SNP GPR126 with the risk of scoliosis in patients with connective tissue diseases. The study revealed that SNP rs7755109 is associated with the presence of scoliosis in Mexican patients with MFS.

Association of 2 Lysyl Oxidase Gene Single Nucleotide Polymorphisms with Keratoconus: A Nationwide Registration Study.

Keratoconus (KC) is the most common primary ectatic corneal disease, characterized by progressive thinning of the cornea, affecting its shape and structure and leading to visual loss. Lysyl oxidase is an important component of the extracellular matrix and contributes to the homeostasis of corneal stromal extracellular matrix via enzymatic reaction. This nationwide registration study aims to examine the association of KC with 2 known single nucleotide polymorphisms, rs2956540 and rs10519694, in a population of Iranian descent. Case-control. One hundred seventy-eight subjects with KC and 180 clinically healthy subjects participated in the study. Genomic DNA was extracted from peripheral blood samples, and their genotypes were determined using tetra-primer amplification refractory mutation system-polymerase chain reaction. Allele frequency for rs2956540 and rs10519694. Genotype frequency was significantly different between cases and controls for rs2956540 (P value=0.019). The rs2956540 C allele carriers were significantly more frequent among KC cases than healthy controls (P valuechi-square=0.015, P valueFisher exact=0.017). There was a significant difference in genotype frequency between groups for rs10519694 (P value=0.001). T allele carriers were significantly more frequent among KC patients (P valuechi-square=0.002, P valueFisher exact=0.001). Sex stratification revealed no significant differences in genotype frequency between males and females in cases and controls. Fitting the general linear model showed that rs10519694 could be considered a predictor for the development of KC (P value=0.001); however, this was not observed for rs2956540 (P value=0.323). rs2956540 and rs10519694 are associated with KC in a population of Iranian descent. rs10519694 could potentially be used for KC risk prediction.

Adiponectin Gene Polymorphisms and Possible Susceptibility to Metabolic Syndrome among the Sudanese Population: A Case-Control Study.

There is a significant difference in genotypic frequencies of the rs266729, rs2241766, and rs1501299 SNPs and allele frequencies (P < 0.05) between the MetS patients and non-MetS group. MetS patients had a significantly higher serum triglycerides (TG), total cholesterol (TC), and low-density lipoprotein-cholesterol (LDL-C) in the GG genotype of rs2241766 (P < 0.05). Additionally; the TT genotype of rs1501299 had higher SBP, serum TG, TC, and LDL-C (P < 0.05). Multivariate logistic regression analysis showed hypertension, hyperglycemia, BMI, WC, serum TG, ADIPOQ rs2241766 (TG allele), and ADIPOQ rs1501299 (GT allele) had independently predicted the incidence of metabolic syndrome in the Sudanese population. The three investigated SNPs of ADIPOQ were in a moderate linkage disequilibrium (LD) connection according to the LD measures (D' = 0.54, 0.62, and 0.69, respectively). The CTT, CGG, and GTG haplotypes, which consist of three alleles of -11377C > G, +45T > G, and +276G > T, were shown to report 1.788-, 1.622,- and 1.641-fold risks toward MetS susceptibility in Sudanese's population, respectively. Along with clinical and biochemical signs, the ADIPOQ gene's genetic variants (rs266729, rs2241766, and rs1501299), CTT, CGG, and GTG haplotypes are connected to the MetS risk among the Sudanese population.

Influence of the 4G/5G polymorphism of plasminogen activator inhibitor-1 gene in acute unprovoked deep vein thrombosis and residual vein thrombosis

BackgroundPlasminogen activator inhibitor-1 (PAI-1) is an important inhibitor of plasminogen activator, but the role of the PAI-1 4G/5G polymorphism in deep vein thrombosis (DVT) has been contradictory. In this study, we investigated the distribution of the PAI-1 4G/5G genotype in Chinese patients with DVT compared with healthy controls and the association between the PAI-1 4G/5G genotype and the persistence of residual venous occlusion (RVO) after different treatments. MethodsThe PAI-1 4G/5G genotype was determined by fluorescence in situ hybridization in 108 patients with unprovoked DVT and 108 healthy controls. The patients with DVT were treated with catheter-based therapy or anticoagulation only. RVO was assessed by duplex sonography during the follow-up. ResultsThirty-two patients (29.6%) were homozygous for 4G (4G/4G), 62 patients (57.4%) were heterozygous for 4G/5G, and 14 patients (13%) were homozygous for 5G (5G/5G). No significant difference in genotype frequency was found between patients with DVT and controls. A total of 86 patients completed follow-up of ultrasound examination with a mean follow-up of 13.4 ±7.2 months. The results of patients with RVO were significantly different between homozygous 4G carriers (76.9%), heterozygous 4G/5G (58.3%), and homozygous carriers of 5G (33.3%) (P <.05) at the end of follow-up. Catheter-based therapy showed a better result in patients who were noncarriers of 4G (P = .045). ConclusionsThe PAI-1 4G/5G genotype was not a relevant predictor for DVT in Chinese patients, but is a risk factor for persistent RVO after idiopathic DVT.

Selected SNPs of FCN2 Associated with Chronic Tonsillitis in the Polish Adult Population.

Chronic tonsillitis is a problem related to bacterial and viral infections. Ficolins play a key role in the defence against various pathogens. In the present study, we investigated the associations between the selected single nucleotide polymorphisms (SNPs) of the FCN2 gene and chronic tonsillitis in the Polish population. The study included 101 patients with chronic tonsillitis and 101 healthy individuals. The selected SNPs of FCN2 (rs3124953, rs17514136 and rs3124954) were genotyped using TaqMan SNP Genotyping Assays (Applied Biosystem, Foster City, CA, USA). The analysis of rs17514136 and rs3124953 showed no significant differences in genotype frequencies between the chronic tonsillitis patients and controls (p > 0.01). The CT genotype of rs3124954 was significantly more frequent, while the CC genotype was less frequent in chronic tonsillitis patients (p = 0.003 and p = 0.001, respectively). The frequency of the A/G/T haplotype (rs17514136/rs3124953/rs3124954) was significantly more common in chronic tonsillitis patients (p = 0.0011). Moreover, the FCN2 CT genotype of rs3124954 was associated with a higher risk of chronic tonsillitis, while the CC genotype of rs3124954 decreased this risk. Our findings demonstrate that FCN2 rs3124954 may be associated with chronic tonsillitis in the Polish adult population.

The effects of angiotensinogen M235T/T174M and angiotensin type 1 receptor a1166c gene polymorphisms on the development of diabetic nephropathy in type 2 diabetes mellitus patients.

Diabetic nephropathy is one of the major complications of Type 2 diabetes mellitus. In this study, we aimed to investigate the effects of angiotensinogen M235T/T174M and angiotensin type 1 receptor A1166C gene polymorphisms on the development of diabetic nephropathy in patients with type 2 diabetes mellitus. This study included 100 type‑2 diabetes mellitus patients with diabetic nephropathy patients (patient group) and 99 type‑2 diabetes mellitus patients without diabetic nephropathy (control group). Polymerase chain reaction and restriction fragment length polymorphism methods were used to identify polymorphisms in the angiotensinogen M235T/T174M and angiotensin type 1 receptor A1166C genes. There was no significant difference in genotype frequencies of M235T gene polymorphism between patient and control groups (χ2 = 4.01, df = 2, p = 0.13). There was no significant difference in genotype frequencies of T174M gene polymorphism between patient and control groups (X2 = 0.36, df = 2, p = 0.83). There was no significant difference in genotype frequencies of A1166C gene polymorphism between patient and control groups (χ2 = 0.51, df = 2, p = 0.77). The results showed no significant difference in angiotensinogen M235T/T174M and angiotensin type 1 receptor A1166C gene polymorphisms between the patient and control groups. Future studies are needed to validate the results of this study and to explore underlying mechanisms (Tab. 3, Fig. 3, Ref. 35). Text in PDF www.elis.sk Keywords: type 2 diabetes mellitus, diabetic nephropathy, angiotensinogen gene polymorphism, angiotensin type 1 receptor, gene polymorphism.

Association of Single Nucleotide Polymorphisms in the PYGO2 and PRDM9 Genes with Idiopathic Azoospermia in Iranian Infertile Male Patients.

Azoospermia is a risk factor for infertility affecting approximately 1% of the male population. Genetic factors are associated with non-obstructive azoospermia (NOA). Pygo2 and PRDM9 genes are involved in the spermatogenesis process. The present study aimed to assess the association of single nucleotide polymorphism (SNP) in the Pygo2 (rs61758740 and rs61758741) and PRDM9 (rs2973631 and rs1874165) genes with idiopathic azoospermia (IA). A cross-sectional study was conducted from October 2018 to August 2019 at Rooya Infertility Centre (Qom, Iran). A total of 100 infertile patients with NOA and 100 men with normal fertility were enrolled in the study. Tetra-primer amplification refractory mutation system-PCR method was used to detect SNPs rs61758740, rs61758741, and rs2973631. The restriction fragment length polymorphism method was used for SNP rs1874165. In addition, luteinizing, follicle-stimulating, and testosterone hormone levels were measured. The results showed a significant increase in luteinizing and follicle-stimulating hormone levels in the patient group (P<0.001), but a non-significant difference in testosterone levels in both groups. SNP rs61758740 (T>C) was associated with the increased risk of azoospermia (OR: 2.359, 95% Cl: 1.192-4.666, P=0.012). SNP rs2973631 showed a significant difference in genotype frequency between the patient and control groups in the dominant, recessive, and codominant models. However, in the case of SNP rs1874165, the difference was significant in the dominant, codominant, and overdominant models. There is an association between azoospermia and SNPs in Pygo2 and PRDM9 genes in Iranian infertile male patients with IA. SNPs can be considered a risk factor for male infertility. It should be noted that this article was published in preprint form on the website of europepmc (https://europepmc.org/article/ppr/ppr416800).

Association between Interleukin-6 rs1800795 Polymorphism and Serum Interleukin-6 Levels and Full-Term Neonatal Sepsis

Abstract Objective Cytokines are involved in the pathogenesis of sepsis. Association between IL-6 rs1800795 G/C polymorphism and the risks of sepsis is controversial. The aim of this study was to investigate the association of IL-6 rs1800795 G/C gene polymorphism with full-term neonatal sepsis and to determine its effect on the serum IL6 levels in these infants by a prospective study. Methods The study included 200 full-term neonates from January 2019 to December 2020: 100 with sepsis (sepsis group), 47 with culture proven sepsis, and 53 with clinical sepsis, and 100 without infection (control group). The concentrations of IL-6 in serum were determined using enzyme-linked immunosorbent assay (ELISA). The polymorphisms of IL-6 rs1800795 G/C were analyzed to compare the genotypic and allelic frequencies in the groups by using the first-generation sequencing (Sanger sequencing). The association was studied between IL-6 rs1800795 G/C polymorphisms and serum IL-6 levels, and neonatal sepsis. The relationships between IL-6 rs1800795G/C polymorphisms and sepsis and serum IL-6 levels were separately analyzed by logistic regression and analysis of variance. Results There were no significant differences in genotypic frequencies and allelic frequencies of IL-6 rs1800795(G/C) in the groups (p &gt;0.05). There were no relations between IL-6 rs1800795G/C polymorphisms and sepsis and serum IL-6 levels by statistical analysis (p &gt;0.05). Conclusion IL-6rs1800795G/C may not be genetic risk factors for full-term neonates; There was no association between serum IL-6 levels and IL-6 rs1800795G/C polymorphisms.

Impact of SLC23A1 and SLC23A2 Polymorphisms on the Risk for Preeclampsia in a Chinese Han Population.

Solute carrier family 23 member 1 (SVCT1) and solute carrier family 23 member 2 (SVCT2), encoded by SLC23A1 and SLC23A2, may be associated with preeclampsia (PE). The purpose of this study was to investigate the association between polymorphisms of SLC23A1 and SLC23A2 and PE in Chinese Han population. The primers and double-labeled probes were designed according to the SNPs of rs10063949 in SLC23A1, rs6133175 and rs1279683 in SLC23A2. Genomic DNA was extracted from peripheral blood of 2,066 subjects (1,029 with PE and 1,037 without PE), and Taqman real-time PCR was used to detect the three SNPs. We observed a significant difference in genotypic frequency of the SLC23A2 rs6133175 polymorphism (χ2=8.08, p=0.02) between PE patients and controls, while no significant differences were found in the allelic frequencies (χ2=1.45, p=0.23). Then we fractionized these samples into the dominant model of the allele G (GG/AG+AA group) or the recessive model of the A allele (AA/AG+GG group), and observed a significant difference under the recessive model of the A allele (p=0.01, OR=0.71, 95% CI 0.55-0.92). Furthermore, there were no significant differences in the genotypic and allelic frequencies of rs10063949 and rs1279683 between PE patients and controls (for rs10063949, χ2=2.96, p=0.23 by genotype, χ2=2.11, p=0.15 by allele; for rs1279683, χ2=1.52, p=0.47 by genotype, χ2=0.64, p=0.44 by allele). We first found that SLC23A2 rs6133175 may be the certain genetic polymorphisms modulating their effects in the development of PE in a Chinese Han population and the AG or GG genotypes may be a risk factor for PE.

Association of rs2910164 in miR-146a with type 2 diabetes mellitus: A case-control and meta-analysis study.

ObjectiveSeveral studies have shown that miR-146a rs2910164 (C > G) is associated with type 2 diabetes mellitus (T2DM) susceptibility, but the results are still controversial. This study is divided into two parts, and one is to explore the relationship between miR-146a rs2910164 polymorphism and the genetic susceptibility of T2DM in Chinese Han population. Second, a meta-analysis on the basis of a larger sample size was used to determine whether this is a susceptibility gene for T2DM.MethodsA case–control study including 574 T2DM patients and 596 controls was used to evaluate the association of miR-146a rs2910164 polymorphism with the risk of T2DM in Chinese Han People. Then, we systematically searched studies investigating the correlation between miR-146a rs2910164 polymorphism and T2DM susceptibility published before April 2022 from PubMed, Web of Science, Wanfang, and China National Knowledge Infrastructure database, and a meta-analysis including six studies was carried out. The results were expressed by odds ratio (OR) and its 95% confidence interval (95% CI).ResultsIn a case–control study, we found that there were no statistical differences in genotype frequencies between T2DM and control group. Subgroup analysis showed that, compared with the CC genotype, CG + GG genotype was associated with a decreased risk of T2DM in the subgroup of individuals ≥ 65 years old (OR = 0.75; 95% CI: 0.58–0.98; P adjusted = 0.032) and BMI < 18.5 (OR = 0.16; 95% CI: 0.03–0.89; P adjusted = 0.037). In overall meta-analysis, significant heterogeneity was detected. No significant association between miR-146a rs2910164 polymorphism and T2DM was observed in all genetic models under random effects models. Subgroup analysis revealed that there was a significant difference in genotype frequencies between the T2DM and control group in recessive model (CC vs. CG + GG: OR = 1.79; 95% CI: 1.08–2.96; PQ = 0.307, I 2 = 4.0%) and homozygote model (CC vs. GG: OR = 1.79; 95% CI: 1.07–3.00; PQ = 0.216, I 2 = 34.7%) in Caucasians.ConclusionThe results of our study demonstrate that the miR-146a rs2910164 polymorphism might have ethnicity-dependent effects in T2DM and may be related to T2DM susceptibility in Caucasians.

The Effect of Selected Polymorphisms of the ACTN3, ACE, HIF1A and PPARA Genes on the Immediate Supercompensation Training Effect of Elite Slovak Endurance Runners and Football Players.

We aimed to evaluate the effect of selected polymorphisms of the ACTN3, ACE, HIF1A and PPARA genes on the immediate supercompensation training effect of elite Slovak endurance runners and football players compared with a sedentary control group. Adaptation effect levels were evaluated by 10 s continuous vertical jump test parameters measured by Optojump. Genetic polymorphisms were determined by PCR and Sanger sequencing. We found significant differences in the effect of PPARA genotypes in the experimental group. C allele genotypes represented an advantage in immediate supercompensation (p < 0.05). We observed a significant combined effect of multiple genes on immediate supercompensation (p < 0.05): the RR genotype of the ACTN3 gene, the ID genotype of the ACE gene, the Pro/Pro genotype of HIF1A, and the GC and GG genotypes of PPARA genes. In the control group, we found a significant effect (p < 0.05) on immediate supercompensation of the II genotype of the ACE gene and the Pro/Ser genotype of the HIF1A gene. We found significant differences in genotype frequency of ACE (p < 0.01) and PPARA (p < 0.001) genes. We confirmed that individual genetic polymorphisms of ACTN3, ACE, HIF1A and PPARA genes have a different effect on the level of immediate supercompensation of the lower limbs depending on the training adaptation of the probands and the combination of genotypes.

MO616: The Genetic Background Predicts The Kind of Renal Damage and Fibrosis Progression in Diabetic Patients

Abstract BACKGROUND AND AIMS Diabetic Nephropathy (DN) is the major causes of end-stage renal failure. DN diagnosis is based on typical histological features (Kimmelstiel–Wilson lesions, glomerular basal membrane thickening and proliferation of mesangial matrix). Not all diabetic patients with kidney disease develop true DN: kidney impairment can be due to a nondiabetic renal disease (NDRD) in the presence or absence of real DN. Thus, there is the need for noninvasive biomarkers, related to specific pathogenic processes, to discriminate DN and NDRD, and/or to predict DN onset. In the case of DN, there is extensive evidence in literature of genetic contribution to disease susceptibility and lots of efforts aim at the identification of specific loci. The research group demonstrated that a characteristic feature of DN is an increase in Lys63-ubiquitinated proteins at tubular level that leads to epithelial-to-mesenchymal transition (EMT) and finally to the progression of the tubular-interstitial fibrosis and the renal damage in DN patients (Pontrelli P et al. FASEB J 2017). Ube2V1 is the unique E2 enzyme known for producing Lys63-linked ubiquitin chains. Moreover, two miRNAs (miR27b-3p e miR1228-3p), which interact specifically with Ube2V1 transcript, predict the type of renal damage in diabetic patients and are related with kidney fibrosis (Conserva F et al. Sci Rep 2019). The goal of this project was to identify single nucleotide polymorphisms (SNPs) able to predict the different kind of renal damage and the progression of kidney disease in diabetic patients. METHOD We selected by UCSC genome, 10 HapMap SNPs of patients within coding and regulatory sequences both of miR27b-3p and miR1228-3p and Ube2V1 gene in order to evaluate their diagnostic and prognostic potential. The patients enrolled in this study were diabetic patients with a biopsy-proven DN diagnosis (DN), diabetic patients with a biopsy-proven diagnosis of other nephropathy than DN (NDRD), diabetic patients without clinical signs of impaired renal function (T2D), diabetic patients with a biopsy-proven coexistence of both conditions (ND + NDRD), non-diabetic patients with glomerulonephritis (CKD), non-diabetic patients without renal damage (CTRL). The DNA of 201 subjects (patients and controls) was isolated from blood samples, and 10 HapMap SNPs (rs3802456, rs4744422, rs10761364, rs7853195 in the control region of miR27b-3p; rs2306692, rs4759277, rs4759044, rs17547610, rs4759275 in the control region of miR1228-3p; rs761214 in the UBE2v1 gene) for each patient were analyzed using TaqMan real-time PCR. Glomerular and tubulointerstitial fibrosis in kidney biopsies was quantified on Sirius Red staining using the Aperio Imagescope software. RESULTS The analyzed SNPs showed a different genotype frequency among all the patients’ classes. Interestingly, SNPs rs4759275, rs4759277, rs4744422 and rs3802456 showed a statistically significant difference in genotype frequency comparing DN patients with CEU Population (Northern and Western European Ancestry in Utah) (P &amp;lt; 0.04, 0.05, 0.002, 0.001, respectively) and a control cohort enclosing CTRL and T2D (P &amp;lt; 0.02, 0.05, 0.001 and 0.04, respectively). SNPs rs761214, rs10761364 and rs2306692 genotypes frequency was statistically different among DN patients and the control cohort (P &amp;lt; 0.001). The genotype frequencies of the SNPs rs10761364 (P &amp;lt; 0.01) and rs7853195 (P &amp;lt; 0.04) resulted significantly related to tubular fibrosis in DN patients, while the SNPs rs4744422 (P &amp;lt; 0.03) and rs761214 (P &amp;lt; 0.02) to the glomerular one. In order to evaluate the diagnostic power of the identified SNPs, we used a logistic regression model, and we observed that the SNP rs10761364, adjusted for age, sex, eGFR and glycaemic index, discriminate DN from NDRD {P &amp;lt; 0.05; OR = 1.002–1.008; [95% confidence interval (CI)]}. CONCLUSION Our data demonstrated that the allelic forms of the analyzed SNPs are related to the different kind of renal damage in diabetic patients. Their prognostic and diagnostic potential could represent the starting point to create a new noninvasive diagnosis system based on clinical and genotyping data.