Differences In Genotype Frequencies Research Articles

Effects of tumor necrosis factor-α rs1800629 and interleukin-10 rs1800872 genetic variants on type 2 diabetes mellitus susceptibility and metabolic parameters among Jordanians.

Diabetes mellitus (DM) is a complex chronic illness with diverse pathogenesis and associations with health complications. Genetic factors significantly contribute to DM development, and tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10) genes play major roles. This study aims to explore the influence of TNF-α rs1800629 and IL-10 rs1800872 genetic variants on T2DM development in Jordanian patients at Jordan University Hospital. One-hundred and 60 diabetic and 159 non-diabetic subjects were genotyped for TNF-α rs1800629. Additionally, 181 diabetic and 191 non-diabetic subjects were genotyped for IL-10 rs1800872 using PCR-RFLP genotyping method. The demographic, lipid, and glycemic parameters of the patients were obtained from the computer records in the hospital. TNF-α rs1800629 and IL-10 rs1800872 genetic variants exhibited significant different frequencies in non-T2DM subjects and T2DM patients. The difference in TNF-α rs1800629 genotype frequency between non-T2DM and T2DM participants was significant under the dominant model, while the IL-10 rs1800872 genotype frequency was significant under the recessive model. A significant association (p<0.05) was observed between TNF-α rs1800629 and total cholesterol levels, and between IL-10 rs1800872 polymorphism and glycosylated hemoglobin (HbA1c) and creatinine levels among T2DM patients. TNF-α rs1800629 and IL-10 rs1800872 are identified as genetic risk factors for T2DM. These variants also correlate with variations in cholesterol, HbA1c, and creatinine levels among T2DM patients. Larger clinical studies are warranted to validate these findings.

The role of rs2236242 at SERPINA12 gene and vaspin level on papillary thyroid carcinoma

Several studies showed that adipokines are associated with types of cancer which are documented to be effective in cancer biology. This study aimed to determine the relationship between vaspin rs2236242 polymorphism and the vaspin level with papillary thyroid carcinoma (PTC), and multinodular goiter (MNG). In this cross-sectional study, we recruited 170 candidates. Ninety patients with newly diagnosed (PTC 60 patients and MNG 30 patients), and 80 participants as a control group referred to Shariati Hospital, Tehran, Iran, were enrolled in the study. The vaspin hormone measurements were conducted utilizing the Elisa Kit. Using Tetra amplification resistant-mutation system polymerase chain reaction (T-ARMS-PCR), the genotype of single nucleotide polymorphism (SNP) rs2236242 was determined. The statistical analysis was performed using SPSS software version 20. Our findings showed significant age and genotype frequency differences in three groups (p-value < 0.05). There was no significant difference in vaspin levels between PTC, and control groups. The level of vaspin in MNG compared to the control group had significantly different, but there were no differences after adjustment for age. Results showed the genotypes of vaspin rs2236242 polymorphism are not associated with the level of vaspin. The genotypes and allele frequencies of vaspin rs2236242 in the PTC and MNG groups were significant compared to the control group. We have found vaspin rs2236242 gene polymorphism as a potential marker of papillary thyroid cancer. The A allele of the vaspin SNP rs2236242 plays a protective role against PTC and MNG. SNP at rs2236242 was not significantly associated with vaspin levels.

MMP-1, MMP-8, and MMP-13 Gene Polymorphisms and Haplotype Is a Risk Factor for Dupuytren Contracture: A Case-Control Study.

There is an increased tissue expression of matrix metalloproteinases (MMPs) on Dupuytren contracture (DC). Genetic polymorphisms (single nucleotide polymorphism [SNPs]) in genes of these enzymes may individually influence these transcriptions. Haplotype analysis, which is the observation of a group of alleles, could be more useful to identify the association between SNPs and DC. The purpose of this study was to evaluate the influence of MMP-1 g.-1607 G>GG (rs1799750), MMP-8 g.-799 C>T (rs11225395), and MMP-13 g.-77 A>G (rs2252070) SNPs individually and in haplotype on DC. A total of 60 patients with a clinical diagnosis of DC were evaluated and matched, according to age and gender, with the control group of 100 patients without this clinical diagnosis. Genomic DNA was extracted from saliva samples, and genotypes were obtained by polymerase chain reaction-restriction fragment length polymorphism. Statistical analysis of the results included Mann-Whitney U test, Chi-squared test, and PHASE and R software, with a significance level of 5%. The 3 SNPs studied showed significant differences in allele and genotype frequencies between the groups: 2G in MMP-1 (P = .018; odds ratio [OR] 1.80 (95% confidence interval [CI], 1.13-2.88)), T in MMP-8 (P = .015; OR 0.53 (95% CI, 0.33-0.88)), and A in MMP-13 (rs2252070) SNPs (P = .040, OR 0.54 (95% CI, 0.33-0.90)) are risk alleles. The global haplotype analysis indicated a significant difference between both groups. In conclusion, MMP-1 g.-1607 G>GG (rs1799750), MMP-8 g.-799 C>T (rs11225395), and MMP-13 g.-77 A>G (rs2252070) SNPs, individually and in haplotype, are a risk factor for DC, indicating that these SNPs may be a potential diagnostic and prognostic factor for DC.

Gene Variants of the OAS/RNase L Pathway and Their Association with Severity of Symptoms and Outcome of SARS-CoV-2 Infection.

The interferon pathway plays a critical role in triggering the immune response to SARS-CoV-2, and these gene variants may be involved in the severity of COVID-19. This study aimed to analyze the frequency of three gene variants of OAS and RNASEL with the occurrence of COVID-19 symptoms and disease outcome. This cross-sectional study included 104 patients with SARS-CoV-2 infection, of which 34 were asymptomatic COVID-19, and 70 were symptomatic cases. The variants rs486907 (RNASEL), rs10774671 (OAS1), rs1293767 (OAS2), and rs2285932 (OAS3) were screened and discriminated using a predesigned 5'-nuclease assay with TaqMan probes. Patients with the allele C of the OAS2 gene rs1293767 (OR = 0.36, 95% CI: 0.15-0.83, p = 0.014) and allele T of the OAS3 gene rs2285932 (OR = 0.39, 95% CI: 0.2-0.023, p = 0.023) have lower susceptibility to developing symptomatic COVID-19. The genotype frequencies (G/G, G/C, and C/C) of rs1293767 for that comparison were 64.7%, 29.4%, and 5.9% in the asymptomatic group and 95.2%, 4.8%, and 0% in severe disease (p < 0.05). Our data indicate that individuals carrying the C allele of the OAS2 gene rs1293767 and the T allele of the OAS3 gene rs2285932 are less likely to develop symptomatic COVID-19, suggesting these genetic variations may confer a protective effect among the Mexican study population. Furthermore, the observed differences in genotype frequencies between asymptomatic individuals and those with severe disease emphasize the potential of these variants as markers for disease severity. These insights enhance our understanding of the genetic factors that may influence the course of COVID-19 and underscore the potential for genetic screening in identifying individuals at increased risk for severe disease outcomes.

The Relationship Between CYP46A1 Polymorphism and Suicide Risk: A Preliminary Investigation.

Suicide is a global public health issue, with a particularly high incidence in individuals suffering from Major Depressive Disorder (MDD). The role of cholesterol in suicide risk remains controversial, prompting investigations into genetic markers that may be implicated. This study examines the association between CYP46A1 polymorphisms, specifically SNPs rs754203 and rs4900442, and suicide risk in a Mexican MDD patient cohort. Our study involved 188 unrelated suicide death victims, 126 MDD patients, and 144 non-suicidal controls. Genotypic and allelic frequencies were assessed using the Real Time-polymerase chain reaction method, and associations with suicide risk were evaluated using chi-square tests. The study revealed significant differences in allelic and genotypic frequencies in rs754203 SNP between suicide death and controls. The CYP46A1 rs754203 genotype G/G was significantly linked with suicide, and the G allele was associated with a higher risk of suicide (OR = 1.370, 95% CI = 1.002-1.873). However, we did not observe any significant differences in genotype distribution or allele frequencies of CYP46A1 rs4900442. Our study suggests that carriers of the CYP46A1 rs754203 G allele (A/G + G/G) may play a role in suicidal behavior, especially in males. Our findings support that the CYP46A1 gene may be involved in susceptibility to suicide, which has not been investigated previously. These results underscore the importance of further research in different populations to elucidate the genetic underpinnings of the role of CYP46A1 in suicide risk and to develop targeted interventions for at-risk populations.

Association study of the Taq1D rs1800498 polymorphism of the DRD2 gene with personality traits in a group of athletes

Introduction: This study investigates an association between the human dopamine receptor 2 gene DRD2 Taq1D rs1800498 polymorphism and personality traits among athletes, exploring the genetic underpinnings of sports performance and psychological characteristics. It aims to understand how genetic factors related to dopamine reception influence athletic predispositions and behaviors. Materials and Methods: An association study was conducted with 391 male participants, comparing 159 sports subjects with 232 non-trained controls. Personality traits were assessed using the NEO Five-Factor Inventory, while the DRD2 Taq1D rs1800498 polymorphism was genotyped through real-time PCR. Results: Significant differences in the DRD2 Taq1D rs1800498 genotype and allele frequencies were found between athletes and controls, with athletes displaying higher scores in extraversion and conscientiousness on the NEO-FFI scales. These findings suggest a genetic influence on certain personality traits relevant to sports performance. Conclusions: The study supports the notion that genetic factors, specifically the DRD2 Taq1D rs1800498 polymorphism, are associated with personality traits that may influence athletic performance. This insight contributes to the field of psychogenetics in sports, offering a deeper understanding of how genetics and personality interact to shape athletic capabilities.

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.&#x0D;

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&amp;gt;T), IDH2 (rs11540478G&amp;gt;A), EGFR (rs231677G&amp;gt;A), and EGFR (rs1468727C&amp;gt;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&amp;gt;T, and EGFR rs1468727C&amp;gt;T SNPs. Univariable Cox model showed that the G/G genotype of rs231677G&amp;gt;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&amp;gt;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&amp;lt;0.001), DFS (HR: 0.34, 95% CI: 0.23-0.50, p-value&amp;lt;0.001) , and PFS (HR: 0.43, 95% CI: 0.30-0.62, p-value&amp;lt;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.

Association of polymorphism (RS1800896) of IL-10 gene and IL-10 gene expression in ovarian cancer patients from Georgia

Background/Aim: Ovarian cancer is one of the most important causes of tumour-associated mortality and morbidity in women. Some genetic alterations, determining predisposition to ovarian cancer have already been identified, but these are mostly syndrome-associated cases, most ovarian tumours are still regarded as sporadic. The aim of this research was to identify new predisposing factors that might increase ovarian cancer risk. Genetic variants of IL-10 gene in patients with ovarian cancer was analysed. Methods: Forty-eight patients with ovarian cancer along with 48 agematched controls were included in the study. Single nucleotide polymorphism (SNP) genotyping and gene expression assays for IL-10 were performed using TaqMan assay (Thermo Scientific, USA). The selected SNP was rs1800896 upstream of IL-10 gene (IL-10-1082). All statistical analyses were performed by GraphPad Prism 9.3.1 for Mac. Results: The genotype distributions of IL-10 gene polymorphisms among cancer and control groups were all according to the expected Hardy-Weinberg equilibrium. There was no statistically significant difference in frequency of genotypes and alleles between the two study groups (p &gt; 0.05). In another analysis, the samples were grouped according to the polymorphic variant IL-10 (-1082) A/G. Subjects having the homozygous variant (A/A) had lower IL-10 mRNA levels than those with the homozygous wild (G/G) genotype in both, ovarian cancer patients and controls, p &lt; 0.05. mRNA levels on IL-10 were different among cases and controls (p &lt; 0.05). Patients with ovarian cancer had higher level of mRNA for IL-10. Conclusions: These results support the theory that IL-10 gene expression levels differ in patients with and without ovarian cancer. Polymorphic variant IL-10 (-1082) A/G couldn't be confirmed to explain this difference in gene expression levels.

Evaluation of gene-gene interaction between the interleukin (IL)-2 and IL-2RA gene polymorphisms in schizophrenia patients in the Turkish Population.

To evaluate the genetic polymorphisms in IL-2 and IL-2RA genes in schizophrenia (SCZ) patients by comparing them with healthy controls. A sample of 127 patients with SCZ and 100 healthy volunteers were included in the case-control study. These individuals were consecutively selected from the Malazgirt State Hospital Psychiatry Outpatient Clinic in Mus, Turkey, over the three months from October 2020 to December 2020. The Structured Clinical Interview for DSM-5 Disorders, Clinician Version (SCID-5-CV) was used to confirm the diagnosis according to the DSM-5 criteria. In addition, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine gene polymorphisms from DNA material. Our findings indicated significant differences in the IL-2 genotype and allele frequencies between SCZ patients and the healthy control group. Specifically, the frequency of the homozygous GG genotype was notably higher in SCZ patients compared to the control group. Conversely, when comparing the IL-2RA genotype and allele frequencies of SCZ patients with the control group, no statistically significant differences were observed between the 2 groups. When compared to individuals with other genotypes, interaction analysis indicated that carriers of the GG/AG (IL-2/IL-2RA) genotype demonstrated a significantly increased risk of SCZ. In light of the analyses, our study indicates that while the IL-2 genotype polymorphism may be considered a risk factor for developing SCZ, the IL-2RA variant was not associated with SCZ among Turkish patients.

Association between TRAF1/C5 Gene Polymorphisms and IgA Vasculitis in Chinese Children

ABSTRACT Objective To investigate the association between loci rs3761847 and rs10818488 of tumor necrosis factor receptor-associated factor 1/complement C5 (TRAF1/C5) gene and the susceptibility to IgAV. Methods 100 blood samples of children with IgAV and 100 blood samples of healthy children were collected from the Third Xiangya Hospital of Central South University from June 2017 to June 2019. The target gene fragment was amplified by polymerase chain reaction (PCR), and the single nucleic acid gene polymorphism of the gene loci was detected by PCR sequencing based typing technique. The association between gene polymorphism of each locus and susceptibility to IgAV was analyzed. Results There were significant differences in both genotype (P < .05) and allele frequencies （P < .05) of rs3761847 of TRAF1/C5 gene between the IgAV group and the control group.Besides, the risks of developing IgAV in children with the TT genotype was 0.495 times and in children with the C allele was 1.627 times of that in children with other genotypes and alleles, respectively (P < .05). For IgAV patients, renal involvement risk in children with CC genotype was 5.859 times of that in children with other genotypes (P < .05). There were no significant differences in genotype (P > .05) and allele frequencies (P > .05) of rs10818488 of TRAF1/C5 gene between the IgAV group and the control group. IgAV patients with TT genotype had a 3.2 times higher risk of renal involvement than those with other genotypes (P < .05). Conclusions There is an association between locus rs3761847 of TRAF1/C5 gene single nucleotide polymorphisms and susceptibility to IgAV. The T allele at locus rs3761847 of TRAF1/C5 gene may be a protective factor for IgAV. The C allele at locus rs3761847 and the T allele at locus rs10818488 of TRAF1/C5 gene may be associated with kidney injury in IgAV.

Association of lncRNA THRIL, HOTAIR genes variations and expression levels with pulmonary tuberculosis

BackgroundLong non-coding RNA (lncRNA) has been implicated in the pathogenesis of pulmonary tuberculosis (PTB). This study aims to investigate the involvement of lncRNA THRIL and HOTAIR gene single nucleotide polymorphisms (SNPs) and their expression levels in PTB susceptibility.MethodsA total of 456 PTB patients and 464 healthy controls participated in our study. we genotyped six SNPs of THRIL and HOTAIR genes using an improved multiple ligase detection reaction (iMLDR). Additionally, real-time reverse-transcriptase polymerase chain reaction was employed to detect the expression levels of THRIL and HOTAIR in peripheral blood mononuclear cells (PBMC) from 78 PTB patients and 84 healthy controls.ResultsNo significant differences in allele and genotype frequencies were observed for THRIL rs1055472, rs11058000, and HOTAIR rs12427129, rs1899663, rs4759314, and rs7958904 polymorphisms between PTB patients and healthy controls (all P > 0.05). Moreover, genotype frequencies of all SNPs did not show any association with PTB susceptibility in the dominant–recessive model. However, the frequencies of rs7958904 CC genotype and C allele in the HOTAIR gene were significantly correlated with leukopenia in PTB patients. Furthermore, the expression levels of the HOTAIR gene were significantly elevated in PTB patients compared to controls.ConclusionsOur study indicates that THRIL and HOTAIR gene SNPs might not contribute to PTB susceptibility, while the level of HOTAIR was increased in PTB patients.

Highlighting allelic variations at the interleukin-19 locus in term of preeclampsia predisposing factors and access to an accurate diagnostic/screening option

BackgroundPreeclampsia is the main cause of preterm parturition and maternal–fetal complications. T helper 1 and T helper 2 cytokines balance is a requirement in normal pregnancy and aberrant in this immunologic balance, play an important role in the pathology of preeclampsia. In previous studies single nucleotide polymorphisms have been associated with the alteration of serum cytokine levels.ObjectiveThis study was aimed to discover association between interleukin-13 (rs20541, and rs56035208) and interleukin-19 (rs1028181 (T/C) and rs2243191(T/C)) polymorphisms with susceptibility to preeclampsia.MethodsIn this case-control study 300 women with and without preeclampsia (n = 150/each) who referred to Zeynabieh Hospital- Shiraz, Iran, from February 2021 to April 2022 were enrolled. For genotyping the interleukin-13 and interleukin-19 polymorphisms, the Allele-specific polymerase chain reaction and direct sequencing method was carried out.ResultsOur statistical results revealed no significant differences in allele and genotype frequencies for interleukin-13 polymorphisms compared to controls. We found that the interleukin‐13 polymorphisms are significantly associated with vulnerability to edema at rs20541 position and maternal drinking at rs56035208 position. But it was interesting to note that the differences of both the allele and genotype frequencies of interleukin-19 polymorphisms and their contribution to the risk of preeclampsia susceptibility were significant.ConclusionsNo risk of preeclampsia was found in all comparisons for interleukin-13 polymorphisms. However, the interleukin-19 polymorphisms were found to confer the risk of preeclampsia in our population.

Loss of Arl6ip5 Gene Function Suppresses Thrombosis in Mice

Background: The genetic contributors to thrombosis have only been partly described. Heterozygous tissue factor pathway inhibitor deficiency ( Tfpi +/-) is a powerful negative genetic modifier of the homozygous FVL ( F5 L/L) phenotype, demonstrating a nearly complete perinatal lethal genetic interaction in F5 L/L Tfpi +/- mice. To identifymutations suppressing lethal thrombosis, we used this F5 L/L Tfpi +/- phenotype for a sensitized genome wide ENU mutagenesis screen. We screened over 12,000 mice and generated a total of 31 thrombosis suppressor variant lines. We were able to identify ENU-induced mutations in 10 of these lines, each potentially representing an independent pathway for reducing thrombosis severity. One of the mutations that suppressed thrombosis in F5 L/L Tfpi +/- mice was a dominant loss of function mutation (i.e. mutation in a single allele) in the ADP Ribosylation Factor Like GTPase 6 Interacting Protein-5 ( Arl6ip5) gene. Interestingly, no direct role(s) of Arl6ip5 gene or protein in hemostasis have been reported. Therefore, the aim of our studies was to investigate the hypothesis that Arl6ip5 deficiency suppresses thrombosis by reducing blood coagulation and platelet reactivity in mice. Methods: We previously generated a mouse model of Arl6ip5 ( Arl6ip5 -) by genome editing, creating a 151 base pair deletion removing an exon 1 splice site. After backcrossing mice carrying the Arl6ip5 - allele to the wildtype C57BL/6J (B6) background, we performed Arl6ip5 +/-intercrosses to determine a potential difference in genotype frequency at weaning. To investigate whether the Arl6ip5 - allele was able to produce a stable mRNA transcript we performed RT-qPCR on whole liver, lung, heart, kidney, and brain samples derived from Arl6ip5 +/+ Arl6ip5 +/- and Arl6ip5 -/- mice. Furthermore, complete blood cell counts were analyzed using the Advia 2120 (N ≥ 10 for each group), and to investigate potential blood coagulation defects, Prothrombin Time (PT) (N ≥ 5 for each group) and activated Partial Thromboplastin Time (aPTT) (N ≥ 8 for each group) assays were performed on plasma from Arl6ip5 +/+ Arl6ip5 +/- and Arl6ip5 -/- mice with the operator blinded to the genotype. Similarly, we performed platelet function analyses on whole blood from Arl6ip5 +/+ Arl6ip5 +/- and Arl6ip5 -/- mice using the Roche Multiplate, with ADP and collagen as agonists (N ≥ 6 for each group). Results: Arl6ip5 +/- x Arl6ip5 +/- crosses resulted in normal Mendelian proportions of progeny observed at weaning (N &amp;gt; 400). No Arl6ip5transcripts were present in any of the Arl6ip5 -/- tissue samples analyzed, whereas heterozygous mice had the expected 50% Arl6ip5 expression levels across all organs as compared to wildtype mice. A significant prolongation was observed in aPTT between Arl6ip5 +/+ and Arl6ip5 -/- animals (p&amp;lt;0.01). Although no differences in platelet counts between genotypes were observed, platelet aggregometry showed significant differences between wildtype Arl6ip5 +/+and Arl6ip5 -/-littermates for platelet aggregation, velocity, and area under the curve in response to ADP agonist (normalized to platelet counts, p&amp;lt;0.01). In addition, collagen-induced aggregometry also yielded significant differences in aggregation velocity. Conclusions: Our results support the hypothesis that Arl6ip5 deficiency contributes to thrombosis suppression by increasing the aPTT and reducing platelet reactivity. Since the PT in Arl6ip5 -/- mice is normal, we speculate that Arl6ip5 -/- is either directly or indirectly affecting one or more of the levels or activity of coagulation factors VIII, IX, XI and XII. Significant differences in ADP- and collagen-induced platelet aggregation between Arl6ip5 +/+wildtype littermates and Arl6ip5 -/- suggests that the lack of Arl6ip5affects an aggregation process common to both pathways. Additional analyses are being performed to refine these mechanisms. Understanding the mechanism by which Arl6ip5 deficiency suppresses thrombosis could provide insights into human thrombosis regulation.

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.

The Methylation in B7-H4 and BTLA Genes are Associated with the Risk of Pulmonary Tuberculosis.

The important roles of B7 homologous body 4 (B7-H4), B and T lymphocyte attenuator (BTLA) in patients with pulmonary tuberculosis (PTB) have been reported. This study aims to evaluate the association among B7-H4 and BTLA genes polymorphism, methylation and PTB susceptibility. Here, we assessed the possible relationship of 10 single nucleotide polymorphisms (SNPs) in B7-H4, BTLA genes with PTB susceptibility in a Chinese population (496 PTB patients and 502 controls) by SNPscan technique. Then, the B7-H4, BTLA genes methylation levels among 98 PTB patients and 97 controls were detected using MethylTarget technique. This study found no significant differences in allele and genotype frequencies of B7-H4 gene rs10754339, rs10801935, rs10923223, rs1937956, rs3738414, BTLA gene rs1982809, rs2971205, rs75368388, rs9288953 variants between PTB patients and controls. Haplotype analysis suggested that the lower frequencies of B7-H4 AATTG haplotype, BTLA GATT haplotype and the higher frequency of BTLA AGTC haplotype were found in PTB patients when compared with controls. We also found that the frequency of BTLA gene rs9288953 C allele was significantly increased in PTB patients with drug resistance. Moreover, the methylation levels of B7-H4 and BTLA genes in PTB patients were greater than that in controls, and rs10754339 variant in B7-H4 gene could affect its methylation level in PTB patients. B7-H4, BTLA genes polymorphism might not affect PTB susceptibility, while the abnormal methylation levels of B7-H4, BTLA genes were associated with the genetic background of PTB.

Genotypic and Allelic Frequencies of GJB2 Variants and Features of Hearing Phenotypes in the Chinese Population of the Dongfeng-Tongji Cohort.

This study aimed to describe the distribution of the genotype and allele frequencies of GJB2 variants in the Chinese population of the Dongfeng Tongji cohort and to analyze the features of the hearing phenotype. We used data from 9910 participants in the Dongfeng Tongji cohort in 2013 and selected nine GJB2 variants. Pure tone audiometry was employed to measure hearing. Differences in genotype and allele frequencies were analyzed via chi-squared test or Fisher's exact test. Of the 9910 participants, 5742 had hearing loss. The genotype frequency of the GJB2 variant c.109G>A was statistically significantly distributed between the normal and impaired hearing groups, but not for the variant c.235delC. A higher frequency of the c.109G>A homozygous genotype was found in the hearing loss group (0.5%) than in the normal hearing group (0.1%). Patients with c.109G>A and c.235delC homozygous mutations exhibited varying degrees of hearing loss, mainly presenting sloping and flat audiogram shapes. A significant difference was found in the genotype frequency of the GJB2 variant c.109G>A between the case and control groups, but not in that of the variant c.235delC. Different degrees of hearing loss and various audiogram shapes were observed in patients with c.109G>A and c.235delC homozygous mutations.

Analysis of Correlation Between Coronary Heart Disease and Genetic Polymorphism Detected by Gold Magnetic Nanoparticles Chromatography.

It aimed to explore the correlation of Glu504Lys locus mutation of aldehyde dehydrogenase-2 (ALDH2) with coronary heart disease (CHD) based on gold magnetic nanoparticles (GMNPs) chromatography and amplification refractory mutation system-PCR (ARMS-PCR). 120 CHD patients admitted to the cardiovascular Department of Wenling First People's Hospital affiliated to Wenzhou Medical University from December 2020 to December 2021 were selected as Case group and 80 non-CHD patients admitted during the same period were selected as Ctrl group. The venous blood and indexes of Total Cholesterol (TC), Triglyceride (TG), Low Density Lipoprotein Cholesterol (LDL-C), High Density Lipoprotein Cholesterol (HDL-C), and Fasting Blood Glucose (FBS) were collected. The ARMS-PCR GMNPs chromatography based on ARMS-PCR and immunochromatography assay was adopted to detect gene polymorphism of ALDH2. Correlation between ALDH2 gene polymorphism and risk factors of CHD was analyzed via logistic regression. In contrast to Ctrl group, the genotypes of GG, GA, and AA in Case group were evidently different (P < 0.05), and the frequency of A allelic gene was obviously increased (P < 0.05). Under the dominant model, frequency of GA + AA genotype in Case group was remarkably higher in contrast to Ctrl group (P < 0.05). Under the recessive model, there was no obvious difference in genotype frequency between two groups. In contrast to Ctrl group, TC, LDL-C, and FBS in Case group were notably increased (P < 0.05), while HDL-C was notably decreased (P < 0.05). The distribution frequency of abnormal LDL-C, HDL-C, and FBS in Case group was notably higher in contrast to Ctrl group (P < 0.05). LDL-C and FBS had no obvious effect on the genotypes and frequency distribution of alleles in CHD patients. However, the frequency distribution of genotypes of GA and AA and A allelic gene in patients with abnormal HDL-C was notably lower in contrast to those with normal HDL-C (P < 0.05). Logistic regression analysis showed that abnormal HDC-C with A allelic gene were independent risk factors for CHD (P = 0.001, OR = 1.934). The gene polymorphism of Glu504Lys locus of ALDH2 was closely related to the pathogenesis of CHD, A allelic gene may be a susceptibility gene for CHD, and patients with abnormal HDC-C and carried A allelic gene had relatively higher incidence of CHD.

THU648 Free Vitamin D And Rs7041 Polymorphism In Vitamin D Binding Protein Gene In Policystic Ovary Syndrome

Abstract Disclosure: P.N. Maidana: None. G.A. Gutierrez: None. M. Rojo: None. G.I. Fernández: None. D. Gonzalez: None. V. Aparicio: None. E. D'Isa: None. S. Demayo: None. L. Maggi: None. B.R. Fabre: None. G.E. Cerrone: None. V. Mesch: None. Introduction: Polycystic ovary syndrome (PCOS) is related with an increased risk of developing metabolic complications, such as vitamin D (VitD) deficiency, which could be in turn associated with insulin resistance and other metabolic risk factors. Most (85-90%) of the circulating VitD is bound to its specific carrier protein (DBP), with a smaller amount (10-15%) bound to albumin and less than 1% exists in a free form, which is the biologically active fraction. So, it should be more useful to determine Free VitD to asses VitD status. Aditionally, the influence of genetic factors on serum VitD levels must be taken into account, such as single nucleotide polymorphisms (SNPs) in the DBP gene, as rs7041 and rs4588. We previously found correlations between VitD and different hormonal and metabolic parameters in PCOS women. In this study our aim is to evaluate if measuring Free VitD in PCOS women gives more information than total VitD, and subsequently, to determine the frequency of SNP rs7041 in the DPB gene. Subjects and methods: 104 women (19-41 years) with PCOS and 64 healthy controls (22-45 years) were initially recruited. In a subgroup of 37 patients and 24 controls, Free VitD was measured by ELISA; in all of them body mass index (BMI) was calculated, waist circumference (WC) was measured as indicator of abdominal obesity, VitD and SHBG were measured by chemiluminescence, triglycerides (TG) and HDL cholesterol (HDL-chol) were determined by enzymatic colorimetric method, total testosterone (To) by electrochemiluminescence and free To (FTo) was calculated from To and SHBG. TG/HDL-chol and Lipid accumulation product (LAP) indexes were calculated, as secondary markers of insulin resistance. The rs7041 variant genotyping was performed in 27 PCOS patients and 27 controls, by PCR real time with TaqMan probes in peripheral blood leucocytes. Statistical analysis was performed by SPSS 22 software. Results: BMI, WC, To, FTo, TG/HDL-chol and LAP were significantly higher in PCOS than controls, while VitD was lower. Free VitD showed no significant differences between patients and controls. VitD levels showed negative correlations with BMI, WC, To, FTo, TG/HDL-chol and LAP. Free VitD only showed a positive correlation with total VitD.No statistical differences in genotype frequencies were observed between patients and controls. Genotype and allelic frequencies analysis could not be performed due to the high presence of heterozygosity in both groups. Conclusions: The fact that we found significant differences between total VitD levels in PCOS and controls but not in Free VitD could be attributed to differences in DBP. The lack of correlations between Free Vit D and the different parameters analyzed suggests that measuring Free VitD in PCOS would not have advantages with respect to total VitD.Variant genotyping analysis must be extended to a larger number of individuals and also other variants could be studied. Presentation: Thursday, June 15, 2023