Significant Difference In Genotype Distribution Research Articles

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.

Genetic variants in the retinoid X receptor gene contribute to osteoarthritis susceptibility

Osteoarthritis (OA) is a progressive disease of the joints that causes a gradual loss of function, resulting in limited mobility. Chronic inflammation is the main molecular process that triggers and propagates this disease. The retinoid X receptor (RXR), a member of the nuclear receptor family, is involved in modulating inflammatory pathways by influencing key pro-catabolic inflammatory cytokines, chemokines, and enzymes responsible for instigating and sustaining chronic joint inflammation. We evaluated the association between OA risk and genetic variants in the RXR? isoform. Compared to control individuals, a statistically significant difference in genotype distribution was detected for the rs7864987 polymorphism (P=0.008), while a positive inclination toward association was noted for rs3118523 (P=0.077). According to our findings based on the additive model, it appears that RXR? rs7864987 is linked to a higher risk of OA (adjusted odds ratio (OR)=1.846, P=0.012), whereas rs3118523 is associated with decreased risk of OA (adjusted OR=0.569, P=0.030). These results suggest that RXR? could be a significant inflammation-related gene involved in the complex network underlying the immunopathology of osteoarthritis. RXR? polymorphisms could potentially drive individualized retinoid therapy for OA based on genetic profile.

Single nucleotide variants in the CCL2, OAS1 and DPP9 genes and their association with the severity of COVID-19 in an Ecuadorian population.

COVID-19 has a broad clinical spectrum, ranging from asymptomatic-mild form to severe phenotype. The severity of COVID-19 is a complex trait influenced by various genetic and environmental factors. Ethnic differences have been observed in relation to COVID-19 severity during the pandemic. It is currently unknown whether genetic variations may contribute to the increased risk of severity observed in Latin-American individuals The aim of this study is to investigate the potential correlation between gene variants at CCL2, OAS1, and DPP9 genes and the severity of COVID-19 in a population from Quito, Ecuador. This observational case-control study was conducted at the Carrera de Biologia from the Universidad Central del Ecuador and the Hospital Quito Sur of the Instituto Ecuatoriano de Seguridad Social (Quito-SUR-IESS), Quito, Ecuador. Genotyping for gene variants at rs1024611 (A>G), rs10774671 (A>G), and rs10406145 (G>C) of CCL2, OAS1, and DPP9 genes was performed on 100 COVID-19 patients (43 with severe form and 57 asymptomatic-mild) using RFLP-PCR. The genotype distribution of all SNVs throughout the entire sample of 100 individuals showed Hardy Weinberg equilibrium (P=0.53, 0.35, and 0.4 for CCL2, OAS1, and DPP9, respectively). The HWE test did not find any statistically significant difference in genotype distribution between the study and control groups for any of the three SNVs. The multivariable logistic regression analysis showed that individuals with the GG of the CCL2 rs1024611 gene variant had an increased association with the severe COVID-19 phenotype in a recessive model (P = 0.0003, OR = 6.43, 95% CI 2.19-18.89) and for the OAS1 rs10774671 gene variant, the log-additive model showed a significant association with the severe phenotype of COVID-19 (P=0.0084, OR=3.85, 95% CI 1.33-11.12). Analysis of haplotype frequencies revealed that the coexistence of GAG at CCL2, OAS1, and DPP9 variants, respectively, in the same individual increased the presence of the severe COVID-19 phenotype (OR=2.273, 95% CI: 1.271-4.068, P=0.005305). The findings of the current study suggests that the ethnic background affects the allele and genotype frequencies of genes associated with the severity of COVID-19. The experience with COVID-19 has provided an opportunity to identify an ethnicity-based approach to recognize genetically high-risk individuals in different populations for emerging diseases.

Association between the MCP-1 -2518 A > G (rs1024611) polymorphism and susceptibility to type 2 diabetes mellitus and diabetic nephropathy: a meta-analysis

BackgroundStudies evaluating the association between monocyte chemoattractant protein-1 (MCP-1) -2518 A > G (rs1024611) polymorphism and type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) are contradictory. The present study aims to provide a comprehensive assessment and more reliable estimation of the relationship between the MCP-1 rs1024611 polymorphism and T2DM and DN risk.MethodsEligible articles were retrieved from the PubMed, Web of Science, EMBASE, Cochrane, and China National Knowledge Infrastructure databases. The effect summary odds ratios (ORs) and 95% confidence intervals (CIs) were obtained to calculate the summary effect size. Heterogeneity was analyzed by subgroup analysis and meta-regression. Publication bias was tested using funnel plots and Egger’s test.ResultsIn total, sixteen studies were included. Thirteen studies involving 2,363 patients with T2DM and 4,650 healthy controls found no significant association between the MCP-1 rs1024611 polymorphism and T2DM in the overall population. Ethnicity stratification found an association between the GG + GA genotype and decreased T2DM risk in Caucasians (OR = 0.79, 95% CI: 0.66–0.93, P = 0.006; PQ = 0.372). No significant risks were found in the Asian population for any genetic models. Seven studies found an association between the GG + GA genotype and DN risk in the Asian population (OR = 1.37, 95% CI: 1.11–1.71, P = 0.004, PQ = 0.222). No significant risks were found in the Caucasian population with any genetic models. There were no statistically significant differences in genotype distribution between patients with T2DM and DN in Asians or Caucasians. Meta-regression revealed that genotyping method was a major driver of heterogeneity in five genetic models (GG + GA vs. AA: P = 0.032; GG vs. GA + AA: P = 0.028; GG vs. AA: P = 0.035; GG vs. GA: P = 0.041; G vs. A: P = 0.041).ConclusionThe MCP-1 rs1024611 polymorphism is associated with susceptibility to T2DM in Caucasians and DN in Asians. Larger, well-designed cohort studies are needed in the future to verify this association.

Study on the association between adverse drug reactions to opioids and gene polymorphisms: a case-case–control study

ObjectiveAdverse drug reactions (ADRs) caused by opioid drugs show individual differences. Our objective was to explore the association between gene polymorphism and ADRs induced by opioid drugs.MethodsEvidence-based medical data analysis was conducted for genes related to ADRs induced by opioid drugs to select target genes. Sixty patients with cancer pain who had ADRs after taking opioid drugs (morphine, codeine, oxycodone) and 60 patients without ADRs after taking opioid drugs were used as the experimental group and control group, respectively. Then, we used polymerase chain reaction (PCR) or in situ hybridization to detect target genes. By combining with clinical data such as age, sex, dosage and duration of medication, the effect of gene polymorphism on the ADR of patients after taking opioid drugs was statistically analysed.ResultsBased on a database search and evidence-based medical data, we identified CYP2D6*10, CYP3A5*3, ABCB1, and OPRM1 as target genes for detection. The results of statistical analysis showed no significant difference in genotype distribution between the experimental group and the control group (p > 0.05). However, if 32 patients with ADRs after taking oxycodone and 32 controls were selected for comparison, the SPSS22.0 and SNPStats genetic models showed that the ABCB1 (062rs1045642) CT and TT genotypes correlated with the occurrence of ADRs (p < 0.05): the total number of CT + TT genotypes in the experimental group was 29 (90.62%), with 11 (34.37%) CT + TT genotypes types in the control group.ConclusionPolymorphism of ABCB1 (062rs1045642) is related to ADRs caused by oxycodone, and the incidence of ADRs is higher with the allele T. Polymorphism of ABCB1 is expected to become a clinical predictor of ADRs to oxycodone, and attention should be given to the occurrence of serious ADRs in patients with ABCB1 (062rs1045642) CT and TT genotypes.

Association between HOTAIR genetic variants and risk of obsessive-compulsive disorder

HOX transcript antisense intergenic RNA (HOTAIR) is a long non-coding RNA with important roles in regulation of autophagy, neurite growth and morphogenesis. Polymorphisms within this gene have been associated with some neuropsychiatric conditions. In the current case-control study, we investigated associations between obsessive-compulsive disorder (OCD) and four single nucleotide polymorphism within this gene, namely rs12826786, rs4759314, rs1899663 and rs920778. There was significant difference in genotype distribution of rs920778 between OCD patients and normal controls (P value = 0.01). rs920778 was associated with risk of OCD in co-dominant model (TT versus CC) in both un-adjusted and adjusted by sex analyses (OR (95 % CI) = 0.66 (0.49–0.88), P value = 0.005 and OR (95 % CI) = 0.63 (0.44–0.91), P value = 0.014, respectively). This SNP was associated with OCD in dominant model (TT+TC versus CC) only in un-adjusted analysis (OR (95 % CI) = 0.52 (0.31–0.88), P value = 0.015). Finally, this SNP was associated with OCD in over-dominant model (CC+TT versus TC) in both un-adjusted and adjusted by sex analyses (OR (95 % CI) = 2.38 (1.33–4.25), P value = 0.003 and OR (95 % CI) = 2.78 (1.31–5.89), P value = 0.008, respectively). The current study shows possible impact of rs920778 on risk of OCD in Iranian population.

Association between HLA-DRB1 gene polymorphisms and genetic susceptibility of early-onset severe preeclampsia

To explore the correlation between the single nucleotide polymorphisms (SNP) of rs3135388, rs114293611 and rs142804168 of HLA-DRB1 gene and early-onset severe preeclampsia (sPE). Blood samples were collected from 102 early-onset sPE mothers and their neonates (sPE group), as well as 120 normotensive mothers and their neonates (control group). Sanger sequencing was performed to compare the genotype distribution, allele frequencies, and differences in genotype distribution after maternal-infant compatibility between the two groups. Statistically significant differences in genotype distribution at rs114293611 of HLA-DRB1 gene were observed between sPE and control groups in both mothers and neonates (P<0.05). The frequency of the T allele at rs114293611 was higher in the sPE group of neonates than that in the control group (P<0.05), while no significant difference was found between the two groups of mothers (P>0.05). The maternal-infant genotype compatibility analysis showed significant differences in genotype distribution between sPE and control groups (P<0.05). There were no significant differences in genotype distribution and allele frequencies at rs3135388 and rs142804168 of HLA-DRB1 gene between the two groups of mothers and neonates (P>0.05). The SNP at rs114293611 of HLA-DRB1 gene may be associated with the development of early-onset sPE in mothers. Maternal-infant genotype compatibility abnormality at rs114293611 of HLA-DRB1 gene may be a predisposition factor for the development of sPE.

Genetic Polymorphisms of very Important Pharmacogene Variants in the Chinese Lisu Population

Aim: Interindividual and interethnic differences in drug efficacy drive the development and progress of pharmacogenomics and precision medicine. This study was performed to enrich the pharmacogenomic information for the Lisu population from China. Methods: 54 very important pharmacogene variants were selected from PharmGKB and genotyped in 199 Lisu individuals. The genotype distribution data of 26 populations were downloaded from the 1000 Genomes Project and analyzed with the χ2 test. Results: Among the 26 populations in the 1000 Genomes Project, African Caribbeans in Barbados; Esan in Nigeria; Gambian in Western Divisions, The Gambia; Luhya in Webuye, Kenya; Yoruba in Ibadan; Finnish in Finland; Toscani in Italy and Sri Lankan Tamil in the UK were the top eight nationalities with the most significant differences in genotype distribution from the Lisu population. The loci of CYP3A5 rs776746, KCNH2 rs1805123, ACE rs4291, SLC19A1 rs1051298 and CYP2D6 rs1065852 were significantly different in the Lisu. Conclusion: The results showed that there were substantial differences in SNPs of very important pharmacogene variants, which can provide a theoretical basis for individualized drug use for the Lisu.

5588568 ASSOCIATION OF MANNOSE-BINDING LECTIN SERUM LEVEL AND PROMOTER GENE VARIANTS RS7096206 AND RS10031251 WITH FREQUENCY OF VASO-OCCLUSIVE EVENTS IN SICKLE CELL DISEASE PATIENTS; AN EGYPTIAN CROSS-SECTIONAL STUDY

Background: Sickle cell disease (SCD) is a genetic blood disorder involving hemoglobin alterations, in addition to endothelial adhesion, thrombosis and inflammation. Low serum Mannose-binding lectin (MBL) levels can enhance SCD-related blood vessel inflammation as well as reduction of phagocytic activity, leading to sickled erythrocyte accumulation on vessel walls and impaired ability to combat infections. This may contribute to the vaso-occlusive (VOC) episodes. Aim: This work aimed to investigate serum MBL level and MBL promoter gene variants distribution among a cohort of Egyptian SCD patients and to describe their association with VOC events frequencies in the studied patients. Methods: This cross-sectional study included 88 steady-state Egyptian SCD patients aged 6-18 years diagnosed and followed up at Pediatric Hematology Unit, Cairo University Children Hospital. Informed consent was obtained willingly from all subjects or their guardians before enrolment in the study. MBL promoter (-221) (rs7096206) X/Y and (-550) (rs10031251) H/L gene variants were studied by Polymerase Chain Reaction- Restriction Fragment Length Polymorphism (PCR-RFLP) technique. Serum MBL level was assayed by ELISA technique with values <500ng/ml considered deficient. Results: The median serum MBL level in SCD patients was 130.9 ng/ml (IQR 71.2-323.9 ng/ml). Patients with serum MBL levels <500ng/ml were significantly older, had longer disease duration and higher rate of VOCs per year, VOCs per lifetime and a higher VOC index (p= 0.039, 0.034, 0.047, 0.040 and 0.008 respectively). Levels <500ng/ml predominated in SS (89.4%) than Sβ groups (70%) (p= 0.023) and in patients with high frequency of VOCs (91.4%) (p=0.008). Serum MBL level correlated negatively with patients’ age, disease duration, hydroxyurea total treatment duration, blood transfusions per lifetime and steady-state HbS level (p= <0.001, <0.001, 0.011, 0.014, 0.031 respectively) but correlated positively with steady-state HbF level (p=0.002). MBL (-221) X/Y both alleles were more associated with (H) allele of MBL (-550) than with L allele (p=0.048), however, with no statistically significant genotype distribution between the studied variants. There was no statistically significant difference in genotype distribution or allele frequencies between MBL (-221) and MBL (-550) in SCD patients regarding serum MBL level, sickle cell type (SS and Sβ), VOCs frequencies or disease severity classes. Conclusion: Serum MBL level rather than studied MBL gene variants is more likely to contribute to the clinical outcomes of SCD; patients with lower MBL levels had a higher rate of VOC per year, per lifetime and a higher VOC index. Meanwhile, the variant genotypes and alleles of the studied MBL promotor gene variants were not associated with MBL deficiency, VOCs, infection events, and disease severity.Further studies to investigate other polymorphisms in MBL gene; MBL exon-1 (codons 52,54 and 57) are recommended. Keywords: MBL, Polymorphism, Sickle cell disease, Vaso-occlusive crises, Egypt

Association of PRMT6, PEX10 and SOX5 genetic variants with idiopathic male infertility: Evidence from North Macedonian population and an updated meta-analysis

PRMT6, PEX10 and SOX5 genetic variants were identified as male infertility-associated loci in a genome-wide association study and further validated in various populations. Still, the results of previous case-control studies varied, which could be due to differences in participants? ethnic backgrounds. The main purpose of the present study was to evaluate the supposed association of these variants with idiopathic male infertility in North Macedonian population. Furthermore, we aimed to conduct the systematic quantitative data synthesis which includes the results of previous studies on the same issue in other European and non-European populations. A total of 137 men from North Macedonia diagnosed with idiopathic infertility and 130 age-matched fertile controls were included in the present case-control study. PCR-RFLP method was used for genotyping. Meta-analysis was performed by OpenMeta-analyst statistical software. Variants rs10842262 in SOX5, rs2477686 in PEX10 and rs12097821 in PRMT6 showed the lack of statistically significant differences in genotype distributions between men diagnosed with idiopathic infertility and the control group. Still, rs10842262 allele G frequency was significantly increased in men with poor sperm concentration (P= 0.024, OR = 2.10, 95%CI 1.08-4.06). Meta-analysis further showed the association of rs10842262 and rs12097821 with the risk of idiopathic male infertility. Our results obtained in North Macedonian population supported the previous reports on the involvement of rs10842262 in the genetic basis of male infertility. The meta-analysis confirmed the association of rs10842262 and rs12097821 with male infertility occurrence. Still, additional studies are needed to support the present findings.

Lack of association between SIX1/SIX6 locus polymorphisms and pseudoexfoliation syndrome in a population from the Republic of Korea

Previous studies have reported the association of the SIX1/SIX6 locus with open-angle glaucoma in various ethnic populations. However, the relevance of the SIX1/SIX6 locus to pseudoexfoliation syndrome (XFS) appears uncertain at present. Thus, we investigated the relationship between polymorphisms in the SIX1/SIX6 locus and XFS in a Korean XFS cohort. A total of 246 participants comprising 167 unrelated Korean patients with XFS and 79 ethnically matched control subjects were recruited. Four polymorphisms of the SIX1/SIX6 locus (rs33912345, rs12436579, rs2179970, and rs10483727) were genotyped using a TaqMan® allelic discrimination assay. Genotypic and allelic associations were analyzed using logistic regression. The minor allele frequency (MAF) of rs33912345 was found to be 0.287 and 0.247 in the XFS cases and controls, respectively, and the MAF of rs12436579 was found to be 0.383 and 0.361 in the XFS cases and control subjects, respectively. The MAF of rs2179970 was found to be 0.090 and 0.095 in the XFS cases and control subjects, respectively, and the MAF of rs10483727 was found to be 0.293 and 0.253 in the XFS cases and control subjects, respectively. Genetic association analysis of 4 SIX1/SIX6 locus single nucleotide polymorphisms (SNPs) revealed no significant difference in genotype distribution between the XFS cases and control subjects in the allelic, dominant, or recessive models (all, P > .05). The current study suggested that SIX1/SIX6 locus polymorphisms (rs33912345, rs12436579, rs2179970, and rs10483727) may not be associated with a genetic susceptibility to XFS in a Korean cohort.

Bebeklerde akut bronşiolit ve surfaktan protein B gen lokusu arasındaki ilişki

Purpose: The aim of this study was to investigate whether there is a relationship between surfactant protein B (SFTPB) C1580T polymorphism and acute bronchiolitis.&#x0D; Materials and Methods: The study analyzed the allele frequency and genotype distribution for the SFTPB C1580T polymorphism using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique in 103 acute bronchiolitis infants and 102 healthy infants.&#x0D; Results: The results showed no association between SFTPB C1580T polymorphism and clinical characteristics of acute bronchiolitis. The distribution of the CT genotype was higher in acute bronchiolitis infants (43%) than in healthy subjects (39%) and distribution of the TT genotype was found lower in acute bronchiolitis infants (38%) than in healthy subjects (41%). No significant differences in genotype distribution and allele frequency for the SFTPB C1580T polymorphism were found between case group and control group&#x0D; Conclusion: SFTPB C1580T gene polymorphism plays no important role in susceptibility to acute bronchiolitis. Further work on the relevance of SFTPB C1580T polymorphism in larger cohorts will require validating our results.

Association of the CASP3 rs4647602 Gene Polymorphism with Periodontitis in South Indians of Tamil Ethnicity.

Objective: Caspase-3 activation is central to apoptosis and is involved in periodontal disease pathogenesis. Thus, CASP3 gene polymorphisms in a population may influence the severity of periodontal disease. In this study we examined the association of the CASP3 rs4647602 alleles and genotypes with periodontitis using cohorts of periodontally diseased and healthy South Indian subjects of Tamil ethnicity. Materials and Methods: Allele specific polymerase chain reaction genotyping were performed to identify CASP3 rs4647602 gene polymorphism in 145 periodontally healthy subjects and 145 periodontitis patients. The associations between gene polymorphism frequencies and the risk of periodontitis were analyzed by the Pearson chi-square test, the Mann Whitney U test, t test, logistic regression and assessed by odds ratio (ORs) and 95% confidence interval (95% CIs). Results: The statistical test results demonstrated a significant difference in genotype distribution between the two groups (p < 0.001) with the variant GG genotype associated with a significantly increased risk for periodontitis (OR = 3.55, 95% CI = 1.89-6.68, p < 0.001). Furthermore, all clinical parameters were highly significantly correlated with the genotypes in periodontitis subjects (p < 0.05). Conclusion: The present study suggests that the rs4647602 GG genotype of CASP3 is associated with the increased periodontitis risk in South Indians of Tamil ethnicity. Clinical Trial Registration Number: (CTRI/2021/03/032412).

Genotyping of ARNTL and CLOCK Circadian Rhythm Gene Polymorphisms in Iranian Patients with Multiple Sclerosis

Background: Multiple sclerosis (MS) is a central nervous system disease accompanied by variable symptoms such as optic neuritis, fatigue, spasticity, neuro-urological dysfunction, paresthesia, and headache. The frequency of MS was reported differently in geographical latitude, which may be in relation to genetic changes in circadian rhythm regulator genes, including aryl hydrocarbon receptor nuclear translocator-like (ARNTL) and circadian locomotor output cycles kaput (CLOCK). Objectives: This study aimed at genotyping rs3789327 in the ARNTL and rs6811520 in the CLOCK genes and their association with MS in the Iranian population. Methods: Totally, 100 patients with relapsing-remitting multiple sclerosis (RRMS) and 100 healthy controls were recruited. DNA extracted from the whole blood of all patients was genotyped by high-resolution melting (HRM) real-time PCR method for the rs3789327 and rs6811520 within the ARNTL and CLOCK genes, respectively, then the HRM results were confirmed by Sanger sequencing method. Results: Our results showed a statistically significant difference in genotype distributions in the CLOCK gene (rs6811520, P = 0.023) in MS and healthy controls, but in the ARNTL gene, there was no significant change in rs3789327 genotypic distribution between MS patients and healthy individuals (P = 0.2). The TC genotype of the rs6811520 was associated with a higher risk for MS [P = 0.006, OR = 4.164, 95% confidence intervals (CI) 1.43 - 12.09]. Conclusions: The present results suggested that genetic variations in the CLOCK gene are a risk factor for MS.

Association of Polymorphisms at the SIX1/SIX6 Locus With Normal Tension Glaucoma in a Korean Population.

We demonstrated that SIX1/SIX6 locus polymorphism (rs10483727 and rs33912345) was significantly associated with a genetic susceptibility to NTG in a Korean population. More studies are needed to investigate whether the SIX1/SIX6 locus is associated with NTG among various ethnic populations. Several previous studies have reported that the relevance of the SIX1/SIX6 locus to open angle glaucoma (OAG) in various ethnic populations. However, definitions of OAG patients were different among those studies. The relevance of the SIX1/SIX6 locus to normal tension glaucoma (NTG) in a Korean population remains uncertain. Therefore, the purpose of this study was to investigate the relationship of the SIX1/SIX6 locus with NTG in a Korean cohort. Patients with NTG and ethnically matched healthy controls were recruited from eye clinics in Korea (210 cases and 117 controls). Four polymorphisms (rs33912345, rs12436579, rs2179970, and rs10483727) of the SIX1/SIX6 locus were genotyped for 327 subjects using a TaqMan single nucleotide polymorphism genotyping assay. The rs33912345 polymorphism was significantly correlated with NTG in the recessive model [odds ratio (OR): 0.265; 95% confidence interval (CI): 0.078-0.898, P =0.033], but not in the allelic and dominant models (both P >0.05). The SNP rs10483727 was significantly associated with NTG in the allelic model (OR: 0.674; 95% CI: 0.464-0.979, P =0.038) and the recessive model (OR: 0.187; 95% CI: 0.058-0.602, P =0.005). Genetic association analysis of SNP rs12436579 and rs2179970 revealed no significant difference in genotype distribution between NTG cases and controls in the allelic, dominant, or recessive models (all P >0.05). The current study found that SIX1-SIX6 locus rs10483727 and rs33912345 polymorphisms were significantly associated with NTG risk in the Korean population.

Quantitative detection of methylated SOCS-1 in schizophrenia and bipolar disorder considering SOCS-1 -1478 CA/del polymorphism and clinical parameters

IntroductionSuppressor of cytokine signaling (SOCS) proteins are the critical negative regulators of immune responses that exert their effects by inhibiting the Jak/Stat signaling pathway.ObjectivesTo investigate quantitative detection of methylated SOCS-1 in schizophrenia and bipolar disorder considering SOCS-1 -1478CA/del polymorphism and clinical parameters.Methods 114 patients with SCZ, 86 patients with BD, and 80 healthy volunteers were included in the case-control study. The patients were consecutively admitted to the outpatient clinic for three months and were evaluated with some scales for clinical parameters. To measure the methylation level of the SOCS-1 gene, bisulfite-converted DNA samples were analyzed using the real-time quantitative methylation-specific PCR method. SOCS-1 -1478CA/del gene polymorphism was evaluated by using the PCR-RFLP.ResultsThe SOCS-1 promoter methylation levels of SCZ (p = .001) and BD (p = .024) were found to be significantly different from the control group. SOCS-1 methylation was significantly different between SCZ groups due to the age of onset (p = .009). Again, SOCS-1 methylation was significantly different between BD groups due to YMRS scale scores (p = .027). While the SOCS-1 genotype distributions of SCZ patients were not found to be statistically different from the control group, a significant difference in genotype distribution between BD patients and healthy controls was found (p = .013).ConclusionsThe methylated SOCS-1 quantity in DNA samples of both SCZ and BD patients was significantly lower than in control samples. Whereas the SOCS-1 -1478CA/del polymorphism was not related to SCZ, it may be associated with the BD.DisclosureNo significant relationships.

Association of SIRT1 single gene nucleotide polymorphisms and serum SIRT1 levels with laryngeal squamous cell carcinoma patient survival rate.

BACKGROUND:SIRT1 is a multifunctional protein, possibly essential in tumorigenesis pathways, which can act both as a tumor promoter and tumor suppressor depending on the oncogenes, specific to particular tumors. Pathogenesis of laryngeal cancer is multifactorial and the association of SIRT1 expression with the clinical characteristics and prognosis of LSCC has not been fully identified.OBJECTIVES: The study aimed to evaluate associations between single gene nucleotide polymorphisms (SNPs) of SIRT1 (rs3818292, rs3758391, and rs7895833), serum SIRT1 levels, and 5-year survival rate in patients with laryngeal squamous cell carcinoma (LSCC).METHODS: The study involved 302 patients with LSCC and 409 healthy control subjects. The genotyping of SNPs was performed using RT-PCR, and serum SIRT1 levels were determined by the ELISA method.RESULTS: Our study found significant differences in genotype distributions of SIRT1 rs3758391 polymorphisms between the study groups. SIRT1 rs3758391 T/T genotype was associated with the increased LSCC development odds (OR 1.960 95% CI 1.028–3.737; 0.041). Carriers of SIRT1 rs3758391 T/T genotype had statistically significantly increased odds of LSCC development into advanced stages under the codominant and recessive genetic models (OR 2.387 95% CI 1.091–5.222; 0.029 and OR 2.287 95% CI 1.070–4.888; 0.033, respectively). There were no statistically significant differences in serum SIRT1 levels between the LSCC and control groups. However, LSCC patients with SIRT1 rs3818292 AG genotype demonstrated a tendency to significantly lower SIRT1 serum levels than controls ( 0.034). No statistically significant associations between SIRT1 (rs3818292, rs3758391, and rs7895833) SNPs and the 5-year survival rate of LSCC patients were found.CONCLUSION: The present study indicated a statistically significant association between the SIRT1 rs3758391 T/T genotype and increased LSCC development odds. LSCC patients with SIRT1 rs3818292 AG genotype showed a tendency to manifest with lower SIRT1 serum levels. No associations between SIRT1 SNPs and the 5-year survival rate of LSCC patients were detected.

Association study of a genetic variant in the long intergenic noncoding RNA (linc01080) with schizophrenia in Han Chinese

BackgroundSchizophrenia is currently considered to be a polygene-related disease with unknown etiology. This research will verify whether the single nucleotide polymorphism (SNP) of the long intergenic noncoding RNA01080 (linc01080) contributes to the susceptibility and phenotypic heterogeneity of schizophrenia, with a view to providing data support for the prevention and individualized treatment of this disease.MethodThe SNP rs7990916 in linc01080 were genotyped in 1139 schizophrenic and 1039 controls in a Southern Chinese Han population by the improved multiplex ligation detection reaction (imLDR) technique. Meanwhile, we assessed and analyzed the association between this SNP and schizophrenics’ clinical symptoms, and the cognitive function.ResultThere was no significant difference in genotype distribution, allele frequency distribution, gender stratification analysis between the two groups. However, the SNP of rs7990916 was significantly associated with the age of onset in patients with schizophrenia (P = 8.22E-07), patients with T allele had earlier onset age compared with CC genotype carriers. In terms of cognitive function, patients with T allele scored lower than CC genotype carriers in the Tower of London score and symbol coding score in the Brief assessment of Cognition (BACS), and the difference was statistically significant (P = 0.014, P = 0.022, respectively).ConclusionOur data show for the first time that linc01080 polymorphism may affect the age of onset and neurocognitive function in patients with schizophrenia.

Association of TNFAIP3 gene polymorphism (rs5029939) with susceptibility and clinical phenotype of systemic lupus erythematosus.

Objectives This study aims to investigate the association of the tumor necrosis factor-alpha inducible protein 3 (TNFAIP3) (rs5029939) gene single nucleotide polymorphism (SNP) with the risk of systemic lupus erythematosus (SLE) and its clinical manifestations in a cohort of SLE patients.Patients and methods This study included a total of 180 participants (18 males, 72 females; mean age: 30.9±10.1 years; range 17 to 59 years) including 90 SLE patients and 90 healthy controls between March 2017 and February 2020. The TNFAIP3 rs5029939 gene polymorphism was identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in all participants.Results There was a significant difference in genotype distribution of the TNFAIP3 rs5029939 SNP between SLE patients and healthy controls, where CG genotype was more common in SLE patients (53.3%) than controls (11.1%) (p=0.001). We found a significant difference in G allele frequency of TNFAIP3 (rs5029939) (37.8% with SLE vs. 5.6% with controls, p=0.001). Genotype CG was significantly associated with lupus nephritis and neuropsychiatric manifestations (p<0.05). Although the response to treatment was numerically higher with the genotype CC, it did not reach statistical significance (p=0.4).Conclusion Our study suggests that TNFAIP3 rs5029939 gene polymorphism is associated with SLE susceptibility and may have an impact on its clinical phenotype. As such association differs among populations of diverse ethnic backgrounds, larger genome-wide association studies are warranted to further elucidate genetic associations.

LTA4H Prevalence and Mortality in Adult Zambians with Tuberculous Meningitis.

We conducted a prospective cohort study to determine the prevalence of leukotriene A4 hydrolase (LTA4H) polymorphisms in Zambian adults with tuberculous meningitis (TBM) and its association with mortality. We completed genotype testing on 101 definite cases of TBM and 119 consecutive non-TBM controls. The distribution of genotypes among TBM patients was as follows: C/C (0.83), C/T (0.14), T/T (0.03). There was no significant difference in genotype distribution between TBM and non-TBM patients. We found no relationship between LTA4H polymorphism and survival. Prospective studies are needed to determine the benefit of adjuvant steroids in TBM based upon population LTA4H genotype. ANN NEUROL 2021;90:994-998.