Association of Polymorphisms in Inflammatory Cytokines Encoding Genes With Anti-N-methyl-D-Aspartate Receptor Encephalitis in the Southern Han Chinese

Background: Single nucleotide polymorphisms (SNPs) that occur within genes encoding inflammatory cytokines can result in quantitative or qualitative changes in their expression or functionality, potentially leading to the development of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. This study sought to evaluate the relationship between SNPs in inflammatory cytokines genes and the incidence of anti-NMDAR encephalitis in the Southern Han Chinese.Methods: In total, we enrolled 107 patients with anti-NMDAR encephalitis as well as 202 inpatient controls who had no first-degree relative with autoimmune diseases. Genotyping determination of all 309 patients was conducted for the IL-1β rs16944, IL-4 rs2243250, IL-4 rs2070874, IL-6 rs1800796, IL-10 rs1800872, and IL-17 rs2275913 gene SNPs.Results: We observed statistically significant differences in the frequencies of G allele in IL-1β rs16944 between anti-NMDAR encephalitis and controls (p = 0.017). Also, IL-1β, IL-4, IL-6, IL-10, and IL-17 SNPs were not associated with the disease (p > 0.05).Conclusions: We found that patients with anti-NMDAR encephalitis exhibit a distinct immunological profile, and we found that the decreased frequency of G allele in IL-1β rs16944 showed a protective role for anti-NMDAR encephalitis in the Southern Han Chinese.

Download Full-text

Association Between Polymorphisms of the Complement 3 Gene and Schizophrenia in a Han Chinese Population

Cellular Physiology and Biochemistry ◽

10.1159/000489654 ◽

2018 ◽

Vol 46 (6) ◽

pp. 2480-2486 ◽

Cited By ~ 5

Author(s):

Shangchao Zhang ◽

Na Zhou ◽

Rui Liu ◽

Wenwang Rao ◽

Mingjia Yang ◽

...

Keyword(s):

Chinese Population ◽

Significant Risk ◽

Protective Role ◽

Han Chinese ◽

Genotype Distribution ◽

Distribution Analysis ◽

Nucleotide Polymorphisms ◽

Han Chinese Population ◽

Complement 3 ◽

Risk Effect

Background/Aims: Schizophrenia is a severe psychiatric disorder, and complement 3 (C3) is closely related to schizophrenia. We investigated the association between C3 polymorphisms and schizophrenia in a Northeast Han Chinese population. Methods: A total of 2240 Chinese people, consisting of 1086 patients with schizophrenia and 1154 healthy controls, were recruited for this study. Ten single nucleotide polymorphisms (SNPs; rs11569562, rs344555, rs2241393, rs2241392, rs11569514, rs445750, rs451760, rs11672613, rs2230205, and rs2250656) in C3 were selected and genotyped. Results: Genotype distribution analysis indicated that rs11569514 was significantly associated with schizophrenia. In the dominant model (AA vs. GG+GA genotypes), we found a significant protective effect for rs344555 against schizophrenia (odds ratio [OR]: 0.72, 95% confidence interval [CI]: 0.53–0.99, P = 0.04). In the codominant model (TT vs. AA), we found a significant risk effect for rs11569514 on schizophrenia (OR: 4.39, 95% CI: 2.06–9.37, P < 0.001). Haplotypes, including TG (rs11569562 and rs344555), TGG (rs11569562-rs344555-rs2241393), AG (rs344555-rs2241393), CGGGT (rs11569562-rs344555-rs2241393-rs2241392-rs11569514), and ACGTG (rs11569514-rs445750-rs451760-rs11672613-rs2230205), showed either a risk or protective role for schizophrenia. Conclusions: SNP rs11569514 in C3 and haplotypes of C3 variants were associated with schizophrenia in a Han Chinese population.

Download Full-text

Variation of genes encoding KAT1, AADAT and IDO1 as a potential risk of depression development

European Psychiatry ◽

10.1016/j.eurpsy.2018.05.001 ◽

2018 ◽

Vol 52 ◽

pp. 95-103 ◽

Cited By ~ 4

Author(s):

Paulina Wigner ◽

Piotr Czarny ◽

Ewelina Synowiec ◽

Michał Bijak ◽

Monika Talarowska ◽

...

Keyword(s):

Selective Serotonin Reuptake Inhibitors ◽

Nucleotide Polymorphisms ◽

Male Population ◽

Gene Encoding ◽

Single Nucleotide ◽

Genes Encoding ◽

Numerous Data ◽

Tryptophan Catabolites ◽

Hydroxyanthranilic Acid ◽

The Relationship

AbstractBackground:Numerous data suggests that the disorders of tryptophan catabolites (TRYCATs) pathway, including a decreased level of tryptophan or evaluated concentration of harmful TRYCATs −kynurenine, quinolinic acid, 3-hydroxyanthranilic acid, 3-hydroxytryptophan − may cause the occurrence of DD symptoms. In this work, we assessed the relationship between single-nucleotide polymorphisms (SNPs) of KAT1, KAT2 and IDO1 gene encoding, and the risk of depression development. Our study was performed on the DNA isolated from peripheral blood of 281 depressed patients and 236 controls. We genotyped, by using TaqMan probes, four polymorphisms: c.*456G > A of KAT1 (rs10988134), c.975-7T > C of AADAT (rs1480544), c.-1849C > A (rs3824259) and c.-1493G > C(rs10089084)of IDO1. We found that only the A/A genotype of c.*456G > A − KAT1 (rs10988134) increased the risk of depression occurrence. Interestingly, when we stratified the study group according to gender, this relationship was present only in male population. However, a gene–gene analysis revealed a link between the T/T-C/C genotype of c.975-7T > C − AADAT (rs1480544)or c.-1493G > C − IDO1 (rs10089084) and C/C-C/A genotype of c.975-7T > C − AADAT (rs1480544)and c. −1849C > A − IDO1 (rs3824259) and the disease. Moreover, we found, that the c.975-7T > C − AADAT and c. *456G > A KAT1 (rs10988134) polymorphisms may modulate the effectiveness of selective serotonin reuptake inhibitors therapy. Concluding, our results confirm the hypothesis formulated in our recently published article that the SNPs of genes involved in TRYCATs pathway may modulate the risk of depression. This provides some further evidence that the pathway plays the crucial role in development of the disease.

Download Full-text

Pharmacogenetic pathway analysis for determination of sunitinib-induced toxicity

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.5006 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 5006-5006

Author(s):

N. van Erp ◽

R. H. Mathijssen ◽

A. A. van der Veldt ◽

J. B. Haanen ◽

A. K. Reyners ◽

...

Keyword(s):

Drug Targets ◽

Single Agent ◽

Mucosal Inflammation ◽

Nucleotide Polymorphisms ◽

Genetic Determinants ◽

Metabolizing Enzymes ◽

Genes Encoding ◽

Hand Foot Syndrome ◽

T Haplotype

5006 Background: To identify genetic markers in the pharmacokinetic and pharmacodynamic pathways of sunitinib that predispose for development of toxicities; thrombocytopenia, leukopenia, mucosal inflammation, hand-foot syndrome and ‘any toxicity according to Common Terminology Criteria > grade 2.’ Methods: A multicenter pharmacogenetic association study was performed in 219 patients treated with single agent sunitinib. A total of 31 single nucleotide polymorphisms in 12 candidate genes, together with several non-genetic variants, were analyzed for a possible association with toxicity. In addition, genetic haplotypes were developed and related to toxicity. Results: The risk for leukopenia was increased when the G-allele in CYP1A1 2455A/G (OR = 6.24; p = 0.029) or the T-allele in FLT3 738T/C (OR = 2.8; p = 0.008) were present or CAG in the NR1I3 (5719C/T, 7738A/C, 7837T/G) haplotype (OR = 1.74; p = 0.041) was absent. ‘Any toxicity > grade 2’ prevalence was increased when the T-allele of VEGFR-2 1191C/T (OR = 2.39; p = 0.046) or a copy of TT in the ABCG2 (-15622C/T, 1143C/T) haplotype (OR = 2.63; p = 0.016) were present. The risk for mucosal inflammation was increased in the presence of the G-allele in CYP1A1 2455A/G (OR = 4.03; p = 0.021) and the prevalence of hand-foot syndrome was increased when a copy of TTT in the ABCB1 (3435C/T, 1236C/T, 2677G/T) haplotype (OR = 2.56; p = 0.035) was present. Conclusions: This exploratory study suggests that polymorphisms in specific genes encoding for metabolizing enzymes, efflux transporters and drug targets are associated with sunitinib related toxicities. A better understanding of genetic and non-genetic determinants of sunitinib toxicity should help to optimize drug treatment in individual patients. [Table: see text]

Download Full-text

Polymorphisms in the P2X7 receptor, and differential expression of Toll-like receptor-mediated cytokines and defensins, in a Canadian Indigenous group

Scientific Reports ◽

10.1038/s41598-019-50596-0 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

Catlin Semple ◽

Ka-Yee Grace Choi ◽

Andrea Kroeker ◽

Lizette Denechezhe ◽

Pamela Orr ◽

...

Keyword(s):

First Nations ◽

Inflammatory Cytokines ◽

Mononuclear Cells ◽

Purinergic Receptor ◽

Nucleotide Polymorphisms ◽

Toll Like Receptor ◽

P2x7 Receptors ◽

Genes Encoding ◽

Nfκb Pathway ◽

Pro Inflammatory Cytokines

Abstract Canadian Indigenous peoples (First Nations and Inuit) exhibit a high burden of infectious diseases including tuberculosis influenced by societal factors, and biological determinants. Toll-like receptor (TLR)-mediated innate immune responses are the first line of defence against infections. We examined the production of a panel of 30 cytokines in peripheral blood-derived mononuclear cells (PBMC) isolated from Indigenous and non-Indigenous participants, following stimulation with five different TLR ligands. The levels of TLR-induced pro-inflammatory cytokines such as IL-12/23p40, IL-16, and IFN-γ, and chemokines (MCP-4, MDC and eotaxin) were different between Indigenous compared to non-Indigenous participants. Antimicrobial cationic host defence peptides (CHDP) induced by TLR activation are critical for resolution of infections and modulate the TLR-to-NFκB pathway to alter downstream cytokine responses. Therefore, we examined the expression of human CHDP defensins and cathelicidin in PBMC. mRNA expression of genes encoding for def-A1 and def-B1 were significantly higher following stimulation with TLR ligands in Indigenous compared to non-Indigenous participants. The purinergic receptor P2X7 known to be activated by ATP released following TLR stimulation, is a receptor for CHDP. Therefore, we further examined single nucleotide polymorphisms (SNP) in P2X7. Indigenous participants had a significantly higher percentage of a P2X7 SNP which is associated with reduced function and lower ability to clear infections. These results suggest that a higher frequency of non-functional P2X7 receptors may influence the activity of downstream immune mediators required for resolution of infections such as pro-inflammatory cytokines and CHDP defensins, thus contributing to higher burden of infections in Indigenous population.

Download Full-text

Hsa-miR-196a2 Rs 11614913 C>T polymorphism and CRC susceptibility: A case-control study.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e16066 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e16066-e16066

Author(s):

Li-zhu Chen ◽

Yu Chen ◽

Wei-feng Tang ◽

Lin Chen ◽

Jin Lin ◽

...

Keyword(s):

Alcohol Use ◽

Smoking Status ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Genetic Studies ◽

Incidence And Mortality ◽

Genes Encoding ◽

Pcr Method ◽

Relationship Of ◽

The Relationship

e16066 Background: The incidence and mortality rate of Colorectal cancer (CRC) is high worldwide. Many genetic studies have suggested that single nucleotide polymorphisms (SNPS) in genes encoding small molecule RNAs were associated with CRC risk, but the results were different in different studies. In our study, we investigated the general demographic characteristics and the relationship of hsa-mir-196a2 rs11614913 C > T polymorphism and CRC susceptibility in Chinese CRC. Methods: Our study included 1,003 CRC patients and 1,303 controls. Restriction fragment length polymorphism (RFLP-PCR) method was used for genotyping and SAS version 9.4 software for statistical analysis. Results: The incidence of smoking status,alcohol use and BMI in the CRC group (25.82%,17.35%,66.80%) were much higher than that in the control subjects (20.34%,10.44%,52.80%) respectively(P < 0.05). After adjusting age and other factors, hsa-mir-196a2 rs11614913 C > T genotypes were not statistically correlated with CRC risk and tumor location.But the TT genotype in the hsa-mir-196a2 rs11614913 C > T polymorphism reduced the risk of CRC in women (OR = 0.64, 95 CI: 0.42-0.97, P = 0.036). Conclusions: Smoking status,alcohol use and BMI may be main risk factors for CRC development in our study population.The polymorphism of hsa-mir-196a2 rs11614913 C > T gene may affect the risk of CRC in women, which requires further investigation in a larger cohort in the future.

Download Full-text

Genotype Analysis of Fruit Color using a Molecular Marker in Watermelon [Citrul luslanatus (Thunb.) Matsum & Nakai]

HortScience ◽

10.21273/hortsci.40.4.1114b ◽

2005 ◽

Vol 40 (4) ◽

pp. 1114B-1114

Author(s):

Haejeen Bang ◽

Sunggil Kim ◽

Daniel I. Leskovar ◽

Stephen King

Keyword(s):

Molecular Marker ◽

Snp Markers ◽

Fruit Color ◽

Nucleotide Polymorphisms ◽

Coding Region ◽

Color Determination ◽

Genes Encoding ◽

Differential Gene ◽

Different Color

Fruit color and carotenoid composition are important traits in watermelon. Watermelon fruit color inheritance has revealed that several genes are involved in color determination. Carotenoids are known to have various functions in plants and animals, such as providing antioxidant activity and other health benefits for humans, and UV protection and pigmentation for plants. Differential gene activity in the carotenoid biosynthetic pathway may result in different color determination of mature fruit. Eight genes encoding enzymes involved in the pathway were isolated and their structures were characterized. While obtaining full-length cDNA of these enzymes, two single-nucleotide polymorphisms were detected in a coding region of lycopene β-cyclase (LCYB). These SNP markers showed cosegregation with red and canary yellow fruit color based on the genotyping of two segregating populations. This will lead to development of a codominant molecular marker for the selection of LCYB allele, which may allow breeders to distinguish between red and canary yellow watermelon fruit colors at the seedling stage.

Download Full-text

Case report: anti-N-Methyl-D-Aspartate receptor encephalitis and bilateral temporal calcifications

BMC Neurology ◽

10.1186/s12883-020-01962-3 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Yujie Bu ◽

Tinghua Zhang ◽

Jia Guo

Keyword(s):

Computed Tomography ◽

Celiac Disease ◽

Clinical Work ◽

Young Female ◽

Case Presentation ◽

Cerebral Calcifications ◽

Aspartate Receptor ◽

Nmdar Encephalitis ◽

The Relationship ◽

Head Computed Tomography

Abstract Background In this study, we report a case of a young female who was hospitalized for seizures and diagnosed with anti–N-methyl-D-aspartate receptor (NMDAR) encephalitis. Case presentation The main feature of this patient was bilateral temporal calcifications detected by routine head computed tomography (CT). The co-existence of anti-NMDAR encephalitis and cerebral calcifications has not been reported. We supposed that the patient had an incomplete form of celiac disease (CD), epilepsy and cerebral calcifications syndrome (CEC). The patient's symptoms were alleviated by a series of treatments, and she remained stable during the follow-ups. Conclusions Our findings confirm the rarity co-existing anti-NMDAR encephalitis and cerebral calcifications. In future clinical work, we need to elucidate the relationship between anti-NMDAR encephalitis and cerebral calcifications, and the association between anti-NMDAR encephalitis and other co-existing autoimmune disorders.

Download Full-text

Clinical Relevance of Cerebrospinal Fluid Antibody Titers in Anti-N-Methyl-d-Aspartate Receptor Encephalitis

Brain Sciences ◽

10.3390/brainsci12010004 ◽

2021 ◽

Vol 12 (1) ◽

pp. 4

Author(s):

Meng-Ting Cai ◽

Yang Zheng ◽

Sa Wang ◽

Qi-Lun Lai ◽

Gao-Li Fang ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Psychiatric Symptoms ◽

Autoimmune Encephalitis ◽

Memory Deficits ◽

Clinical Severity ◽

Weak Correlation ◽

Aspartate Receptor ◽

Nmdar Encephalitis ◽

Significant Difference ◽

The Relationship

Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is the most common autoimmune encephalitis. To date, there has been no study on the relationship between antibody (Ab) titers and clinical phenotype. This study aims to clarify the relationship between cerebrospinal fluid Ab titers and clinical manifestations of anti-NMDAR encephalitis at onset. Seventy-six consecutive patients with a definite diagnosis were enrolled. The relationship between Ab titers and different onset symptoms including psychiatric symptoms, seizures, and memory deficits were analyzed. We further investigated the correlation between Ab titers and clinical severity as assessed by the modified Rankin scale (mRS) and the clinical assessment scale for autoimmune encephalitis (CASE), respectively. The Ab titers had a median value of 1:10 (range 1:1–1:100). There was no significant difference in titers among various clinical factors including gender and combination of tumor and other diseases (each p > 0.05). Patients presenting with psychiatric symptoms at onset had higher titers than those with seizures (p = 0.008) and memory deficits (p = 0.003). The mRS scores revealed a significant but weak correlation with Ab titers (r = 0.243, p = 0.034), while CASE scores did not correlate with the titers (p = 0.125). Our findings indicated that the Ab titers were associated with the type of onset symptoms, with a higher level of patients with psychiatric symptoms. Regarding the clinical severity, the titers showed a weak correlation with the mRS, but no correlation with the CASE.

Download Full-text

Association of single nucleotide polymorphisms in the somatotropin gene with indicators of meat productivity in meat-wool sheep

Veterinaria i kormlenie ◽

10.30917/att-vk-1814-9588-2021-2-12 ◽

2021 ◽

Author(s):

L.N. Skorykh ◽

I.O. Fominova ◽

D.V. Kovalenko ◽

S.S. Bobryshov

Keyword(s):

Gene Polymorphism ◽

Marker Gene ◽

Practical Importance ◽

Growth Hormone Gene ◽

Nucleotide Polymorphisms ◽

Productivity Indicators ◽

Meat Productivity ◽

Relationship Of ◽

The Relationship

Modern methods, which are based on the use of DNA technology, allow scientists to improve the accuracy and efficiency of traditional breeding by using molecular markers. One of the ways to identify markers is DNA assessment in the candidate gene, which is the basis of the trait and contributes to the manifestation of the phenotypic characteristics of the organism. Currently, there is growing interest in the genetic improvement of economically important traits in sheep [Fatima Abd Al-Muhsen et al., 2019]. The study of the relationship between gene polymorphism and productivity indicators has high practical importance, which lies in solving many applied problems of breeding. One of these tasks is to determine genetic markers which affect the meat productivity of sheep [Serdyuk G.N., Prituzhalova A.O., 2019; Pogodaev V.A., Kononova L.V., et al., 2019; Lushnikov V.P., Fetisova T.O., Selionova M.I. et al., 2020]. Growth hormone gene GH, which controls and regulates the growth and development of animals, can be considered as a promising marker gene for evaluating meat productivity. The study focuses on the research of the somatotropin gene polymorphism and the analysis of its associations with the indicators of meat productivity of meat-wool sheep of the genotype 1/2 Poll Dorset x 1/2 North Caucasian meat-wool (1/2 PD х 1/2 SC), which are bred in the Stavropol Territory. Polymorphism of somatotropin gene loci was carried out by polymerase chain reaction (PCR) followed by the determination of the restriction fragments lengths – RFLP. The results of PCR showed that the polymorphism of somatotropin gene is represented by two alleles A and B. When studying the polymorphism of GH gene in the experimental animals, genotypes AA, BB and AB were found with different frequency of occurrence. It was found that the heterozygous AB genotype (42.8%) was the most common in meat-wool sheep, while the homozygous AA and BB variants were basically equal and amounted to 29.7 and 27.5%. Further research made it possible to analyze the relationship of the allelic variants of the somatotropin gene with the slaughter parameters of meat-wool sheep. Based on the results, we found that the presence of heterozygous AB and homozygous BB genotypes has a positive effect on the indicators of sheep meat productivity.

Download Full-text