Investigation of the Correlation between Graves’ Ophthalmopathy and CTLA4 Gene Polymorphism

Graves’ disease (GD) is an autoimmune inflammatory disease, and Graves’ ophthalmopathy (GO) occurs in 25–50% of patients with GD. Several susceptible genes were identified to be associated with GO in some genetic analysis studies, including the immune regulatory gene CTLA4. We aimed to find out the correlation of CTLA4 gene polymorphism and GO. A total of 42 participants were enrolled in this study, consisting of 22 patients with GO and 20 healthy controls. Chi-square or Fisher’s exact test were used to appraise the association between Graves’ ophthalmopathy and CTLA4 single nucleotide polymorphisms (SNPs). All regions of CTLA4 including promoter, exon and 3’UTR were investigated. There was no nucleotide substitution in exon 2 and exon 3 of CTLA4 region, and the allele frequencies of CTLA4 polymorphisms had no significant difference between patients with GO and controls. However, the genotype frequency of “TT” genotype in rs733618 significantly differed between patients with GO and healthy controls (OR = 0.421, 95%CI: 0.290–0.611, p = 0.043), and the “CC” and “CT” genotype in rs16840252 were nearly significantly differed in genotype frequency (p = 0.052). Haplotype analysis showed that CTLA4 Crs733618Crs16840252 might increase the risk of GO (OR = 2.375, 95%CI: 1.636–3.448, p = 0.043). In conclusion, CTLA4 Crs733618Crs16840252 was found to be a potential marker for GO, and these haplotypes would be ethnicity-specific. Clinical application of CTLA4 Crs733618Crs16840252 in predicting GO in GD patients may be beneficial.

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Association between IFN-γ+874A/T and IFN-γR1 (-611A/G, +189T/G, and +95C/T) Gene Polymorphisms and Chronic Periodontitis in a Sample of Iranian Population

International Journal of Dentistry ◽

10.1155/2015/375359 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 12

Author(s):

Zahra Heidari ◽

Hamidreza Mahmoudzadeh-Sagheb ◽

Mohammad Hashemi ◽

Somayeh Ansarimoghaddam ◽

Bita Moudi ◽

...

Keyword(s):

Gene Polymorphism ◽

Genetic Polymorphisms ◽

Chronic Periodontitis ◽

Gene Polymorphisms ◽

Healthy Controls ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Significant Difference ◽

Pcr Rflp ◽

And Control

Background. Interferon gamma (IFN-γ) is an immune regulatory cytokine that acts through its receptor and plays important role in progression of inflammatory disease such as chronic periodontitis (CP). The purpose of this study was to determine the differences in the distribution of IFN-γ(+874A/T) and IFN-γR1 (-611A/G, +189T/G, and +95C/T) gene polymorphisms among CP and healthy individuals and to investigate relationships between these polymorphisms and susceptibility to CP.Materials and Methods. 310 individuals were enrolled in the study including 210 CP patients and 100 healthy controls. Single nucleotide polymorphisms at IFN-γ(+874A/T) and IFN-γR1 (-611A/G, +189T/G, and +95C/T) were analyzed by ARMS-PCR and PCR-RFLP methods.Results. The significant difference was found in genotype and allele frequency of IFN-γ(+874A/T) gene polymorphism in chronic periodontitis patients and healthy controls. The distribution of genotypes and allele frequencies for IFN-γR1 (-611A/G, +189T/G, and +95C/T) were similar among the groups and no differences in the frequencies of alleles or genotypes of IFN-γR1 genetic polymorphisms variants between case and control groups were detected.Conclusion.The finding of this study showed that IFN-γ+874A/T gene polymorphism may affect susceptibility to CP, whereas IFN-γR1 genetic polymorphisms at -611A/G, +189T/G, and +95C/T were not associated with this disease.

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Significant Associations of lncRNA H19 Genotypes with Susceptibility to Childhood Leukemia in Taiwan

Pharmaceuticals ◽

10.3390/ph14030235 ◽

2021 ◽

Vol 14 (3) ◽

pp. 235

Author(s):

Jen-Sheng Pei ◽

Chao-Chun Chen ◽

Wen-Shin Chang ◽

Yun-Chi Wang ◽

Jaw-Chyun Chen ◽

...

Keyword(s):

Confidence Interval ◽

Childhood Leukemia ◽

Healthy Controls ◽

Nucleotide Polymorphisms ◽

Wild Type ◽

Single Nucleotide ◽

Genotypic Distribution ◽

Heterozygous Variant ◽

Significant Difference ◽

The Difference

The purpose of our study was to investigate whether genetic variations in lncRNA H19 were associated with susceptibility to childhood leukemia. Two hundred and sixty-six childhood leukemia patients and 266 healthy controls were enrolled in Taiwan, and two single nucleotide polymorphisms (SNPs), rs2839698 and rs217727, in H19 were genotyped and analyzed. There was a significant difference in the genotypic distribution of rs2839698 between patients and healthy controls (p = 0.0277). Compared to the wild-type CC genotype, the heterozygous variant CT and homozygous variant TT genotypes were associated with significantly increased risks of childhood leukemia with an adjusted odd ratio (OR) of 1.46 (95% confidence interval (CI), 1.08–2.14, p = 0.0429) and 1.94 (95%CI, 1.15–3.31, p = 0.0169), respectively (pfor tread = 0.0277). The difference in allelic frequencies between childhood leukemia patients and controls was also significant (T versus C, adjusted OR = 1.53, 95%CI, 1.13–1.79, p = 0.0077). There were no significant differences in the genotypic and allelic distributions of rs217727 between cases and controls. Interestingly, the average level of H19 rs2839698 was statistically significantly higher for patients with CT and TT genotypes than from those with the CC genotype (p < 0.0001). Our results indicate that H19 SNP rs2839698, but not rs217727, may serve as a novel susceptibility marker for childhood leukemia.

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Distribution of QPY and RAH haplotypes of granzyme B gene in distinct Brazilian populations

Revista da Sociedade Brasileira de Medicina Tropical ◽

10.1590/s0037-86822012005000001 ◽

2012 ◽

Vol 45 (4) ◽

pp. 496-499

Author(s):

Fernanda Bernadelli Garcia ◽

Simone Kashima ◽

Evandra Strazza Rodrigues ◽

Israel Tojal Silva ◽

Tathiane Maistro Malta ◽

...

Keyword(s):

Granzyme B ◽

Treatment Strategies ◽

Cytotoxic Lymphocytes ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Exon 2 ◽

Significant Difference ◽

Novel Treatment Strategies ◽

Brazilian Populations ◽

Afro Brazilian

INTRODUCTION: The cytolysis mediated by granules is one of the most important effector functions of cytotoxic T lymphocytes and natural killer cells. Recently, three single nucleotide polymorphisms (SNPs) were identified at exons 2, 3, and 5 of the granzyme B gene, resulting in a haplotype in which three amino acids of mature protein Q48P88Y245 are changed to R48A88H245, which leads to loss of cytotoxic activity of the protein. In this study, we evaluated the frequency of these polymorphisms in Brazilian populations. METHODS: We evaluated the frequency of these polymorphisms in Brazilian ethnic groups (white, Afro-Brazilian, and Asian) by sequencing these regions. RESULTS: The allelic and genotypic frequencies of SNP 2364A/G at exon 2 in Afro-Brazilian individuals (42.3% and 17.3%) were significantly higher when compared with those in whites and Asians (p < 0.0001 and p = 0.0007, respectively). The polymorphisms 2933C/G and 4243C/T also were more frequent in Afro-Brazilians but without any significant difference regarding the other groups. The Afro-Brazilian group presented greater diversity of haplotypes, and the RAH haplotype seemed to be more frequent in this group (25%), followed by the whites (20.7%) and by the Asians (11.9%), similar to the frequency presented in the literature. CONCLUSIONS: There is a higher frequency of polymorphisms in Afro-Brazilians, and the RAH haplotype was more frequent in these individuals. We believe that further studies should aim to investigate the correlation of this haplotype with diseases related to immunity mediated by cytotoxic lymphocytes, and if this correlation is confirmed, novel treatment strategies might be elaborated.

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Association of the CACNA2D2 gene with schizophrenia in Chinese Han population

PeerJ ◽

10.7717/peerj.8521 ◽

2020 ◽

Vol 8 ◽

pp. e8521

Author(s):

Yingli Fu ◽

Na Zhou ◽

Wei Bai ◽

Yaoyao Sun ◽

Xin Chen ◽

...

Keyword(s):

Calcium Channel ◽

Chinese Women ◽

Han Chinese ◽

Type I ◽

Genotype Distribution ◽

Healthy Controls ◽

Nucleotide Polymorphisms ◽

Chinese Han ◽

Increased Risk ◽

Significant Difference

Background Schizophrenia (SCZ) is a severely complex psychiatric disorder in which ~80% can be explained by genetic factors. Single nucleotide polymorphisms (SNPs) in calcium channel genes are potential genetic risk factors for a spectrum of psychiatric disorders including SCZ. This study evaluated the association between SNPs in the voltage-gated calcium channel auxiliary subunit alpha2delta 2 gene (CACNA2D2) and SCZ in the Han Chinese population of Northeast China. Methods A total of 761 SCZ patients and 775 healthy controls were involved in this case-control study. Three SNPs (rs3806706, rs45536634 and rs12496815) of CACNA2D2 were genotyped by the MALDI-TOF-MS technology. Genotype distribution and allele frequency differences between cases and controls were tested by Chi-square (χ2) in males and females respectively using SPSS 24.0 software. Linkage disequilibrium and haplotype analyses were conducted using Haploview4.2. The false discovery rate correction was utilized to control for Type I error by R3.2.3. Results There was a significant difference in allele frequencies (χ2 = 9.545, Padj = 0.006) and genotype distributions (χ2 = 9.275, Padj = 0.006) of rs45536634 between female SCZ patients and female healthy controls after adjusting for multiple comparisons. Minor allele A (OR = 1.871, 95% CI [1.251–2.798]) and genotype GA + AA (OR = 1.931, 95% CI [1.259–2.963]) were associated with an increased risk of SCZ. Subjects with haplotype AG consisting of rs45536634 and rs12496815 alleles had a higher risk of SCZ (OR = 1.91, 95% CI [1.26–2.90]) compared those with other haplotypes. Conclusions This study provides evidence that CACNA2D2 polymorphisms may influence the susceptibility to SCZ in Han Chinese women.

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Serum total adenosine deaminase activity in Nepalese patients with Rheumatoid Arthritis

Asian Journal of Medical Sciences ◽

10.3126/ajms.v4i2.6208 ◽

2013 ◽

Vol 4 (2) ◽

pp. 30-35

Author(s):

N Gautam ◽

J Archana ◽

R Kumar ◽

LI Singh ◽

RM Sapkota ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Adenosine Deaminase ◽

Healthy Controls ◽

Medical Sciences ◽

Potential Marker ◽

Diagnostic Potential ◽

Clinical Scenarios ◽

Adenosine Deaminase Activity ◽

Significant Difference ◽

Reliable Marker

Objective: Several studies indicate that serum adenosine deaminase (ADA) activity could be a potential marker for the diagnosis of patients with rheumatoid arthritis (RA). However, there has been no such study that could independently verify this finding in Nepali population. The present study therefore aims to measure the total ADA activity in the sera of Nepalese RA patients and verify its diagnostic potential. Materials and Methods: A total of 69 RA patients who visited Universal College of Medical Sciences Teaching Hospital (UCMSTH), Bhairahawa, Nepal for their medical treatment were enrolled for this study. An equal number of age and sex-matched healthy controls were also included in the study. Blood samples were collected from each study subjects and analyzed for serum total ADA, Creactive protein (CRP) and rheumatoid factor (RF). Results: Serum total ADA activity was found to be significantly (p<0.0001) higher (30.0 }10.1 U/L) in all RA patients compared to healthy controls (13.5 } 3.6 U/L). However, no significant difference (p>0.05) in the ADA activity was found between the smokers and non-smoker RA patients. Out of total 69 RA patients, only 16 (23.1%) were positive for CRP and 11 (15.9%) were positive for RF. Conclusion: Measurement of serum total ADA activity could be a reliable marker for the diagnosis of RA in Nepali population with relevant clinical scenarios when there is absence of CRP and RF in the serum. DOI: http://dx.doi.org/10.3126/ajms.v4i2.6208 Asian Journal of Medical Sciences 4(2013) 30-35

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Association of Thr715Pro P-Selectin Gene Polymorphism in Diabetic Retinopathy in North Indian Population: A Prospective Clinical Study

Nepalese Journal of Ophthalmology ◽

10.3126/nepjoph.v13i2.28372 ◽

2021 ◽

Vol 13 (2) ◽

pp. 145-153

Author(s):

Ritika Sharma ◽

Shri Kant ◽

Deepak Mishra ◽

Tanmay Srivastav ◽

Hemendra Singh

Keyword(s):

Diabetic Retinopathy ◽

Clinical Study ◽

Gene Polymorphism ◽

Indian Population ◽

Prospective Clinical Study ◽

Healthy Controls ◽

Independent Factor ◽

North Indian Population ◽

Genotypic Analysis ◽

Significant Difference

Introduction: The aim of this study was to evaluate the role of Thr715Pro P-Selectin gene polymorphism in patients with Diabetic Retinopathy in North Indian population and establish its role in the pathophysiology as an independent factor. Materials and methods: This is a prospective clinical study conducted on 60 patients at a tertiary care centre in North India over a period of eighteen months. Sixty patients satisfying the inclusion criteria were selected from the Vitreoretina clinic in the department. They were categorised equally in three groups namely Diabetics with diabetic retinopathy (DwDR), Diabetics without diabetic retinopathy (DwoDR), and non diabetics. The non-diabetics group was further divided into healthy controls, Hypertensive Retinopathy (HR) and Non-exudative Age Related Macular Degeneration (NEAMD). All the patients underwent complete ophthalmic evaluation and blood samples were drawn for the genetic study with their informed consent. Data was analysed using SPSS software version 16. Results: The genotypic analysis between DwDR, DwoDR and the three subgroup of controls comprising of healthy controls, HR and NEAMD showed that Thr715Pro (A/C) polymorphism prevalence was significantly high in DwDR (p = 0.003) and DwoDR (p = 0.003) compared to healthy controls. No significant difference was noted between DwDR, DwoDR and the HR and NEAMD groups. Conclusion: Thr715Pro P-Selectin gene Polymorphism could not be established as an independent factor in the pathogenesis of diabetic retinopathy, as its association is found with other systemic diseases which create a prothrombotic state.

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Polymorphisms of LHβ and GnRHR genes and their association with the number of embryos recovered in goats

Animal Production Science ◽

10.1071/an13076 ◽

2014 ◽

Vol 54 (8) ◽

pp. 987 ◽

Cited By ~ 1

Author(s):

M. Z. Fu ◽

G. Li ◽

Z. Q. Zhou

Keyword(s):

Polymerase Chain Reaction ◽

Single Nucleotide Polymorphisms ◽

Gene Polymorphism ◽

Corpus Luteum ◽

Nucleotide Polymorphisms ◽

Chain Reaction ◽

Single Strand Conformational Polymorphism ◽

Single Nucleotide ◽

Exon 2 ◽

Polymerase Chain

The objective of the present study was to explore a predictor of superovulation response on the basis of associations between the number of embryos recovered and gene polymorphism. Variation in the goat LHβ and GnRHR genes was investigated using polymerase chain reaction–single-strand conformational polymorphism and DNA sequencing. Two single nucleotide polymorphisms (SNPs) were identified in the 5′-UTR of LHβ gene (A59C, P1 locus) and in the Exon 2 of GnRHR gene (T177A, P6 locus). At the P1 locus in both breeds, the frequencies of one allele were 0.46 and 0.51, respectively. At the P6 locus, the minor allele frequency was 0.23. Associations of both SNPs with the number of embryos recovered and the corpus luteum number were evaluated in Boer and Shaanbei goat breeds. Association analysis showed that both SNPs had significant (P < 0.05) effects on the number of embryos recovered and corpus luteum number. These results indicate that LHβ and GnRHR genes are potential markers for the number of embryos recovered.

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Assessment of Toll Like receptor 2 Gene Polymorphism in Children with B Cell Defects and Respiratory Tract Infections

QJM ◽

10.1093/qjmed/hcaa063.038 ◽

2020 ◽

Vol 113 (Supplement_1) ◽

Author(s):

N A A Mahana ◽

S M Reda ◽

T B Kamel ◽

R A Elfeky ◽

D M Erfan ◽

...

Keyword(s):

Risk Factor ◽

Respiratory Tract ◽

Respiratory Tract Infections ◽

Pulmonary Function Tests ◽

Additional Risk Factor ◽

Healthy Controls ◽

Nucleotide Polymorphisms ◽

Cross Sectional ◽

Significant Difference ◽

Tract Infections

Abstract Acute respiratory tract infections are the most common illnesses in childhood. Respiratory defenses against infection involve a diverse and complex system. Toll-like receptors (TLRs) are a type of pattern recognition receptors (PRRs), recognize pathogen-associated molecular patterns (PAMPs), resulting in initiation of innate immune response and promotion of adaptive immunity. TLR single nucleotide polymorphisms (SNPs) impair the ability to respond properly to TLR ligands and increase susceptibility to infectious or inflammatory diseases. The aim of the work: To examine TLR2 Arginine 677Tryptophan (Arg 677Trp) and Arginine753Glutamine (Arg753Gln) gene polymorphisms in patients with recurrent or chronic respiratory tract infections with or without predominantly antibody deficiency (PAD). Subjects and methods: This cross-sectional case-control study included 30 patients with known PAD with/ or without respiratory tract infections, 20 non-PAD patients with recurrent chest infections and 20 age and sex-matched healthy controls. All children included in the study were subjected to full history taking, complete physical examination and laboratory investigations including CBC, serum immunoglobulins levels and genetic analysis of the TLR2 Arg677Trp and Arg753Gln polymorphisms. Computed tomography (CT) scan of the chest with contrast, pulmonary function tests (PFTs) and Bronchoalveolar lavage (BAL) fluid culture and sensitivity were performed to patients with recurrent and/or chronic chest infections. Results: There was a significant difference in the expression of Arg753Gln polymorphism (p 0.04) between PAD patients with and without recurrent chest infections. Patients with mutant or heterozygote state of this polymorphism had a short diagnosis lag (time elapsed between onset of symptoms and date of diagnosis). There was a significant relationship between this polymorphism and the duration of hospital admission (longer hospital stay in patients with mutant allele). A significant difference between non-PAD patients with recurrent chest infections and healthy controls regarding Arg 677 Trp polymorphism (p 0.04) was elicited. Conclusion: Our results suggest that Arg 677 Trp polymorphism could be a risk factor for increased susceptibility to recurrent and /or chronic respiratory tract infections in patients without PAD, while Arg753Gln polymorphism might be an additional risk factor for severe infections in PAD patients.

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Distribution of apolipoprotein E gene polymorphism in students and in high-educated elderly from Serbia

Genetika ◽

10.2298/gensr1303865m ◽

2013 ◽

Vol 45 (3) ◽

pp. 865-872

Author(s):

Nela Maksimovic ◽

Ivana Novakovic ◽

Vesna Ralic ◽

Elka Stefanova

Keyword(s):

Gene Polymorphism ◽

Apolipoprotein E ◽

Apoe Genotype ◽

Human Populations ◽

Nucleotide Polymorphisms ◽

Gene Encoding ◽

Genetic Determination ◽

Asian Populations ◽

Significant Difference ◽

Older Populations

Apolipoprotein E (ApoE) play important role in lipid metabolism and in processes of remodeling and reparation in central nervous system. Three common ApoE isoforms, ApoE2, ApoE3 and ApoE4, show strong genetic determination by ?2, ?3, and ?4 allele. In human genome gene encoding Apolipoprotein E (APOE) is located on cromosome 19, and ?2/?3/?4 haplotype system is defined by 2 non-synonymous single nucleotide polymorphisms (SNPs) in the APOE exon 4. The frequency of the three APOE alleles and corresponding genotypes varies across human populations, with possible clinical implications. At least, variable distribution of ?4 allele may contribute to the regional risk of cardiovascular and Alzheimer?s diseases. Allele-frequency comparisons between younger and older populations suggest an effect of APOE on mortality, but these data are not consistently confirmed. In the present study we have analyzed the distribution of APOE gene polymorphism in a group of University students and retained University professors living in Serbia. After DNA extraction from peripheral blood samples, the APOE genotype was determined by polymerase chain reaction (PCR) followed with HhaI restriction digestion. We found no statistically significant difference in alleles and genotypes distribution between younger and elder group of participants. Also, there was no significant difference compared to APOE data previously obtained in YUSAD cohort of healthy school children (15 y of age) from different regions of Serbia. In both of our groups, as well as in YUSAD cohort, frequency of APOE ?4 allele was <10%. The observed frequencies are lower than in neighboring countries, but similar with Spanish data and some Asian populations. Our results do not support important role of APOE ?4 in the morbidity and mortality in Serbian population, but gene-environmental-social interactions should be considered.

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Association of Leptin Gene Polymorphisms with Rheumatoid Arthritis in a Chinese Population

BioMed Research International ◽

10.1155/2020/3789319 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7

Author(s):

Sha-Sha Tao ◽

Yi-Lin Dan ◽

Guo-Cui Wu ◽

Qin Zhang ◽

Tian-Ping Zhang ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Chinese Population ◽

Clinical Manifestations ◽

Enzyme Linked Immunosorbent Assay ◽

Healthy Controls ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Genotype Frequencies ◽

Significant Difference ◽

Plasma Leptin

Background. Recently, increasing studies have revealed that leptin is involved in the development of rheumatoid arthritis (RA). This study is aimed at exploring the association of leptin gene single nucleotide polymorphisms (SNPs) with susceptibility to RA in a Chinese population. Methods. We recruited 600 RA patients and 600 healthy controls from a Chinese population and analyzed their three leptin SNPs (rs10244329, rs2071045, and rs2167270) using the improved Multiplex Ligase Detection Reaction (iMLDR) assays. The associations of these SNPs with clinical manifestations of RA were also analyzed. Enzyme-linked immunosorbent assay (ELISA) was performed for plasma leptin determination. Results. No significant difference in either allele or genotype frequencies of these three SNPs between RA patients and healthy controls was observed (all P > 0.05 ). Association between the genotype effects of dominant, recessive models was also not found (all P > 0.05 ). No significant difference in plasma leptin levels was detected between RA patients and controls ( P > 0.05 ). Conclusion. Leptin gene (rs10244329, rs2071045, and rs2167270) polymorphisms are not associated with RA genetic susceptibility and its clinical features in the Chinese population.

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