scholarly journals The frequencies of autoimmunity risk alleles of some genes in Belarus population

2010 ◽  
Vol 8 (1) ◽  
pp. 50-58
Author(s):  
Elena A Aksenova ◽  
Tatiana N Pokladok ◽  
Dina V Boiko ◽  
Nina G Danilenko
Keyword(s):  
T Lymphocyte ◽  
Protein Tyrosine Phosphatase ◽  
Risk Allele ◽  
Cytotoxic T Lymphocyte ◽  
Tyrosine Phosphatase ◽  
Allele Frequencies ◽  
Protective Allele ◽  
Risk Alleles ◽  
Genotype And Allele Frequencies ◽  
Allele Combination

The population genotype and allele frequencies of +49A/G cytotoxic T-lymphocyte-associated antigen-4 (CTLA4); C1858T protein tyrosine phosphatase gene (PTPN22); –23HphIА/T insulin gene (INS) loci in native Belarusians from 6 ethnogeographic regions were estimated. The frequencies of risk allele homozygotes were: +49G CTLA4 — 17,3%; –23HphIА INS 50,7% — 1858Т PTPN22 — 4,1%. 5 individuals out of 662 investigated were risk homozygotes for all three genes, 21 were homozygotes with protective allele combination. The uniformity of genotypes and alleles distribution of investigated locuses across Belarus regions was demonstrated. 

scholarly journals Metaanalysis of the Association of Smoking andPTPN22R620W Genotype on Autoantibody Status and Radiological Erosions in Rheumatoid Arthritis

2013 ◽  
Vol 40 (7) ◽  
pp. 1048-1053 ◽  
Author(s):  
Lyndsey H. Taylor ◽  
Sarah Twigg ◽  
Jane Worthington ◽  
Paul Emery ◽  
Ann W. Morgan ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Protein Tyrosine Phosphatase ◽  
Fixed Effects ◽  
Risk Allele ◽  
Smoking Status ◽  
Tyrosine Phosphatase ◽  
Risk Alleles ◽  
Peptide Antibody ◽  
Autoantibody Status ◽  
Acpa Status

Objective.To investigate the interrelationships among smoking, protein tyrosine phosphatase non-receptor 22 (PTPN22) R620W (rs2476601) genotype, and anticitrullinated peptide antibody (ACPA) status; and among smoking,PTPN22R620W genotype, and presence of bone erosions overall and separately by ACPA status in patients with rheumatoid arthritis (RA).Methods.Six studies totaling 2680 patients with RA were included in a Mantel-Haenszel fixed-effects metaanalysis investigating ACPA status and up to 8 studies totaling 3172 patients with RA were included in a Mantel-Haenszel fixed-effects metaanalysis investigating presence of erosive damage.Results.Evidence was found for an increase in the odds of ACPA positivity for ever smoking (OR 1.56, 95% CI 1.28–1.90, p = 8.5 × 10−6), carriage of at least 1 of thePTPN22risk alleles (OR 1.50, 95% CI 1.13–2.00, p = 5.5 × 10−3) and both ever smoking and carriage of at least 1 of thePTPN22risk alleles (OR 2.22, 95% CI 1.69–2.91, p = 8.3 × 10−9). There was no evidence of an association between presence of erosive damage and smoking status or carriage ofPTPN22risk alleles when analyzed overall or separately by ACPA status.Conclusion.This metaanalysis indicates that both smoking and thePTPN22risk allele are associated with the risk of ACPA positivity. There was insufficient evidence to establish a relationship in either direction betweenPTPN22and smoking with erosive damage, despite evidence that ACPA positivity is associated with erosive damage.

scholarly journals The Epidemiology and Genetics of Hyperuricemia and Gout across Major Racial Groups: A Literature Review and Population Genetics Secondary Database Analysis

2021 ◽  
Vol 11 (3) ◽  
pp. 231
Author(s):  
Faven Butler ◽  
Ali Alghubayshi ◽  
Youssef Roman
Keyword(s):  
Literature Review ◽  
Risk Allele ◽  
Statistical Significance ◽  
Elevated Serum ◽  
The United States ◽  
Allele Frequencies ◽  
Racial Groups ◽  
1000 Genomes Project ◽  
1000 Genomes ◽  
Risk Alleles

Gout is an inflammatory condition caused by elevated serum urate (SU), a condition known as hyperuricemia (HU). Genetic variations, including single nucleotide polymorphisms (SNPs), can alter the function of urate transporters, leading to differential HU and gout prevalence across different populations. In the United States (U.S.), gout prevalence differentially affects certain racial groups. The objective of this proposed analysis is to compare the frequency of urate-related genetic risk alleles between Europeans (EUR) and the following major racial groups: Africans in Southwest U.S. (ASW), Han-Chinese (CHS), Japanese (JPT), and Mexican (MXL) from the 1000 Genomes Project. The Ensembl genome browser of the 1000 Genomes Project was used to conduct cross-population allele frequency comparisons of 11 SNPs across 11 genes, physiologically involved and significantly associated with SU levels and gout risk. Gene/SNP pairs included: ABCG2 (rs2231142), SLC2A9 (rs734553), SLC17A1 (rs1183201), SLC16A9 (rs1171614), GCKR (rs1260326), SLC22A11 (rs2078267), SLC22A12 (rs505802), INHBC (rs3741414), RREB1 (rs675209), PDZK1 (rs12129861), and NRXN2 (rs478607). Allele frequencies were compared to EUR using Chi-Square or Fisher’s Exact test, when appropriate. Bonferroni correction for multiple comparisons was used, with p < 0.0045 for statistical significance. Risk alleles were defined as the allele that is associated with baseline or higher HU and gout risks. The cumulative HU or gout risk allele index of the 11 SNPs was estimated for each population. The prevalence of HU and gout in U.S. and non-US populations was evaluated using published epidemiological data and literature review. Compared with EUR, the SNP frequencies of 7/11 in ASW, 9/11 in MXL, 9/11 JPT, and 11/11 CHS were significantly different. HU or gout risk allele indices were 5, 6, 9, and 11 in ASW, MXL, CHS, and JPT, respectively. Out of the 11 SNPs, the percentage of risk alleles in CHS and JPT was 100%. Compared to non-US populations, the prevalence of HU and gout appear to be higher in western world countries. Compared with EUR, CHS and JPT populations had the highest HU or gout risk allele frequencies, followed by MXL and ASW. These results suggest that individuals of Asian descent are at higher HU and gout risk, which may partly explain the nearly three-fold higher gout prevalence among Asians versus Caucasians in ambulatory care settings. Furthermore, gout remains a disease of developed countries with a marked global rising.

scholarly journals How genetic disease risks can be misestimated across global populations

2017 ◽  
Author(s):  
Michelle S Kim ◽  
Kane P Patel ◽  
Andrew K Teng ◽  
Ali J Berens ◽  
Joseph Lachance
Keyword(s):  
Genetic Disease ◽  
Risk Allele ◽  
Association Studies ◽  
Allele Frequencies ◽  
Risk Scores ◽  
Genome Wide Association Studies ◽  
Whole Genome ◽  
Risk Alleles ◽  
Disease Associations ◽  
Disease Risks

AbstractBackgroundAccurate assessment of health disparities requires unbiased knowledge of genetic risks in different populations. Unfortunately, most genome-wide association studies use genotyping arrays and European samples. Here, we integrate whole genome sequence data from global populations, results from thousands of GWAS, and extensive computer simulations to identify how genetic disease risks can be misestimated.ResultsIn contrast to null expectations, we find that risk allele frequencies at known disease loci are significantly different for African populations compared to other continents. Strikingly, ancestral risk alleles are found at 9.51% higher frequency in Africa and derived risk alleles are found at 5.40% lower frequency in Africa. By simulating GWAS with different study populations, we find that non-African cohorts yield disease associations that have biased allele frequencies and that African cohorts yield disease associations that are relatively free of bias. We also find empirical evidence that genotyping arrays and SNP ascertainment bias contribute to continental differences in risk allele frequencies. Because of these causes, polygenic risk scores can be grossly misestimated for individuals of African descent. Importantly, continental differences in risk allele frequencies are only moderately reduced if GWAS use whole genome sequences and hundreds of thousands of cases and controls. Finally, comparisons between uncorrected and corrected genetic risk scores reveal the benefits of considering whether risk alleles are ancestral or derived.ConclusionsOur results imply that caution must be taken when extrapolating GWAS results from one population to predict disease risks in another population.

scholarly journals The Epidemiology and Genetics of Hyperuricemia and Gout Across Major Racial Groups: A literature Review and Population Genetics Secondary Data Analysis

2021 ◽  
Author(s):  
Faven Butler ◽  
Ali Alghubayshi ◽  
Youssef Malak Roman
Keyword(s):  
Literature Review ◽  
Risk Allele ◽  
Statistical Significance ◽  
Elevated Serum ◽  
The United States ◽  
Allele Frequencies ◽  
Racial Groups ◽  
1000 Genomes Project ◽  
1000 Genomes ◽  
Risk Alleles

Abstract BackgroundGout is an inflammatory condition caused by elevated serum urate (SU), a condition known as hyperuricemia (HU). Genetic variations, including single nucleotide polymorphisms (SNPs), can alter the function of urate transporters, leading to differential HU and gout prevalence across different populations. In the United States (U.S.)., gout prevalence differentially affects certain racial groups. The objective of this proposed analysis is to compare the frequency of urate-related genetic risk alleles between Europeans (EUR) and the following major racial groups: Africans in Southwest U.S. (ASW), Han-Chinese (CHS), Japanese (JPT), and Mexican (MXL) from the 1000 Genomes Project. MethodsEnsembl genome browser of the 1000 Genomes Project was used to conduct cross-population allele frequency comparisons of 11 SNPs across 11 genes, physiologically involved and significantly associated with SU levels and gout risk. Gene/SNP pairs included: ABCG2 (rs2231142), SLC2A9 (rs734553), SLC17A1 (rs1183201), SLC16A9 (rs1171614), GCKR (rs1260326), SLC22A11 (rs2078267), SLC22A12 (rs505802), INHBC (rs3741414), RREB1 (rs675209), PDZK1 (rs12129861), and NRXN2 (rs478607). Allele frequencies were compared to EUR using Chi-Square or Fisher's Exact test, when appropriate. Bonferroni correction for multiple comparisons was used, with p<0.005 for statistical significance. Risk alleles were defined as the allele that is associated with baseline or higher HU and gout risks. The cumulative HU or gout risk allele index of the 11 SNPs was estimated for each population. The prevalence of HU and gout in U.S. and non-US populations was evaluated using a literature review.ResultsCompared with EUR, the SNP frequencies of 7/11 in ASW, 9/11 in MXL, 9/11 JPT, and 11/11 CHS were significantly different. HU or gout risk allele indices were 5, 6, 9, and 11 in ASW, MXL, CHS, and JPT, respectively. Out of the 11 SNPs, the percentage of risk alleles in CHS and JPT was 100%. Compared to non-US populations, the prevalence of HU and gout appear to be higher in western world countries.ConclusionsCompared with EUR, CHS and JPT populations had the highest HU or gout risk allele frequencies, followed by MXL and ASW. These results suggest that individuals of Asian descent are at higher HU and gout risk, which may partly explain the 2.7-fold higher gout prevalence among Asians versus Caucasians in ambulatory care settings. Furthermore, gout remains a disease of developed countries with a marked global rising.

scholarly journals Cytotoxic T Lymphocyte Antigen 4 Is Induced in the Thymus upon In Vivo Activation and Its Blockade Prevents Anti-CD3–mediated Depletion of  Thymocytes

1998 ◽  
Vol 188 (7) ◽  
pp. 1239-1246 ◽  
Author(s):  
Corrado M. Cilio ◽  
Michael R. Daws ◽  
Anna Malashicheva ◽  
Charles L. Sentman ◽  
Dan Holmberg
Keyword(s):  
T Cell ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Tyrosine Phosphatase ◽  
Costimulatory Molecule ◽  
Sh2 Domain ◽  
Double Positive ◽  
Cell Repertoire ◽  
Lymphocyte Antigen

The development of a normal T cell repertoire in the thymus is dependent on the interplay between signals mediating cell survival (positive selection) and cell death (negative selection or death by neglect). Although the CD28 costimulatory molecule has been implicated in this process, it has been difficult to establish a role for the other major costimulatory molecule, cytotoxic T lymphocyte antigen (CTLA)-4. Here we report that in vivo stimulation through the T cell receptor (TCR)–CD3 complex induces expression of CTLA-4 in thymocytes and leads to the association of CTLA-4 with the SH2 domain–containing phosphatase (SHP)-2 tyrosine phosphatase. Moreover, intrathymic CTLA-4 blockade dramatically inhibits anti-CD3–mediated depletion of CD4+CD8+ double positive immature thymocytes. Similarly, anti-CD3–mediated depletion of CD4+CD8+ double positive cells in fetal thymic organ cultures could also be inhibited by anti–CTLA-4 antibodies. Thus, our data provide evidence for a role of CTLA-4 in thymic selection and suggest a novel mechanism contributing to the regulation of TCR-mediated selection of T cell repertoires.

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