Relationship between rs4349859 and rs116488202 polymorphisms close to MHC-I region and serum urate levels in patients with gout.
Gout
Inflammatory diseases
MHC-1
Serum urate
Single nucleotide polymorphisms
Journal
Molecular biology reports
ISSN: 1573-4978
Titre abrégé: Mol Biol Rep
Pays: Netherlands
ID NLM: 0403234
Informations de publication
Date de publication:
May 2023
May 2023
Historique:
received:
09
11
2022
accepted:
23
02
2023
medline:
1
5
2023
pubmed:
22
3
2023
entrez:
21
3
2023
Statut:
ppublish
Résumé
Gout is the most common inflammatory rheumatic disease and elevated levels of serum urate (SU) are the main cause for its development. Major histocompatibility complex class 1 (MHC-1) plays an important role in the development of multiple inflammatory diseases; however, there is little evidence of its involvement in gout. The present study focused on evaluating the association of the rs4349859 and rs116488202 single nucleotide polymorphisms (SNPs) close to the MHC-1 region in patients with gout. One hundred and seventy-six individuals of Mexican origin were included, of which 81 were patients with primary gout and 95 were healthy controls. The rs4349859 and rs116488202 SNPs were genotyped using TaqMan probes by allelic discrimination by real-time PCR. Serum concentrations of biochemical parameters were measured with enzymatic methods. Descriptive statistics were applied and P-values < 0.05 were considered significant. It was observed that the rs4349859 and rs116488202 SNPs showed significant association with the risk of gout (OR = 146, 95%CI = 44.8-480.2, P < 0.01; OR = 2885, 95%CI = 265-31398, P < 0.01, respectively). Our results also showed significantly higher serum SU levels in gout patients with respect to controls (P < 0.01) in the carriers of the GA genotype compared with the GG genotype of the rs4349859 variant, and in the carriers of the CT genotype compared with the CC genotype of the rs116488202 variant. The study revealed that rs4349859 and rs116488202 SNPs close to MHC-I region confers strong susceptibility to gout in Mexican population, and the heterozygous genotypes of both were associated with higher levels of SU.
Sections du résumé
BACKGROUND
BACKGROUND
Gout is the most common inflammatory rheumatic disease and elevated levels of serum urate (SU) are the main cause for its development. Major histocompatibility complex class 1 (MHC-1) plays an important role in the development of multiple inflammatory diseases; however, there is little evidence of its involvement in gout. The present study focused on evaluating the association of the rs4349859 and rs116488202 single nucleotide polymorphisms (SNPs) close to the MHC-1 region in patients with gout.
METHODS AND RESULTS
RESULTS
One hundred and seventy-six individuals of Mexican origin were included, of which 81 were patients with primary gout and 95 were healthy controls. The rs4349859 and rs116488202 SNPs were genotyped using TaqMan probes by allelic discrimination by real-time PCR. Serum concentrations of biochemical parameters were measured with enzymatic methods. Descriptive statistics were applied and P-values < 0.05 were considered significant. It was observed that the rs4349859 and rs116488202 SNPs showed significant association with the risk of gout (OR = 146, 95%CI = 44.8-480.2, P < 0.01; OR = 2885, 95%CI = 265-31398, P < 0.01, respectively). Our results also showed significantly higher serum SU levels in gout patients with respect to controls (P < 0.01) in the carriers of the GA genotype compared with the GG genotype of the rs4349859 variant, and in the carriers of the CT genotype compared with the CC genotype of the rs116488202 variant.
CONCLUSION
CONCLUSIONS
The study revealed that rs4349859 and rs116488202 SNPs close to MHC-I region confers strong susceptibility to gout in Mexican population, and the heterozygous genotypes of both were associated with higher levels of SU.
Identifiants
pubmed: 36943604
doi: 10.1007/s11033-023-08359-8
pii: 10.1007/s11033-023-08359-8
doi:
Substances chimiques
Uric Acid
268B43MJ25
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4367-4374Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature B.V.
Références
Ben Salem C, Slim R, Fathallah N, Hmouda H (2017) Drug-induced hyperuricaemia and gout. Rheumatology (Oxford) 56(5):679–688. https://doi.org/10.1093/rheumatology/kew293
doi: 10.1093/rheumatology/kew293
pubmed: 27498351
Dalbeth N, Merriman TR, Stamp LK (2016) Gout Lancet 388(10055):2039–2052. https://doi.org/10.1016/S0140-6736(16)00346-9
doi: 10.1016/S0140-6736(16)00346-9
pubmed: 27112094
Singh JA, Gaffo A (2020) Gout epidemiology and comorbidities. Semin Arthritis Rheum 50(3S):S11–S16. https://doi.org/10.1016/j.semarthrit.2020.04.008
doi: 10.1016/j.semarthrit.2020.04.008
pubmed: 32620196
Galozzi P, Bindoli S, Doria A, Oliviero F, Sfriso P (2021) Autoinflammatory features in Gouty Arthritis. J Clin Med 10(10):1880. https://doi.org/10.3390/jcm10091880
doi: 10.3390/jcm10091880
pubmed: 33926105
pmcid: 8123608
Abou-Elela A (2017) Epidemiology, pathophysiology, and management of uric acid urolithiasis: a narrative review. J Adv Res 8(5):513–527. https://doi.org/10.1016/j.jare.2017.04.005
doi: 10.1016/j.jare.2017.04.005
pubmed: 28748117
pmcid: 5512151
Ragab G, Elshahaly M, Bardin T (2017) Gout: an old disease in new perspective - A review. J Adv Res 8(5):495–511. https://doi.org/10.1016/j.jare.2017.04.008
doi: 10.1016/j.jare.2017.04.008
pubmed: 28748116
pmcid: 5512152
Eckenstaler R, Benndorf RA (2021) The role of ABCG2 in the pathogenesis of primary hyperuricemia and Gout-An update. Int J Mol Sci 22(13):6678. https://doi.org/10.3390/ijms22136678
doi: 10.3390/ijms22136678
pubmed: 34206432
pmcid: 8268734
Dalbeth N, Gosling AL, Gaffo A, Abhishek A (2021) Gout Lancet 397(10287):1843–1855. https://doi.org/10.1016/S0140-6736(21)00569-9
doi: 10.1016/S0140-6736(21)00569-9
pubmed: 33798500
Stiburkova B, Miyata H, Závada J, Tomčík M, Pavelka K, Storkanova G et al (2016) Novel dysfunctional variant in ABCG2 as a cause of severe tophaceous gout: biochemical, molecular genetics and functional analysis. Rheumatology (Oxford) 55(1):191–194. https://doi.org/10.1093/rheumatology/kev350
doi: 10.1093/rheumatology/kev350
pubmed: 26428519
Yang Q, Guo CY, Cupples LA, Levy D, Wilson PWF, Fox CS (2005) Genome-wide search for genes affecting serum uric acid levels: the Framingham Heart Study. Metabolism 54(11):1435-41. https://doi.org/10.1016/j.metabol.2005.05.007
Lin CY, Chang YS, Liu TY, Huang CH, Chung CC, Chen YC et al (2022) Genetic contributions to female gout and hyperuricemia using genome-wide association study and polygenic risk score analyses. Rheumatology (Oxford) 2022:keac369. https://doi.org/10.1093/rheumatology/keac369
Merriman TR (2015) An update on the genetic architecture of hyperuricemia and gout. Arthritis Res Ther 17(1):98. https://doi.org/10.1186/s13075-015-0609-2
doi: 10.1186/s13075-015-0609-2
pubmed: 25889045
pmcid: 4392805
Choi HK, Zhu Y, Mount DB (2010) Genetics of gout. Curr Opin Rheumatol 22(2):144–151. https://doi.org/10.1097/BOR.0b013e32833645e8
doi: 10.1097/BOR.0b013e32833645e8
pubmed: 20110790
Punzi L, Scanu A, Galozzi P, Luisetto R, Spinella P, Scirè CA et al (2020) One year in review 2020: gout. Clin Exp Rheumatol 38(5):807–821
pubmed: 33034561
Fernández-Torres J, Martínez-Nava GA, Martínez-Flores K, Sánchez-Sánchez R, Jara LJ, Zamudio-Cuevas Y (2022) The interplay between HLA-B and NLRP3 polymorphisms may be associated with the genetic susceptibility of gout. Mol Biol Rep 2022 Sep 3. https://doi.org/10.1007/s11033-022-07895-z
Neogi T, Jansen TL, Dalbeth N, Fransen J, Schumacher HR, Berendsen D et al (2015) 2015 gout classification criteria: an American College of Rheumatology/European League against Rheumatism collaborative initiative. Ann Rheum Dis 74(10):1789–1798. https://doi.org/10.1136/annrheumdis-2015-208237
doi: 10.1136/annrheumdis-2015-208237
pubmed: 26359487
de Oliveira EP, Burini RC (2012) High plasma uric acid concentration: causes and consequences. Diabetol Metab Syndr 4:12. https://doi.org/10.1186/1758-5996-4-12
doi: 10.1186/1758-5996-4-12
pubmed: 22475652
pmcid: 3359272
Katsiki N, Dimitriadis GD, Mikhailidis DP (2021) Serum uric acid and diabetes: from pathophysiology to Cardiovascular Disease. Curr Pharm Des 27(16):1941–1951. https://doi.org/10.2174/1381612827666210104124320
doi: 10.2174/1381612827666210104124320
pubmed: 33397230
Saito Y, Tanaka A, Node K, Kobayashi Y (2021) Uric acid and cardiovascular disease: a clinical review. J Cardiol 78(1):51–57. https://doi.org/10.1016/j.jjcc.2020.12.013
doi: 10.1016/j.jjcc.2020.12.013
pubmed: 33388217
Dong Z, Zhou J, Jiang S, Li Y, Zhao D, Yang C et al (2017) Effects of multiple genetic loci on the pathogenesis from serum urate to gout. Sci Rep 7:43614. https://doi.org/10.1038/srep43614
doi: 10.1038/srep43614
pubmed: 28252667
pmcid: 5333621
Nakatochi M, Kanai M, Nakayama A, Hishida A, Kawamura Y, Ichihara S et al (2019) Genome-wide meta-analysis identifies multiple novel loci associated with serum uric acid levels in japanese individuals. Commun Biol 2:115. https://doi.org/10.1038/s42003-019-0339-0
doi: 10.1038/s42003-019-0339-0
pubmed: 30993211
pmcid: 6453927
Boocock J, Leask M, Okada Y, Asian Genetic Epidemiology Network (AGEN) Consortium, Matsuo H, Kawamura Y et al (2020) Genomic dissection of 43 serum urate-associated loci provides multiple insights into molecular mechanisms of urate control. Hum Mol Genet 29(6):923–943. https://doi.org/10.1093/hmg/ddaa013
doi: 10.1093/hmg/ddaa013
pubmed: 31985003
Sotnik D, Bielska K (1978) HLA antigens in gouty patients. Arch Immunol Ther Exp (Warsz) 26(1–6):213–215
pubmed: 749772
Cassim B, Mody GM, Deenadayalu VK, Hammond MG (1994) Gout in black South Africans: a clinical and genetic study. Ann Rheum Dis 53(11):759–762. https://doi.org/10.1136/ard.53.11.759
doi: 10.1136/ard.53.11.759
pubmed: 7826138
pmcid: 1005458
Mituszova M, Judák A, Poór G, Gyódi E, Stenszky V (1992) Clinical and family studies in hungarian patients with gout. Rheumatol Int 12(5):165–168. https://doi.org/10.1007/BF00302147
doi: 10.1007/BF00302147
pubmed: 1290017
Hsu TW, Lee PS, Nfor ON, Lee CL, Chen PH, Tantoh DM et al (2019) The Interaction between sex and hyperlipidemia on gout risk is modulated by HLA-B polymorphic variants in adult taiwanese. Genes (Basel) 10(3):246. https://doi.org/10.3390/genes10030246
doi: 10.3390/genes10030246
pubmed: 30934611
Toledo-Stuardo K, Ribeiro CH, Canals A, Morales M, Gárate V, Rodríguez-Siza J et al (2021) Major histocompatibility Complex Class I-Related Chain A (MICA) allelic Variants Associate with susceptibility and prognosis of gastric Cancer. Front Immunol 12:645528. https://doi.org/10.3389/fimmu.2021.645528
doi: 10.3389/fimmu.2021.645528
pubmed: 33868281
pmcid: 8045969
Risti M, Bicalho MD (2017) MICA and NKG2D: is there an impact on kidney transplant outcome? Front Immunol 8:179. https://doi.org/10.3389/fimmu.2017.00179
doi: 10.3389/fimmu.2017.00179
pubmed: 28289413
pmcid: 5326783
Choy MK, Phipps ME (2010) MICA polymorphism: biology and importance in immunity and disease. Trends Mol Med 16(3):97–106. https://doi.org/10.1016/j.molmed.2010.01.002
doi: 10.1016/j.molmed.2010.01.002
pubmed: 20153697
Wang K, Cadzow M, Bixley M, Leask MP, Merriman ME, Yang Q et al (2022) A Polynesian-specific copy number variant encompassing the MHC Class I Polypeptide-related Sequence A (MICA) gene associates with gout. Hum Mol Genet 2022:ddac094. https://doi.org/10.1093/hmg/ddac094
Wang J, Liu K, Xiao T, Liu P, Prinz RA, Xu X (2022) Uric acid accumulation in DNA-damaged tumor cells induces NKG2D ligand expression and antitumor immunity by activating TGF-β-activated kinase 1. Oncoimmunology 11(1):2016159. https://doi.org/10.1080/2162402X.2021.2016159
doi: 10.1080/2162402X.2021.2016159
pubmed: 35154904
pmcid: 8837239
Xu X, Rao GS, Groh V, Spies T, Gattuso P, Kaufman HL et al (2011) Major histocompatibility complex class I-related chain A/B (MICA/B) expression in tumor tissue and serum of pancreatic cancer: role of uric acid accumulation in gemcitabine-induced MICA/B expression. BMC Cancer 11:194. https://doi.org/10.1186/1471-2407-11-194
doi: 10.1186/1471-2407-11-194
pubmed: 21605422
pmcid: 3118197
Xu X, Rao G, Li Y (2016) Xanthine oxidoreductase is required for genotoxic stress-induced NKG2D ligand expression and gemcitabine-mediated antitumor activity. Oncotarget 7(37):59220–59235. https://doi.org/10.18632/oncotarget.11042
doi: 10.18632/oncotarget.11042
pubmed: 27494876
pmcid: 5312307
Glas J, Martin K, Brünnler G, Kopp R, Folwaczny C, Weiss EH et al (2001) MICA, MICB and C1_4_1 polymorphism in Crohn’s disease and ulcerative colitis. Tissue Antigens 58(4):243–249. https://doi.org/10.1034/j.1399-0039.2001.580404.x
doi: 10.1034/j.1399-0039.2001.580404.x
pubmed: 11782275
Frommer L, Kahaly GJ (2021) Type 1 diabetes and autoimmune thyroid disease-the genetic link. Front Endocrinol (Lausanne) 12:618213. https://doi.org/10.3389/fendo.2021.618213
doi: 10.3389/fendo.2021.618213
pubmed: 33776915
Wielińska J, Tarassi K, Iwaszko M, Kościńska K, Wysoczańska B, Mole E et al (2021) Shared epitope and polymorphism of MICA and NKG2D encoding genes in Greek and Polish patients with rheumatoid arthritis. Cent Eur J Immunol 46(1):92–98. https://doi.org/10.5114/ceji.2021.104425
doi: 10.5114/ceji.2021.104425
pubmed: 33897289
pmcid: 8056341
Lee YH, Bae SC, Kim JH, Song GG (2015) Meta-analysis of the association between functional MICA-TM polymorphisms and systemic lupus erythematosus, rheumatoid arthritis and ankylosing spondylitis. Z Rheumatol 74(2):146–152. https://doi.org/10.1007/s00393-014-1409-9
doi: 10.1007/s00393-014-1409-9
pubmed: 25060517
Zhu W, Deng Y, Wang J, Guo X, Ding W, Chao J et al (2019) MICA*049, not MICA*009, is associated with Behçet’s disease in a chinese population. Sci Rep 9(1):10856. https://doi.org/10.1038/s41598-019-47289-z
doi: 10.1038/s41598-019-47289-z
pubmed: 31350414
pmcid: 6659628
Méndez-Salazar EO, Vázquez-Mellado J, Casimiro-Soriguer CS, Dopazo J, Çubuk C, Zamudio-Cuevas Y et al (2021) Taxonomic variations in the gut microbiome of gout patients with and without tophi might have a functional impact on urate metabolism. Mol Med 27(1):50. https://doi.org/10.1186/s10020-021-00311-5
doi: 10.1186/s10020-021-00311-5
pubmed: 34030623
pmcid: 8142508
Zhang W, Wang T, Guo R, Cui W, Yu W, Wang Z et al (2022) Variation of serum uric acid is Associated with gut microbiota in patients with diabetes Mellitus. Front Cell Infect Microbiol 11:761757. https://doi.org/10.3389/fcimb.2021.761757
doi: 10.3389/fcimb.2021.761757
pubmed: 35118005
pmcid: 8803748
Sharip A, Kunz J (2020) Understanding the pathogenesis of Spondyloarthritis. Biomolecules 10(10):1461. https://doi.org/10.3390/biom10101461
doi: 10.3390/biom10101461
pubmed: 33092023
pmcid: 7588965