Association between genotypes of \(\textit{TLR4}\) gene rs2149356 polymorphism and serum level of il-6 in Vietnamese patients with gout


  • Nguyen Thi Xuan Institute of Genome Research, VAST, Vietnam
  • Le Thuy Ha 103 Hospital, Vietnam Military Medical University, Ha Dong, Hanoi, Vietnam
  • Dang Thanh Chung Vietnam Military Medical University, Hanoi, Vietnam



Cytokine, ELISA, gout, DNA sequencing, TLR4


Gout is an inflammatory type of arthritis caused by the deposition of crystals of monosodium urate monohydrate (MSU) in the joints. The arthritis is mediated by the release of pro-inflammatory cytokines including IL-1β, TNF-α and IL-6 by leukocytes including macrophages. Toll-like receptor (TLR)4 is expressed in the immune cells to initiate immune response by inducing activation of signaling molecules involved in the transcription of nuclear genes. In this study, mutational analysis of TLR4 gene was examined to determine the prevalence of gene polymorphism in Vietnamese patients with gout. Molecular analysis of this gene was investigated by PCR amplification and direct DNA sequencing. Level of serum cytokines was measured by ELISA. As a result, no significant difference in frequency of TLR4 gene rs2149356 polymorphism was observed between the patient and control groups. Importantly, level of IL-6 was significantly higher in patients carrying CG genotype as compared with patients carrying TG and TT genotypes of TLR4 gene rs2149356 polymorphism and the patients carrying GG genotype exhibited higher IL-6 level than healthy individuals. The GG genotype of TLR4 gene rs2149356 polymorphism in gout patients were sensitive to IL6-induced inflammatory response. The effect is expected to affect the immune response to treatment for gout patients.


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Aderem A. & Ulevitch R. J., 2000. Toll-like receptors in the induction of the innate immune response. Nature, 406: 782−787.

Cavalcanti N. G., Marques C. D., Lins E. L. T. U., Pereira M. C., Rego M. J., Duarte A. L., Pitta Ida R. & Pitta M. G., 2016. Cytokine Profile in Gout: Inflammation Driven by IL-6 and IL-18? Immunol Invest, 45: 383−395.

Crisan T. O., Cleophas M. C., Oosting M., Lemmers H., Toenhake-Dijkstra H., Netea M. G., Jansen T. L. & Joosten L. A., 2016. Soluble uric acid primes TLR-induced proinflammatory cytokine production by human primary cells via inhibition of IL-1Ra. Ann Rheum Dis, 75: 755−762.

Flynn T. J., Phipps-Green A., Hollis-Moffatt J. E., Merriman M. E., Topless R., Montgomery G., Chapman B., Stamp L. K., Dalbeth N. & Merriman T. R., 2013. Association analysis of the SLC22A11 (organic anion transporter 4) and SLC22A12 (urate transporter 1) urate transporter locus with gout in New Zealand case-control sample sets reveals multiple ancestral-specific effects. Arthritis research & therapy, 15: 1−11.

Hollingsworth J. W., Whitehead G. S., Lin K. L., Nakano H., Gunn M. D., Schwartz D. A. & Cook D.N., 2006. TLR4 signaling attenuates ongoing allergic inflammation. J Immunol, 176: 5856−5862.

Hurba O., Mancikova A., Krylov V., Pavlikova M., Pavelka K. & Stiburkova B., 2014. Complex analysis of urate transporters SLC2A9, SLC22A12 and functional characterization of non-synonymous allelic variants of GLUT9 in the Czech population: no evidence of effect on hyperuricemia and gout. PloS one, 9: 1−10.

Itahana Y., Han R., Barbier S., Lei Z., Rozen S. & Itahana K., 2015. The uric acid transporter SLC2A9 is a direct target gene of the tumor suppressor p53 contributing to antioxidant defense. Oncogene, 34: 1799−1810.

Kawamura Y., Matsuo H., Chiba T., Nagamori S., Nakayama A., Inoue H., Utsumi Y., Oda T., Nishiyama J., Kanai Y. & Shinomiya N., 2011. Pathogenic GLUT9 mutations causing renal hypouricemia type 2 (RHUC2). Nucleosides, Nucleotides & Nucleic Acids, 30: 1105−1111.

Kilding R., Akil M., Till S., Amos R., Winfield J., Iles M. M. & Wilson A. G., 2003. A biologically important single nucleotide polymorphism within the toll-like receptor-4 gene is not associated with rheumatoid arthritis. Clin Exp Rheumatol, 21: 340−342.

Li C., Chu N., Wang B., Wang J., Luan J., Han L., Meng D., Wang Y., Suo P., Cheng L., Ma X., Miao Z. & Liu S., 2012. Polymorphisms in the presumptive promoter region of the SLC2A9 gene are associated with gout in a Chinese male population. PloS one, 7: 1−9.

Liu-Bryan R., Scott P., Sydlaske A., Rose D. M. & Terkeltaub R., 2005. Innate immunity conferred by Toll-like receptors 2 and 4 and myeloid differentiation factor 88 expression is pivotal to monosodium urate monohydrate crystal-induced inflammation. Arthritis Rheum, 52: 2936−2946.

Manicassamy S. & Pulendran B., 2009. Modulation of adaptive immunity with Toll-like receptors. Semin Immunol, 21: 185−193.

Martinon F., Petrilli V., Mayor A., Tardivel A. & Tschopp J., 2006. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature, 440: 237−241.

Nguyen H. H., Nguyen T. H., Vu C. D., Nguyen K. T., Le B. V., Nguyen T. L. & Nong V. H., 2012. Novel homozygous p.Y395X mutation in the CYP11B1 gene found in a Vietnamese patient with 11beta-hydroxylase deficiency. Gene, 509: 295−297.

Qing Y. F., Zhou J. G., Zhang Q. B., Wang D. S., Li M., Yang Q. B., Huang C. P., Yin L., Pan S. Y., Xie W. G., Zhang M. Y., Pu M. J. & Zeng M., 2013. Association of TLR4 Gene rs2149356 polymorphism with primary gouty arthritis in a case-control study. PLoS One, 8: 1–9.

Rasheed H., McKinney C., Stamp L.K., Dalbeth N., Topless R. K., Day R., Kannangara D., Williams K., Smith M., Janssen M., Jansen T. L., Joosten L. A., Radstake T. R., Riches P. L., Tausche A. K., Liote F., Lu L., Stahl E. A., Choi H .K., So A. & Merriman T. R., 2016. The Toll-Like Receptor 4 (TLR4) Variant rs2149356 and Risk of Gout in European and Polynesian Sample Sets. PLoS One, 11: 1−8.

VanItallie T. B., 2010. Gout: epitome of painful arthritis. Metabolism, 59 Suppl 1: 32−36.




How to Cite

Xuan, N. T., Ha, L. T., & Chung, D. T. (2021). Association between genotypes of \(\textit{TLR4}\) gene rs2149356 polymorphism and serum level of il-6 in Vietnamese patients with gout. Academia Journal of Biology, 43(2), 11–16.