Genetic polymorphisms namely TLR2 Gene Arg753gln and Arg677trp polymorphisms and tuberculosis: Comparison on the effects of molecular weight alterations

Pathum Sookaromdee; Viroj Wiwanitkit; Beuy Joob

doi:10.4103/bbrj.bbrj_19_19

ORIGINAL ARTICLE

Year : 2019 | Volume : 3 | Issue : 2 | Page : 129-130

Genetic polymorphisms namely TLR2 Gene Arg753gln and Arg677trp polymorphisms and tuberculosis: Comparison on the effects of molecular weight alterations

Pathum Sookaromdee¹, Viroj Wiwanitkit², Beuy Joob³
¹ TWS Medical Center, Bangkok, Thailand
² Department of Biological Science, Ayobabalola University, Ikeji-Arakeji, Osun State, Nigeria
³ Medical Center, Medical Academic Center, Bangkok, Thailand

Date of Submission	15-Jan-2019
Date of Decision	17-Feb-2019
Date of Acceptance	30-Mar-2019
Date of Web Publication	17-Jun-2019

Correspondence Address:
Dr. Pathum Sookaromdee
TWS Medical Center, Bangko
Thailand

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/bbrj.bbrj_19_19

Abstract

Background: Tuberculosis is an important mycobacterial infection. This problem is still the present public health problem in several countries around the world. The genetic underlying factor is usually mentioned for the effect on the natural history of tuberculosis infection. Methods: Here, the authors perform a standard assessment on the molecular change due to TLR2 gene Arg753Gln and Arg677Trp polymorphisms and further study on the effect on the corresponding phenotypic expression changes. Results: The molecular weight changes comparing to naïve molecule in cases of Arg753Gln and Arg677Trp polymorphisms are equal to –16.1% and +17.2%, respectively. Conclusion: According to the molecular structure analysis, Arg753Gln has a relationship with active tuberculosis whereas Arg677Trp polymorphism is not.

Keywords: Effect, genetic, polymorphism, tuberculosis

How to cite this article:
Sookaromdee P, Wiwanitkit V, Joob B. Genetic polymorphisms namely TLR2 Gene Arg753gln and Arg677trp polymorphisms and tuberculosis: Comparison on the effects of molecular weight alterations. Biomed Biotechnol Res J 2019;3:129-30

How to cite this URL:
Sookaromdee P, Wiwanitkit V, Joob B. Genetic polymorphisms namely TLR2 Gene Arg753gln and Arg677trp polymorphisms and tuberculosis: Comparison on the effects of molecular weight alterations. Biomed Biotechnol Res J [serial online] 2019 [cited 2019 Jul 20];3:129-30. Available from: http://www.bmbtrj.org/text.asp?2019/3/2/129/260476

Introduction

The effect of genetic underlying factor on the natural history of medical disorder is interesting. For tuberculosis, an important mycobacterial infection, the effect of genetic background is well mentioned in clinical literature.^[1],[2] The role of human genetic variability in tuberculosis might be observable in several ways such as disease susceptibility, disease progression, and response to pharmacological treatment.^[1],[2],[3] Of several genetic polymorphisms, toll-like receptor 2 (TLR2 gene) polymorphism is an important genetic polymorphism that is mentioned for its interrelationship with a natural history of tuberculosis.^[1],[2] TLR2 gene is an important gene with specific function for pattern recognition which is necessary for recognizing and defense-invading microorganisms. The important genetic polymorphisms which are documented for the clinical relationships with tuberculosis are Arg753Gln and Arg677Trp polymorphisms. Here, the authors perform a standard assessment on the molecular change due to TLR2 gene Arg753Gln and Arg677Trp polymorphisms and further study on the effect on the corresponding phenotypic expression changes.

Methods

This study is aimed at assessment of the molecular structure change in the genetic polymorphism, namely TLR2 gene Arg753Gln and Arg677Trp polymorphisms. The genetic effect on the natural history of tuberculosis is mentioned in the literature. For assessment, the authors performed the standard quantum molecular analysis according to the previous publications in other medical problems^{[4],[5],[6],[7]} to assess the molecular weight change in the naïve and polymorphisms. The comparison of the derived molecular weight at the focused mutation positions, 753 and 667, was done. Further simulation on the phenotypic expression of both naïve and mutated cases was done and compared. This is a bioinformatics modelling study and does not involve any human or animal subjects or clincial specicmen, therefore, it requires no ethical approval or written informed consent.

Results

According to the analysis, the molecular weights at the focused site 753 and 667 are equal to 174 Da and 174 Da, respectively. In mutated types, the molecular weights at site 753 for Arg753Gln and at site 677 for Arg677Trp polymorphisms are equal to 146 Da and 204 Da, respectively. The molecular weight changes comparing to naïve molecule in cases of Arg753Gln and Arg677Trp polymorphisms are equal to −28 Da (−16.1%) and +30 Da (+17.2%), respectively.

According to the simulation, per same one TLR2 molecule, the required number of molecule for completeness of phenotypic expression for Arg753Gln and Arg677Trp polymorphisms, giving primary assumption that the requirement for naïve case is 1, will be predicted as 0.839 and 1.172 molecules, respectively.

Discussion

Effect of the genetic polymorphism on the manifestation of tuberculosis infection is interesting and widely studied at present.^[1] TLR2 is an important molecular receptor that belongs to innate immunity that is important in the pathogenesis process of infections including tuberculosis.^[8],[9] The active pulmonary tuberculosis expression and relationship with Arg753Gln and Arg677Trp polymorphisms are reported in the literature.^[10] Soeroto et al. found that “Arg753Gln polymorphism of TLR2 gene is a risk factor for active pulmonary TB while Arg677Trp polymorphism is not.^[10]” The clinical interrelationship with active tuberculosis and extrapulmonary tuberculosis of TLR2 Arg753Gln, but not Arg677T, is also reported in another publication by Saleh et al.^[11]

In our present study, a similar finding can be observed. According to the molecular weight change analysis and further simulation study on the effect on phenotypic change, it can show that the Arg753Gln polymorphism of TLR2 gene results in easier completeness of final phenotype manifestation due to the requirement of less substrate. According to the present study, it can show that Arg753Gln has a relationship with active tuberculosis whereas Arg677Trp polymorphism is not.

Conclusion

According to the molecular structure analysis, Arg753Gln has a relationship with active tuberculosis whereas Arg677Trp polymorphism is not.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	van Tong H, Velavan TP, Thye T, Meyer CG. Human genetic factors in tuberculosis: An update. Trop Med Int Health 2017;22:1063-71.
2.	Harishankar M, Selvaraj P, Bethunaickan R. Influence of genetic polymorphism towards pulmonary tuberculosis susceptibility. Front Med (Lausanne) 2018;5:213.
3.	Woodman M, Haeusler IL, Grandjean L. Tuberculosis genetic epidemiology: A Latin American Perspective. Genes (Basel) 2019;10:pii: E53. doi: 10.3390/genes10010053.
4.	Yasri S, Wiwanitkit V. Caspase recruitment domain-containing protein 8 rs2043211 polymorphism and cardiovascular disease susceptibility. Anatol J Cardiol 2018;20:368.
5.	Joob B, Wiwanitkit V. Interleukin-2-330T/G and interleukin-10-1082A/G genetic polymorphisms and B-cell non-Hodgkin lymphoma Turk J Haematol 2018;35:301-2.
6.	Joob B, Wiwanitkit V. Genetic polymorphism on susceptibility to nephrotoxic properties of BTEXs compounds. J Occup Environ Med 2018;60:e559.
7.	Srriwijitalai W, Wiwanitkit V. Interleukin-6 -174G/C polymorphism and end-stage renal disease: Is there any role? Saudi J Kidney Dis Transpl 2018;29:747-8. [PUBMED] [Full text]
8.	Caplan IF, Maguire-Zeiss KA. Toll-like receptor 2 signaling and current approaches for therapeutic modulation in synucleinopathies. Front Pharmacol 2018;9:417.
9.	Gopalakrishnan A, Salgame P. Toll-like receptor 2 in host defense against Mycobacterium tuberculosis: To be or not to be-that is the question. Curr Opin Immunol 2016;42:76-82.
10.	Soeroto AY, Dahlan Z, Kartasasmita CB, Parwati I. Association between arg753Gln and arg677Trp polymorphisms of TLR2 gene with active pulmonary tuberculosis in an Indonesian population. Acta Med Indones 2018;50:53-60.
11.	Saleh MA, Ramadan MM, Arram EO. Toll-like receptor-2 arg753Gln and arg677Trp polymorphisms and susceptibility to pulmonary and peritoneal tuberculosis. APMIS 2017;125:558-64.