Skip to main content
Log in

Association of TRPM5 Asn235Ser Polymorphism and Trace Elements/Minerals in Chronic Gastritis Patients: a Case-Control Study

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

The link between chronic gastritis and chemosensory receptors is considered promising for disease prediction and treatment. The transient receptor potential melastatin member channel 5 (TRPM5) is an ion channel and may be a chemosensor in the gastrointestinal tract. Trace elements and minerals involved in many protein structures can change ion channel activity. Our study aimed to determine trace element and mineral levels according to TRPM5 Asn235Ser missense polymorphism distributions in patients with H. pylori (+) and (-) gastritis and to uncover their possible association with disease pathogenesis. In 109 volunteer patients diagnosed with gastritis [64 H. pylori (+), 45 H. pylori (-)], TRPM5 (Asn235Ser) polymorphism was detected by Kompetitive Allele-Specific PCR method (KASP), but no difference was found between the groups. There are differences between the serum trace element (Se, Zn, Cu, Mg, and Cu/Zn) levels of the two groups. High serum Se and Cu/Zn ratios were detected in H. pylori (+) patients. Cu/Zn ratio can be used as a marker of bacterial inflammation. The amount of Se was found to be statistically significant in the serums of H. pylori (+) patients carrying TT and CT genotype, while the amounts of Zn, Cu, and Mg were found as significant of H. pylori (-) patients. The relationship of Se with the H. pylori needs to be investigated further. In addition, H. pylori (+) patients have a significantly higher neutrophils/lymphocytes ratio (NLR) compared to those with H. pylori (-) NLR can be used as an indicator of inflammation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Sipponen P, Maaroos HI (2015) Chronic gastritis. Scand J Gastroenterol 50(6):657–667. https://doi.org/10.3109/00365521.2015.1019918

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Ohata H, Kitauchi S, Yoshimura N, Mugitani K, Iwane M, Nakamura H, Yoshikawa A, Yanaoka K, Arii K, Tamai H, Shimizu Y, Takeshita T, Mohara O, Ichinose M (2004) Progression of chronic atrophic gastritis associated with Helicobacter pylori infection increases risk of gastric cancer. Int J Cancer 109(1):138–143. https://doi.org/10.1002/ijc.11680

    Article  CAS  PubMed  Google Scholar 

  3. Vannarath S, Vilaichone RK, Rasachak B, Mairiang P, Yamaoka Y, Shiota S, Binh TT, Mahachai V (2014) Virulence genes of Helicobacter pylori in gastritis, peptic ulcer and gastric cancer in Laos. Asian Pac J Cancer Prev 15(20):9027–9031. https://doi.org/10.7314/apjcp.2014.15.20.9027

    Article  PubMed  Google Scholar 

  4. Sbarbati A, Bramanti P, Benati D, Merigo F (2010) The diffuse chemosensory system: exploring the iceberg toward the definition of functional roles. Prog Neurobiol 91(1):77–89. https://doi.org/10.1016/j.pneurobio.2010.01.010

    Article  PubMed  Google Scholar 

  5. Depoortere I (2014) Taste receptors of the gut: emerging roles in health and disease. Gut 63(1):179–190. https://doi.org/10.1136/gutjnl-2013-305112

    Article  CAS  PubMed  Google Scholar 

  6. Rasoamanana R, Darcel N, Fromentin G, Tomé D (2012) Nutrient sensing and signalling by the gut. Proc Nutr Soc 71(4):446–455. https://doi.org/10.1017/S0029665112000110

    Article  CAS  PubMed  Google Scholar 

  7. Widmayer P, Küper M, Kramer M, Königsrainer A, Breer H (2012) Altered expression of gustatory-signaling elements in gastric tissue of morbidly obese patients. Int J Obes 36(10):1353–1359. https://doi.org/10.1038/ijo.2011.216

    Article  CAS  Google Scholar 

  8. Kaske S, Krasteva G, König P, Kummer W, Hofmann T, Gudermann T, Chubanov V (2007) TRPM5, a taste-signaling transient receptor potential ion-channel, is a ubiquitous signaling component in chemosensory cells. BMC Neurosci 8:49. https://doi.org/10.1186/1471-2202-8-49

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Yamashita J, Ohmoto M, Yamaguchi T, Matsumoto I, Hirota J (2017) Skn-1a/Pou2f3 functions as a master regulator to generate Trpm5-expressing chemosensory cells in mice. PLoS One 12(12):e0189340. https://doi.org/10.1371/journal.pone.0189340

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Yamaguchi S, Tanimoto A, Iwasa S, Otsuguro K (2019) TRPM4 and TRPM5 channels share crucial amino acid residues for Ca2+ sensitivity but not significance of PI(4,5)P2. Int J Mol Sci 20(8):2012. https://doi.org/10.3390/ijms20082012

    Article  CAS  PubMed Central  Google Scholar 

  11. Oka Y, Butnaru M, von Buchholtz L, Ryba NJ, Zuker CS (2013) High salt recruits aversive taste pathways. Nature 494(7438):472–475

    Article  CAS  Google Scholar 

  12. Resino S, Fernández-Rodríguez A, Pineda-Tenor D, Gómez-Moreno AZ, Sánchez-Ruano JJ, Artaza-Varasa T, Muñoz-Gómez MJ, Virseda-Berdices A, Martín-Vicente M, Martínez I, Jiménez-Sousa MA (2021) TRPM5 rs886277 polymorphism predicts hepatic fibrosis progression in non-cirrhotic HCV-infected patients. J Clin Med 10(3):483. https://doi.org/10.3390/jcm10030483

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Prawitt D, Monteilh-Zoller MK, Brixel L et al (2003) TRPM5 is a transient Ca2+-activated cation channel responding to rapid changes in [Ca2+]i. Proc Natl Acad Sci U S A 100:15166–15171

    Article  CAS  Google Scholar 

  14. Tabur S, Oztuzcu S, Duzen IV, Eraydin A, Eroglu S, Ozkaya M, Demiryürek AT (2015) Role of the transient receptor potential (TRP) channel gene expressions and TRP melastatin (TRPM) channel gene polymorphisms in obesity-related metabolic syndrome. Eur Rev Med Pharmacol Sci 19(8):1388–1397

    CAS  PubMed  Google Scholar 

  15. Oztuzcu S, Onat AM, Pehlivan Y, Alibaz-Oner F, Donmez S, Cetin GY, Yolbas S, Bozgeyik I, Yilmaz N, Ozgen M, Cagatay Y, Kisacik B, Koca SS, Pamuk ON, Sayarlioglu M, Direskeneli H, Demiryurek AT (2015) Association of TRPM channel gene polymorphisms with systemic sclerosis. In Vivo 29(6):763–770

    CAS  PubMed  Google Scholar 

  16. Qu Y, Dang S, Hou P (2013) Gene methylation in gastric cancer. Clin Chim Acta 23(424):53–65. https://doi.org/10.1016/j.cca.2013.05.002

    Article  CAS  Google Scholar 

  17. Ding SZ, Minohara Y, Fan XJ, Wang J, Reyes VE, Patel J, Dirden-Kramer B, Boldogh I, Ernst PB, Crowe SE (2007) Helicobacter pylori infection induces oxidative stress and programmed cell death in human gastric epithelial cells. Infect Immun 75(8):4030–4039. https://doi.org/10.1128/IAI.00172-07

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Dovhanj J, Kljaic K, Vcev A, Ilakovac V (2010) Helicobacter pylori and trace elements. Clin Lab 56(3-4):137–142

    CAS  PubMed  Google Scholar 

  19. Yakoob J, Jafri W, Abid S (2003) Helicobacter pylori infection and micronutrient deficiencies. World J Gastroenterol 9(10):2137–2139. https://doi.org/10.3748/wjg.v9.i10.2137

    Article  PubMed  PubMed Central  Google Scholar 

  20. Millward DJ (2017) Nutrition, infection and stunting: the roles of deficiencies of individual nutrients and foods, and of inflammation, as determinants of reduced linear growth of children. Nutr Res Rev 30(1):50–72. https://doi.org/10.1017/S0954422416000238

    Article  CAS  PubMed  Google Scholar 

  21. Sekine H, Takao K, Yoshinaga K, Kokubun S, Ikeda M (2012) Effects of zinc deficiency and supplementation on gene expression of bitter taste receptors (TAS2Rs) on the tongue in rats. Laryngoscope 122(11):2411–2417. https://doi.org/10.1002/lary.23378

    Article  CAS  PubMed  Google Scholar 

  22. Kojima T, Maeda T, Suzuki A, Yamamori T, Kato Y (2020) Intracellular zinc-dependent TAS2R8 gene expression through CTCF activation. Biomed Res 41(5):217–225. https://doi.org/10.2220/biomedres.41.217

    Article  CAS  PubMed  Google Scholar 

  23. Muhmmed Suliman MA, Bahnacy Juma AA, Ali Almadhani AA, Pathare AV, Alkindi SS, Uwe Werner F (2020) Predictive value of neutrophil to lymphocyte ratio in outcomes of patients with acute coronary syndrome. Arch Med Res 41(8):618–622. https://doi.org/10.1016/j.arcmed.2010.11.006

    Article  Google Scholar 

  24. Ubukata H, Motohashi G, Tabuchi T, Nagata H, Konishi S, Tabuchi T (2010) Evaluations of interferon-γ/interleukin-4 ratio and neutrophil/lymphocyte ratio as prognostic indicators in gastric cancer patients. J Surg Oncol 102(7):742–747. https://doi.org/10.1002/jso.21725

    Article  PubMed  Google Scholar 

  25. Jha HC, Prasad J, Mittal A (2008) High immunoglobulin A seropositivity for combined Chlamydia pneumoniae, Helicobacter pylori infection, and high-sensitivity C-reactive protein in coronary artery disease patients in India can serve as atherosclerotic marker. Heart Vessel 23(6):390–396. https://doi.org/10.1007/s00380-008-1062-9

    Article  Google Scholar 

  26. Farah R, Khamisy-Farah R (2014) Association of neutrophil to lymphocyte ratio with presence and severity of gastritis due to Helicobacter pylori infection. J Clin Lab Anal 28(3):219–223. https://doi.org/10.1002/jcla.21669

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Widmayer P, Breer H, Hass N (2011) Candidate chemosensory cells in the porcine stomach. Histochem Cell Biol 136(1):37–45. https://doi.org/10.1007/s00418-011-0824-0

    Article  CAS  PubMed  Google Scholar 

  28. Ekblad E, Mei Q, Sundler F (2000) Innervation of the gastric mucosa. Microsc Res Tech 48(5):241–257. 

  29. Doihara H, Nozawa K, Kojima R, Kawabata-Shoda E, Yokoyama T, Ito H (2009) QGP-1 cells release 5-HT via TRPA1 activation; a model of human enterochromaffin cells. Mol Cell Biochem 331(1-2):239–245. https://doi.org/10.1007/s11010-009-0165-7

    Article  CAS  PubMed  Google Scholar 

  30. Wu SV, Rozengurt N, Yang M, Young SH, Sinnett-Smith J, Rozengurt E (2002) Expression of bitter taste receptors of the T2R family in the gastrointestinal tract and enteroendocrine STC-1 cells. Proc Natl Acad Sci U S A 99(4):2392–2397. https://doi.org/10.1073/pnas.042617699

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Braun T, Voland P, Kunz L, Prinz C, Gratzl M (2007) Enterochromaffin cells of the human gut: sensors for spices and odorants. Gastroenterology 132(5):1890–1901. https://doi.org/10.1053/j.gastro.2007.02.036

    Article  CAS  PubMed  Google Scholar 

  32. Omran VH, Ranaei M, Neamat N, Shirvani JS, Tilaki KH, Mosapour A, Yamchi MS, Tourani M, Parsian H (2021) Evaluation of serum levels of copper and selenium in Helicobacter pylori positive and negative gastritis patients. J Exp Clin Med 38(2):182–186. https://doi.org/10.52142/omujecm.38.2.23

    Article  Google Scholar 

  33. Montefusco S, Esposito R, D'Andrea L, Monti MC, Dunne C, Dolan B, Tosco A, Marzullo L, Clyne M (2013) Copper promotes TFF1-mediated Helicobacter pylori colonization. PLoS One 8(11):e79455. https://doi.org/10.1371/journal.pone.0079455

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Długaszek M (2019) Studies on relationships between essential and toxic elements in selected body fluids, cells and tissues. Chem Biol Interact 297:57–66. https://doi.org/10.1016/j.cbi.2018.10.011

    Article  CAS  PubMed  Google Scholar 

  35. Lahner E, Persechino S, Annibale B (2012) Micronutrients (other than iron) and Helicobacter pylori infection: a systematic review. Helicobacter. 17(1):1–15. https://doi.org/10.1111/j.1523-5378.2011.00892.x

    Article  CAS  PubMed  Google Scholar 

  36. Ugwuja EI, Akubugwo EI (2009) Impact of maternal Helicobacter pylori infection on trace elements (copper iron and zinc) and pregnancy outcomes. Online J Health Allied Sci 8(4):7

    Google Scholar 

  37. Öztürk N, Kurt N, Özgeriş FB, Baygutalp NK, Tosun MS, Bakan N, Bakan E (2015) Serum zinc, copper, magnesium and selenium levels in children with Helicobacter Pylori infection. Eurasian J Med 47(2):126–129. https://doi.org/10.5152/eurasianjmed.2015.104

    Article  PubMed  PubMed Central  Google Scholar 

  38. Ribeiro SM, Moya AM, Braga CB, Domenici FA, Feitosa MR, Feres O, Rocha JJ, Cunha SF (2016) Copper-Zinc ratio and nutritional status in colorectal cancer patients during the perioperative period. Acta Cir Bras 31(1):24–28. https://doi.org/10.1590/S0102-86502016001300006

    Article  PubMed  Google Scholar 

  39. Takao T, Yanagisawa H, Suka M, Yoshida Y, Onishi Y, Tahara T, Kikuchi T, Kushiyama A, Anai M, Takahashi K, Wakabayashi Sugawa S, Yamazaki H, Kawazu S, Iwamoto Y, Noda M, Kasuga M (2021) Synergistic association of the copper/zinc ratio under inflammatory conditions with diabetic kidney disease in patients with type 2 diabetes: The Asahi Diabetes Complications Study. J Diabetes Investig. https://doi.org/10.1111/jdi.13659

  40. Lu CW, Chang HH, Yang KC, Kuo CS, Lee LT, Huang KC (2016) High serum selenium levels are associated with increased risk for diabetes mellitus independent of central obesity and insulin resistance. BMJ Open Diabetes Res Care 4(1):e000253. https://doi.org/10.1136/bmjdrc-2016-000253

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

Gulsah KOC: Conception and design, genetic analysis, acquisition of data and interpretation, writing and final approval of the manuscript.

Ahu SOYOCAK: Conception and design, genetic analysis, interpretation of data.

Dilek DUZGUN ERGUN: Trace element and mineral measurement, calculation of data

Nural PASTACI OZSOBACI: Trace element and mineral measurement, calculation of data

Serap ANDAC OZTURK: Interpretation of data and writing

Sefa ERGUN: Collection of patient samples, acquisition of data.

All authors participated in the study design, reviewed and revised the manuscript, and approved the final manuscript.

Corresponding author

Correspondence to G. Koc.

Ethics declarations

Ethics Approval and Consent to Participate

The research conforms to the provisions of the Declaration of Helsinki (as revised in Brazil 2013). All participants gave informed consent for the research. The study was approved by Istanbul Aydin University Clinical Trials Ethics Committee (B.30.2.AYD.0.00.00-050.06.04/576).

Consent for Publication

All authors are agree to publish the article.

Conflict of Interest

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Koc, G., Soyocak, A., Duzgun Ergun, D. et al. Association of TRPM5 Asn235Ser Polymorphism and Trace Elements/Minerals in Chronic Gastritis Patients: a Case-Control Study. Biol Trace Elem Res 200, 535–542 (2022). https://doi.org/10.1007/s12011-021-03002-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-021-03002-8

Key words

Navigation