Clinical features of gastroesophageal reflux disease in children with different genotypes of C825T polymorphic loci of GNB3 gene

Marta Dats-Opoka; Halyna Makukh

doi:10.20883/jms.2017.248

Authors

Marta Dats-Opoka Danylo Halytsky Lviv National Medical University
Halyna Makukh State Institution "Institute of Hereditary Pathology Ukrainian National Academy of Medical Sciences", Ukraine

DOI:

https://doi.org/10.20883/jms.2017.248

Keywords:

gastroesophageal reflux disease, children, physical development, polymorphism ?825?, GNB3

Abstract

Introduction. Considering the steady growth of the gastroesophageal reflux disease (GERD) in children in recent decades, the difficulty of GERD diagnosing in children, the variety of GERD clinical and morphological features as well as the factors that cause it, including genetic predisposition, a detailed analysis of each of them remains relevant.
Aim. To analyze the peculiarities of nutritional status in children with GERD and its correlation with the different genotypes of C825T polymorphic loci of GNB3 gene as well as its association with different GERD clinical manifestations.
Material and Methods. The analysis of GERD clinical features was carried out and the nutritional status in 100 children of school age was estimated. Molecular and genetic research of C825T loci of GNB3 gene using PCR method (rs5443) was carried out in the studied group (100 children) and in 40 healthy children that formed the control group.
Results. The distribution of the genotypes of C825T polymorphic loci of the GNB3 gene in children with GERD and healthy children in the control group did not have any statistically significant difference (?2 = 0.27, ? = 0.87). Among more than a half of the children in both groups, the GNB3 825ST heterozygous genotype were detected (54.0% of the experimental group and 57.5% of the control group), according to de Vries et al. data is a factor of GERD increased risk. The association between the genotype of C825T locus of GNB3 gene and the data of intragastric endoscopy with pH monitoring was found: in patients with hyperacidic GERD the genotype 825CT was predominantly revealed, and in children with normal and hypoacidic GERD a higher frequency of the 825TT genotype was found. In children with GERD having a lack of the nutritional status (61%), the genotype 825CT (61.82%, p = 0.013) and 825TT (100%, p = 0.005) of the GNB3 gene were detected significantly more often.
Conclusions. The distribution of the genotypes of C825T polymorphic loci of the GNB3 gene in children with GERD was determined. Differences in GERD development depending on the different GNB3 genotypes were not detected. The distribution of the genotypes of C825T loci of the GNB3 gene remained unchanged at different GERD clinical manifestations. The presence of 825CT and 825TT genotypes of GNB3 gene in patients with GERD is associated with a decrease in physical development signs. The association between genotype of C825T loci of GNB3 gene and pH intragastric endoscopy data was identified: in patients with hyperacidity GERD 825CC genotype was usually found, and in children with normal- and hypoacidity GERD 825TT genotype was usually found.

Downloads

Download data is not yet available.

References

Holtmann G, Adam B, Liebregts T. Review article: the patient with gastro-oesophageal reflux disease—lifestyle advice and medication. Aliment Pharmacol Ther. 2004;20(Suppl 8):24–7.

Terry P, Lagergren J, Wolk A, Nyren O. Reflux-inducing dietary factors and risk of adenocarcinoma of the esophagus and gastric cardia. Nutr Cancer. 2000;38:186–91.

Chourasia D, Ghoshal UC. Pathogenesis of gastro-oesophageal reflux disease: what role do Helicobacter pylori and host genetic factors play? Trop Gastroenterol. 2008;29:13–9.

Ghoshal UC, Chourasia D. Gastroesophageal reflux disease and Helicobacter pylori: what may be the relationship? J Neurogastroenterol Motil. 2010;16:243–50.

Rohof WO, Hirsch DP, Boeckxstaens GE. Pathophysiology and management of gastroesophageal reflux disease. Minerva Gastroenterol Dietol. 2009;55:289–300.

Boeckxstaens GE. Review article: the pathophysiology of gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2007;26:149–60.

Cameron AJ, Lagergren J, Henriksson C, Nyren O, Locke GR 3rd, Pedersen NL. Gastroesophageal reflux disease in monozygotic and dizygotic twins. Gastroenterology. 2002;122:55–9.

Mohammed I, Cherkas LF, Riley SA, Spector TD, Trudgill NJ. Genetic influences in gastro-oesophageal reflux disease: a twin study. Gut. 2003;52:1085–9.

Lembo A, Zaman M, Jones M, Talley NJ. Influence of genetics on irritable bowel syndrome, gastro-oesophageal reflux and dyspepsia: a twin study. Aliment Pharmacol Ther. 2007;25:1343–50.

Uday C. Ghoshal & Dipti Chourasia Genetic factors in the pathogenesis of gastroesophageal reflux disease Indian J Gastroenterol. 2011;30(2):55–62. DOI: 10.1007/s12664-011-0095-7.

Heidi E. Hamm The Many Faces of G Protein Signaling The Journal of Biological Chemistry. 1998 January 9;273:669–672. DOI: 10.1074/jbc.273.2.669.

Siffert W, Rosskopf D, Siffert G et al. Association of a human G-protein beta3 subunit variant with hypertension. Nat Genet. 1998;18:45–8.

Rosskopf D, Manthey I, Habich Cet al. Identification and characterization of G beta 3s2, a novel splice variant of the G-protein beta 3 subunit. Biochem J. 2003 Apr 1;371:223–32. DOI: 10.1042/bj20021208.

Virchow S, Ansorge N, Ru¨ bben H, Siffert G, and Siffert W. Enhanced fMLP-stimulated chemotaxis in human neutrophils from individuals carrying the G protein 3 subunit 825 T-allele. FEBS Lett. 1998;436:155–158.

Lindemann M, Virchow S, Ramann F, Barsegian V, Kreuzfelder E, Siffert W, Müller N, and Grosse-Wilde H. The G protein ß3 subunit 825T allele is a genetic marker for enhanced T cell response. FEBS Lett. 2001;495:82–86.

de Vries DR, ter Linde JJ, van Herwaarden MA, Smout AJ, Samsom M. Gastroesophageal reflux disease is associated with the C825T polymorphism in the G-protein beta3 subunit gene (GNB3). Am J Gastroenterol. 2009;104:281–5.

Lee HJ, Cha JH, Ham BJ et al. Association between a G-protein ß3 sub-unit gene polymorphism and the symptomatology and treatment responses of major depressive disorders. Pharmacogenomics J. 2004;4:29–33.

Siffert W, Forster P, Jöckel KH et al.Worldwide ethnic distribution of the G protein beta3 subunit 825T allele and its association with obesity in Caucasian, Chinese, and Black African individuals. J Am Soc Nephrol. 1999 Sep;10:1921–30.

Hauner H, Meier M, Jöckel KH, Frey UH, Siffert W. Prediction of successful weight reduction under sibutramine therapy through genotyping of the G-protein beta3 subunit gene (GNB3) C825T polymorphism. Pharmacogenetics. 2003 Aug;13(8):453-9.

Park YM, Chung YC, Lee SH et al. G-protein b3 subunit gene 825C/T polymorphism is not associated with olanzapine-induced weight gain in Korean schizophrenic patients. Psychiatry Investig. 2009;6:39–43.

Rosskopf D, Manthey I, Siffert W. Identification and ethnic distribution of major haplotypes in the gene GNB3 encoding the G-protein beta3 subunit. Pharmacogenetics. 2002;12:209–20.

Tahara T, Arisawa T, Shibata T et al. Homozygous 825T allele of the GNB3 protein influences the susceptibility of Japanese to dyspepsia. Dig Dis Sci. 2008;53:642–6.

Holtmann G, Siffert W, Haag S et al. G-protein b3 subunit 825 CC genotype is associated with unexplained (functional) dyspepsia. Gastroenterology. 2004;126:971–9.

Lee H-j, Lee S-y, Choi JE, Kim JH, Sung I-k, Park HS, Jin CJ. G protein ß3 subunit, interleukin-10, and tumor necrosis factor-? gene polymorphisms in Koreans with irritable bowel syndrome. Neurogastroenterology & Motility. 2010;22:758–763. DOI: 10.1111/j.1365-2982.2010.01496.x

Oshima T, Nakajima S, Yokoyama T, Toyoshima F, Sakurai J, Tanaka J, Tomita T, Kim Y, Hori K, Matsumoto T, Miwa H. The G-Protein ß3 subunit 825 TT genotype is associated with epigastric pain syndrome-like dyspepsia. BMC Med Genet. 2010;11:13. DOI: 10.1186/1471-2350-11-13.

Gutersohn A, Naber C, Müller N, Erbel R, and Siffert W. G protein ß3 subunit 825 TT genotype and post-pregnancy weight retention. Lancet. 2000;355:1240–1241.

Hengstenberg C, Schunkert H, Mayer B, Döring A, Löwel H, Hense H, Fischer M, Riegger GA, and Holmer SR. Association between a polymorphism in the G protein ß3 subunit gene (GNB3) with arterial hypertension but not with myocardial infarction. Cardiovasc Res. 2001;49:820–827.

Winfried Siffert Effects of the G protein ß3-subunit gene C825T polymorphism: should hypotheses regarding the molecular mechanisms underlying enhanced G protein activation be revised? Focus on “A splice variant of the G protein ß3-subunit implicated in disease states does not modulate ion channels”. Physiological Genomics. 2003;2(13):81–84 DOI: 10.1152/physiolgenomics.00031.2003.

Ruiz-Velasco V and Ikeda SR. A splice variant of the G protein ß3-subunit implicated in disease states does not modulate ion channels. Physiol Genomics. 2003;13:85–95.