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Published online: 2021-07-12
Submitted: 2021-03-20
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Evaluation of the Frequency of RETN c.62G > A and RETN c.-180C > G Polymorphisms in the Resistin Coding Gene in Girls with Anorexia Nervosa

Karolina Natalia Ziora-Jakutowicz, Janusz Zimowski, Katarzyna Ziora, Małgorzata Bednarska-Makaruk, Elżbieta Świętochowska, Piotr Gorczyca, Maria Szczepańska, Edyta Machura, Małgorzata Stojewska, Katarzyna Gołąb-Jenerał, Małgorzata Blaska, Elżbieta Mizgała-Izworska, Michał Kukla, Filip Rybakowski
DOI: 10.5603/EP.a2021.0065
·
Pubmed: 34292570

open access

Ahead of print
Original Paper
Published online: 2021-07-12
Submitted: 2021-03-20
Accepted: 2021-03-23

Abstract

Introduction: Anorexia nervosa (AN) is a serious psychosomatic syndrome, classified as an eating disorder. AN patients strive to lose weight below normal limits defined for a specific age and height, achieving their goal even at the expense of extreme emaciation. AN has a multifactorial etiology. Genetic factors are believed to be significant in the predisposition to the development of AN. In girls suffering from AN significantly lower levels of resistin (RES) in blood serum are observed as compared to healthy girls. These differences may lead to a thesis that functional genetic polymorphisms in RES coding genes can be responsible for this phenomenon. In our pilot study we demonstrated significant differences in the distribution of genotypes in the loci RETN c.-180C>G of the RES gene in 67 girls with AN and 38 healthy girls. It seems reasonable to compare the frequency of polymorphisms of RETN c.62G>A and RETN c.-180C>G in the RES gene in girls with AN and in healthy subjects in a bigger cohort and to analyse correlations between individual variants of the polymorphisms referred to above and the RES levels in blood plasma. Material and methods: The study covered 308 girls with the restrictive form of AN (AN) and 164 healthy girls (C) (aged 11-19). The RES levels in blood serum were determined by means of the ELISA method on Bio-Vendor, LLC (Asheville, North Carolina, USA). The DNA isolation was carried out by means of Genomic Mini AX BLOOD (SPIN). The PCR reaction was carried out in the thermocycler ThermoCycle T100. 80-150 ng of the studied DNA and relevant starters F and R were added to the reaction mixture. The reaction products were subjected to digestion by restriction enzymes and separated on agarose gels (RFLP). Results: The average RES level in blood serum in the AN group was significantly lower (p< 0.0001) than in the C group. The distribution of genotypes in the loci RETN c.62 of the RES gene was similar in both groups. A significant difference was demonstrated in the distribution of genotypes in the polymorphic site RETN c.-180 of the RES gene between AN and C (p=0.0145) and in the distribution of the C and G alleles in the loci RETN c.-180 (p< 0.0001). The C allele occurred significantly more frequently than the G allele in the C group as compared to the AN group. In all the study subjects jointly (AN and C) a significant positive correlation between the blood RES levels on one hand and the body mass (r= 0.42; p< 0.0001) and BMI (r= 0.61; p< 0.0001) on the other hand was observed. There was no correlation between the concentration of RES in blood serum and the distribution of genotypes in the loci of the resistin gene referred to above. Conclusions: The CG genotype in the loci RETN c.-180 C>G of the RES gene may constitute one of the factors predisposing to the development of AN in girls. The genotype in the loci RETN c.62 G>A and RETN c.-180 C>G of the resistin gene has no influence on the levels of this hormone in blood in AN patients.

Abstract

Introduction: Anorexia nervosa (AN) is a serious psychosomatic syndrome, classified as an eating disorder. AN patients strive to lose weight below normal limits defined for a specific age and height, achieving their goal even at the expense of extreme emaciation. AN has a multifactorial etiology. Genetic factors are believed to be significant in the predisposition to the development of AN. In girls suffering from AN significantly lower levels of resistin (RES) in blood serum are observed as compared to healthy girls. These differences may lead to a thesis that functional genetic polymorphisms in RES coding genes can be responsible for this phenomenon. In our pilot study we demonstrated significant differences in the distribution of genotypes in the loci RETN c.-180C>G of the RES gene in 67 girls with AN and 38 healthy girls. It seems reasonable to compare the frequency of polymorphisms of RETN c.62G>A and RETN c.-180C>G in the RES gene in girls with AN and in healthy subjects in a bigger cohort and to analyse correlations between individual variants of the polymorphisms referred to above and the RES levels in blood plasma. Material and methods: The study covered 308 girls with the restrictive form of AN (AN) and 164 healthy girls (C) (aged 11-19). The RES levels in blood serum were determined by means of the ELISA method on Bio-Vendor, LLC (Asheville, North Carolina, USA). The DNA isolation was carried out by means of Genomic Mini AX BLOOD (SPIN). The PCR reaction was carried out in the thermocycler ThermoCycle T100. 80-150 ng of the studied DNA and relevant starters F and R were added to the reaction mixture. The reaction products were subjected to digestion by restriction enzymes and separated on agarose gels (RFLP). Results: The average RES level in blood serum in the AN group was significantly lower (p< 0.0001) than in the C group. The distribution of genotypes in the loci RETN c.62 of the RES gene was similar in both groups. A significant difference was demonstrated in the distribution of genotypes in the polymorphic site RETN c.-180 of the RES gene between AN and C (p=0.0145) and in the distribution of the C and G alleles in the loci RETN c.-180 (p< 0.0001). The C allele occurred significantly more frequently than the G allele in the C group as compared to the AN group. In all the study subjects jointly (AN and C) a significant positive correlation between the blood RES levels on one hand and the body mass (r= 0.42; p< 0.0001) and BMI (r= 0.61; p< 0.0001) on the other hand was observed. There was no correlation between the concentration of RES in blood serum and the distribution of genotypes in the loci of the resistin gene referred to above. Conclusions: The CG genotype in the loci RETN c.-180 C>G of the RES gene may constitute one of the factors predisposing to the development of AN in girls. The genotype in the loci RETN c.62 G>A and RETN c.-180 C>G of the resistin gene has no influence on the levels of this hormone in blood in AN patients.

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Keywords

anorexia nervosa, polymorphism, resistin

About this article
Title

Evaluation of the Frequency of RETN c.62G>A and RETN c.-180C>G Polymorphisms in the Resistin Coding Gene in Girls with Anorexia Nervosa

Journal

Endokrynologia Polska

Issue

Ahead of print

Article type

Original paper

Published online

2021-07-12

DOI

10.5603/EP.a2021.0065

Pubmed

34292570

Keywords

anorexia nervosa
polymorphism
resistin

Authors

Karolina Natalia Ziora-Jakutowicz
Janusz Zimowski
Katarzyna Ziora
Małgorzata Bednarska-Makaruk
Elżbieta Świętochowska
Piotr Gorczyca
Maria Szczepańska
Edyta Machura
Małgorzata Stojewska
Katarzyna Gołąb-Jenerał
Małgorzata Blaska
Elżbieta Mizgała-Izworska
Michał Kukla
Filip Rybakowski

References (40)
  1. Monteleone P, Castaldo E, Maj M. Neuroendocrine dysregulation of food intake in eating disorders. Regul Pept. 2008; 149(1-3): 39–50.
  2. Starzomska M. Spróbuj tylko nas zawieść. Środowisko rodzinne osób z jadłowstrętem psychicznym i z narcystycznym zaburzeniem osobowości. Fides et Ratio. 2015; 1(21): 231–243.
  3. Pużyński S, Wciórka J. Klasyfikacja zaburzeń psychicznych zaburzeń zachowania w ICD-10. Badawcze kryteria diagnostyczne. Uniwersyteckie Wydawnictwo Medyczne „Vesalius”, Kraków 1998: 106.
  4. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorder (DSM V). APA, Washington DC 2013.
  5. Hsu L. Epidemiology of Eating Disorders. Psychiatr Clin North Am. 1996; 19(4): 681–700.
  6. Rybakowski F. Czynniki genetyczne i cechy osobowości w jadłowstręcie psychicznym. Rozprawa habilitacyjna. Uniwersytet Medyczny im. K. Marcinkowskiego, Poznań 2007.
  7. Baker JH, Schaumberg K, Munn-Chernoff MA. Genetics of Anorexia Nervosa. Curr Psychiatry Rep. 2017; 19(11): 84.
  8. Yilmaz Z, Hardaway JA, Bulik CM. Genetics and Epigenetics of Eating Disorders. Adv Genomics Genet. 2015; 5: 131–150.
  9. Boraska V, Franklin CS, Floyd JAB, et al. Wellcome Trust Case Control Consortium 3. A genome-wide association study of anorexia nervosa. Mol Psychiatry. 2014; 19(10): 1085–1094.
  10. Wang K, Zhang H, Bloss CS, et al. Price Foundation Collaborative Group. A genome-wide association study on common SNPs and rare CNVs in anorexia nervosa. Mol Psychiatry. 2011; 16(9): 949–959.
  11. Hinney A, Scherag S, Hebebrand J. Genetic findings in anorexia and bulimia nervosa. Prog Mol Biol Transl Sci. 2010; 94: 241–270.
  12. Duncan L, Yilmaz Z, Gaspar H, et al. Eating Disorders Working Group of the Psychiatric Genomics Consortium. Significant Locus and Metabolic Genetic Correlations Revealed in Genome-Wide Association Study of Anorexia Nervosa. Am J Psychiatry. 2017; 174(9): 850–858.
  13. Fonseca-Alaniz M, Takada J, Alonso-Vale M, et al. Adipose tissue as an endocrine organ: from theory to practice. J Pediatr (Rio J). 2007; 83(5 Suppl): S192–S203.
  14. Onalan E, Yakar B, Barım AO, et al. Serum apelin and resistin levels in patients with impaired fasting glucose, impaired glucose tolerance, type 2 diabetes, and metabolic syndrome. Endokrynol Pol. 2020; 71(4): 319–324.
  15. Chwalba A, Machura E, Ziora K, et al. The role of adipokines in the pathogenesis and course of selected respiratory diseases. Endokrynol Pol. 2019; 70(6): 504–510.
  16. Patel L, Buckels AC, Kinghorn IJ, et al. Resistin is expressed in human macrophages and directly regulated by PPAR gamma activators. Biochem Biophys Res Commun. 2003; 300(2): 472–476.
  17. Kunnari A, Ukkola O, Päivänsalo M, et al. High plasma resistin level is associated with enhanced highly sensitive C-reactive protein and leukocytes. J Clin Endocrinol Metab. 2006; 91(7): 2755–2760.
  18. Trayhurn P, Beattie JH. Psychological role of adipose tissue: white adipose tissue as an endocrine and secretory organ. Proc Nurt Soc. 2006; 51: 111–114.
  19. Kim KH, Lee K, Moon YS, et al. A cysteine-rich adipose tissue-specific secretory factor inhibits adipocyte differentiation. J Biol Chem. 2001; 276(14): 11252–11256.
  20. Smith SR, Bai F, Charbonneau C, et al. A Promoter Genotype and Oxidative Stress Potentially Link Resistin to Human Insulin Resistance. Diabetes. 2003; 52(7): 1611–1618.
  21. Tyszkiewicz-Nwafor M, Rybakowski F, Dmitrzak-Weglarz M, et al. Brain-Derived Neurotrophic Factor and Oxytocin Signaling in Association With Clinical Symptoms in Adolescent Inpatients With Anorexia Nervosa-A Longitudinal Study. Front Psychiatry. 2019; 10: 1032.
  22. Steppan CM, Lazar MA. Resistin and obesity-associated insulin resistance. Trends Endocrinol Metab. 2002; 13(1): 18–23.
  23. Kim KH, Lee K, Moon YS, et al. A cysteine-rich adipose tissue-specific secretory factor inhibits adipocyte differentiation. J Biol Chem. 2001; 276(14): 11252–11256.
  24. Ziora K, Oświęcimska J, Świętochowska E, et al. Assesment of serum levels resistin in girls with anorexia nervosa. Part I. Relationship between resistin and body mass index. Neuroendocrinol Lett. 2011; 32(5): 101–106.
  25. Křížová J, Dolinková M, Lacinová Z, et al. Adiponectin and resistin gene polymorphisms in patients with anorexia nervosa and obesity and its influence on metabolic phenotype. Physiol Res. 2008; 57(4): 539–546.
  26. Ziora-Jakutowicz K, Zimowski J, Ziora KT, et al. Genetic polymorphisms and serum concentrations of adiponectin and resistin in anorexia nervosa and healthy controls - pilot study. Neuro Endocrinol Lett. 2017; 38(3): 215–223.
  27. Engert JC, Vohl MC, Williams SM, et al. 5' flanking variants of resistin are associated with obesity. Diabetes. 2002; 51(5): 1629–1634.
  28. Pizzuti A, Argiolas A, Di Paola R, et al. An ATG repeat in the 3'-untranslated region of the human resistin gene is associated with a decreased risk of insulin resistance. J Clin Endocrinol Metab. 2002; 87(9): 4403–4406.
  29. Ma X, Warram JH, Trischitta V, et al. Genetic variants at the resistin locus and risk of type 2 diabetes in Caucasians. J Clin Endocrinol Metab. 2002; 87(9): 4407–4410.
  30. Tan MS, Chang SY, Chang DM, et al. Association of resistin gene 3'-untranslated region +62G-->A polymorphism with type 2 diabetes and hypertension in a Chinese population. J Clin Endocrinol Metab. 2003; 88(3): 1258–1263.
  31. Gouni-Berthold I, Giannakidou E, Faust M, et al. Resistin gene 3'-untranslated region +62G-->A polymorphism is associated with hypertension but not diabetes mellitus type 2 in a German population. J Intern Med. 2005; 258(6): 518–526.
  32. Yannakoulia M, Yiannakouris N, Blüher S, et al. Body fat mass and macronutrient intake in relation to circulating soluble leptin receptor, free leptin index, adiponectin, and resistin concentrations in healthy humans. J Clin Endocrinol Metab. 2003; 88(4): 1730–1736.
  33. Dolezalova R, Lacinova Z, Dolinkova M, et al. Changes of endocrine function of adipose tissue in anorexia nervosa: comparison of circulating levels versus subcutaneous mRNA expression. Clin Endocrinol (Oxf). 2007; 67(5): 674–678.
  34. Housova J, Anderlova K, Krizová J, et al. Serum adiponectin and resistin concentrations in patients with restrictive and binge/purge form of anorexia nervosa and bulimia nervosa. J Clin Endocrinol Metab. 2005; 90(3): 1366–1370.
  35. Ziora K, Oświęcimska J, Świętochowska E, et al. Assesment of serum levels resitin in girls with anorexia nervosa. Part II. Relationship between serum levels of resistin and thyroid, adrenal and gonadal hormones. Neuroendocrinol Lett. 2011; 32(2): 101–108.
  36. Brichard SM, Delporte ML, Lambert M. Adipocytokines in anorexia nervosa: a review focusing on leptin and adiponectin. Horm Metab Res. 2003; 35(6): 337–342.
  37. Dostalova I, Kunesova M, Duskova J, et al. Adipose tissue resistin levels in patients with anorexia nervosa. Nutrition. 2006; 22(10): 977–983.
  38. Lehrke M, Reilly MP, Millington SC, et al. An inflammatory cascade leading to hyperresistinemia in humans. PLoS Med. 2004; 1(2): e45.
  39. Koerner A, Kratzsch J, Kiess W. Adipocytokines: leptin — the classical, resistin — the controversical, adiponectin — the promising, and more to come. Best Pract Res Clin Endocrinol Metab. 2005; 19(4): 525–546.
  40. Rea R, Donnelly R. Resistin: an adipocyte-derived hormone. Has it a role in diabetes and obesity? Diabetes Obes Metab. 2004; 6(3): 163–170.

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