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Grelin ve Grelin Reseptörü Polimorfizmlerinin Tip 2 Diyabetle İlişkisi

Yıl 2022, Cilt: 13 Sayı: 2, 218 - 227, 31.08.2022
https://doi.org/10.22312/sdusbed.1115667

Öz

Bir gastrik peptit olan grelin ve onun büyüme hormonu salgılatıcı G protein-bağlı reseptörünün glukoz metabolizması ve enerji homeostazında önemli bir rol oynadığına dair ciddi kanıtlar mevcuttur. Bu nedenle, Tip 2 diyabet için duyarlılık alelleri taşıyan bu genler potansiyel birer aday olarak değerlendirilmektedir.
Isparta yöresinden 75 Tip 2 diyabet hastası ve 25 kontrolden oluşan 100 Türk yetişkin bireyin dahil edildiği vaka-kontrol kesitsel ilişkilendirme çalışması yapıldı. Grelin geninde dört promotör (rs26311, rs26312, rs27647, rs3755777) ve bir intronik (rs35683) bölge ve Grelin reseptöründe bir intronik (rs509035) ve bir 3'UTR (rs565105) bölge tek nükleotid polimorfizmleri seçilerek Tip 2 diyabet ile ilişkisi Matris Destekli Lazer Desorpsiyon/İyonizasyon Uçuş Süresi Kütle Spektrometresi sistemi kullanılarak araştırıldı.
Tip 2 diyabet ile iki adet tek nükleotid polimorfizmi arasında anlamlı bir ilişki saptandı: Grelin geninin promotör bölgesinde yer alan rs27647 ve intron 1'de bulunan rs35683 (P<0.05).
Sonuç olarak, elde edilen bulgular Isparta yöresinde yaşayan Tip 2 diyabet toplumunda grelin polimorfizmlerinin hastalık gelişimine yatkınlık oluşturabileceğini düşündürmektedir.

Destekleyen Kurum

Süleyman Demirel Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimi

Proje Numarası

4311-GÜP-15

Teşekkür

Süleyman Demirel Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimi tarafından 4311-GÜP-15 proje numarası ile desteklenmiştir.

Kaynakça

  • [1] International Diabetes Federation 2019. IDF Diabetes Atlas, 9th ed.; International Diabetes Federation: Brussels, Belgium.
  • [2] World Health Organization 2021. Diabetes. Available online: https://www.who.int/news-room/fact-sheets/detail/diabetes (accessed on 5 December 2021).
  • [3] American Diabetes Association 2014. Diagnosis and classification of diabetes mellitus. Diabetes Care 37, S81–S90.
  • [4] Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus 2003. Diabetes Care 26, S5–S20.
  • [5] Loktionov A 2003. Common gene polymorphisms and nutrition: emerging links with pathogenesis of multifactorial chronic diseases. J Nutr Biochem. 14(8):426–51.
  • [6] Kido, Y. 2017. Gene–environment interaction in type 2 diabetes. Diabetology international, 8(1), 7-13.
  • [7] Willemsen G, Ward KJ, Bell CG, Christensen K, Bowden J, Dalgard C, Harris JR, Kaprio J, Lyle R, Magnusson PK, Mather KA, Ordonana JR, Perez-Riquelme F, Pedersen NL, Pietilainen KH, Sachdev PS, Boomsma DI, Spector T 2015: The concordance and heritability of type 2 diabetes in 34,166 twin pairs from international twin registers: the Discordant Twin (DISCOTWIN) Consortium. Twin Res Hum Genet 18:762–771.
  • [8] Costa V, Casamassimi A, Ciccodicola A 2010. Nutritional genomics era: opportunities toward a genome-tailored nutritional regimen. J Nutr Biochem. 21(6):457–67.
  • [9] Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, et al. 1999 Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 656–660.
  • [10] Tolle V, Zizzari P, Tomasetto C, Rio MC, Epelbaum J, et al. 2001 In vivo and in vitro effects of ghrelin/motilin-related peptide on growth hormone secretion in the rat. Neuroendocrinology 54–61.
  • [11] Yang J, Brown MS, Liang G, Grishin NV, Goldstein JL 2008. Identification of the Acyltransferase that Octanoylates Ghrelin, an Appetite-Stimulating Peptide Hormone. Cell 387–396.
  • [12] Hassouna R, Zizzari P, Tolle V, 2010. The ghrelin/obestatin balance in the physiological and pathological control of GH secretion, body composition and food intake. Journal of Neuroendocrinology 794–804.
  • [13] Baessler, A., Hasinoff, M., Fischer, M. 2005. Genetic linkage and association of the growth hormone secretagogue receptor (ghrelin receptor) gene in human obesity. Diabetes. 54:259–67.
  • [14] Baessler, A, Fisher, M, Mayer, B. 2007. Epistatic interaction between haplotypes of the ghrelin ligand and receptor genes influence susceptibility to myocardial infarction and coronary artery disease. Human Molec Genet. 16:887–99.
  • [15] Zavarella, S., Petrone, A., Zampetti, S. 2008. A new variation in the promoter region, the −604 C>T and the Leu72Met polymorphism of the ghrelin gene are associated with the protection to insulin resistance. Int J Obes. 32:663–8.
  • [16] Gueorguiev, M., Lecoeur, C., Meyre, D., Benzinou, M., Mein, C. A., Hinney, A., Froguel, P. 2009. Association studies on ghrelin and ghrelin receptor gene polymorphisms with obesity. Obesity, 17(4), 745-754.
  • [17] Liu, B., Garcia, E. A., & Korbonits, M. 2011. Genetic studies on the ghrelin, growth hormone secretagogue receptor (GHSR) and ghrelin O-acyl transferase (GOAT) genes. Peptides, 32(11), 2191-2207.
  • [18] Alberti, K. G. M. M., & Zimmet, P. Z., 1998. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus. Provisional report of a WHO consultation. Diabetic medicine,15(7), 539-553.
  • [19] Gueorguiev M, Korbonits M, 2013. Genetics of the ghrelin system. Endocr Dev. Basel, Karger, 25, 25–40 (DOI: 10.1159/000348665).
  • [20] Joatar F, et al. 2017. Leu72Met and other ıntronic polymorphisms in the GHRLand GHSR genes are not associated with type 2 diabetes mellitus, ınsulin resistance, or serum ghrelin levels in a saudi population. Endocrinol Metab 32:360-369.
  • [21] Wang Y, et al. 2010. Ghrelin inhibits insulin secretion through the AMPK–UCP2 pathway in b cells. Federation of European Biochemical Societies Letters 201; 584, 1503–1508.
  • [22] Elabadlah H, Hameed R, D’Souza C, Mohsin S, Adeghate E, 2020. Exogenous ghrelin ıncreases plasma ınsulin level in diabetic rats. Biomolecules, 10, 633; doi:10.3390/biom10040633.
  • [23] Pulkkinen L, Ukkola O, Kolehmainen M, Uusitupa M, 2010. Ghrelin in diabetes and metabolic syndrome. International Journal of Peptides Volume Article ID 248948, 11 pages doi:10.1155/2010/248948.
  • [24] Chorley, B. N., Wang, X., Campbell, M. R., Pittman, G. S., Noureddine, M. A., & Bell, D. A. 2008. Discovery and verification of functional single nucleotide polymorphisms in regulatory genomic regions: current and developing technologies. Mutation Research/Reviews in Mutation Research, 659(1-2), 147-157.
  • [25] Choi HJ, et al. 2015. Polymorphisms in the ghrelin gene are associated with serum high-density lipoprotein cholesterol level and not with type 2 diabetes mellitus in koreans. The Journal of Clinical Endocrinology & Metabolism 91(11):4657– 4663.
  • [26] Mora M, Adam V, Palomera E, Blesa S, Díaz G, Buquet X, et al. 2015 Ghrelin Gene Variants Influence on Metabolic Syndrome Components in Aged Spanish Population. PLoS ONE 10(9): e0136931. doi:10.1371/journal.pone.0136931.
  • [27] Li P, et al. 2014. Genetic association analysis of 30 genes related to obesity in a european american population. Int J Obes (Lond). 38(5): 724–729. doi:10.1038/ijo.2013.140.
  • [28] Chung W, et al. 2009. Analysis of 30 genes (355 snps) related to energy homeostasis for association with adiposity in european-american and yup’ik eskimo populations. Hum Hered 67:193–205.
  • [29] Mager U, Degenhardt T, Pulkkinen L, Kolehmainen M, Tolppanen A-M, et al. 2008. Variations in the Ghrelin Receptor Gene Associate with Obesity and Glucose Metabolism in Individuals with Impaired Glucose Tolerance. PLoS ONE 3(8): e2941. doi:10.1371/journal.pone.0002941.
  • [30] Luglio HF, Inggriyani CG, Huriyat E, Julia M, Susilowat R, 2014. Int J Mol Epidemiol Genet 5(4):195-19.

Relationship of Ghrelin and Ghrelin Receptor Polymorphisms with Type 2 Diabetes

Yıl 2022, Cilt: 13 Sayı: 2, 218 - 227, 31.08.2022
https://doi.org/10.22312/sdusbed.1115667

Öz

There is compelling evidence that the gastric peptide ghrelin and its growth hormone secretagogue G protein-coupled receptor play an important role in glucose metabolism and energy homeostasis. Therefore, these genes carrying susceptibility alleles for Type 2 diabetes are considered as potential candidates.

A case-control cross-sectional association study was conducted in Isparta region, including 75 Type 2 diabetes patients and 100 Turkish adult individuals, including 25 controls. Four promoters (rs26311, rs26312, rs27647, rs3755777) and an intronic (rs35683) region in the ghrelin gene and an intronic (rs509035) and a 3'UTR (rs565105) region in the ghrelin receptor are associated with type 2 diabetes by selecting single nucleotide polymorphisms Matrix Assisted Laser Desorption /Ionization was investigated using the Time of Flight Mass Spectrometer system.

A significant relationship was found between type 2 diabetes and two single-nucleotide polymorphisms: rs27647 in the promoter region of the ghrelin gene and rs35683 in intron 1 (P<0.05).
In conclusion, the findings suggest that ghrelin polymorphisms may predispose to disease development in the Type 2 diabetes population living in the Isparta region.

Proje Numarası

4311-GÜP-15

Kaynakça

  • [1] International Diabetes Federation 2019. IDF Diabetes Atlas, 9th ed.; International Diabetes Federation: Brussels, Belgium.
  • [2] World Health Organization 2021. Diabetes. Available online: https://www.who.int/news-room/fact-sheets/detail/diabetes (accessed on 5 December 2021).
  • [3] American Diabetes Association 2014. Diagnosis and classification of diabetes mellitus. Diabetes Care 37, S81–S90.
  • [4] Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus 2003. Diabetes Care 26, S5–S20.
  • [5] Loktionov A 2003. Common gene polymorphisms and nutrition: emerging links with pathogenesis of multifactorial chronic diseases. J Nutr Biochem. 14(8):426–51.
  • [6] Kido, Y. 2017. Gene–environment interaction in type 2 diabetes. Diabetology international, 8(1), 7-13.
  • [7] Willemsen G, Ward KJ, Bell CG, Christensen K, Bowden J, Dalgard C, Harris JR, Kaprio J, Lyle R, Magnusson PK, Mather KA, Ordonana JR, Perez-Riquelme F, Pedersen NL, Pietilainen KH, Sachdev PS, Boomsma DI, Spector T 2015: The concordance and heritability of type 2 diabetes in 34,166 twin pairs from international twin registers: the Discordant Twin (DISCOTWIN) Consortium. Twin Res Hum Genet 18:762–771.
  • [8] Costa V, Casamassimi A, Ciccodicola A 2010. Nutritional genomics era: opportunities toward a genome-tailored nutritional regimen. J Nutr Biochem. 21(6):457–67.
  • [9] Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, et al. 1999 Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 656–660.
  • [10] Tolle V, Zizzari P, Tomasetto C, Rio MC, Epelbaum J, et al. 2001 In vivo and in vitro effects of ghrelin/motilin-related peptide on growth hormone secretion in the rat. Neuroendocrinology 54–61.
  • [11] Yang J, Brown MS, Liang G, Grishin NV, Goldstein JL 2008. Identification of the Acyltransferase that Octanoylates Ghrelin, an Appetite-Stimulating Peptide Hormone. Cell 387–396.
  • [12] Hassouna R, Zizzari P, Tolle V, 2010. The ghrelin/obestatin balance in the physiological and pathological control of GH secretion, body composition and food intake. Journal of Neuroendocrinology 794–804.
  • [13] Baessler, A., Hasinoff, M., Fischer, M. 2005. Genetic linkage and association of the growth hormone secretagogue receptor (ghrelin receptor) gene in human obesity. Diabetes. 54:259–67.
  • [14] Baessler, A, Fisher, M, Mayer, B. 2007. Epistatic interaction between haplotypes of the ghrelin ligand and receptor genes influence susceptibility to myocardial infarction and coronary artery disease. Human Molec Genet. 16:887–99.
  • [15] Zavarella, S., Petrone, A., Zampetti, S. 2008. A new variation in the promoter region, the −604 C>T and the Leu72Met polymorphism of the ghrelin gene are associated with the protection to insulin resistance. Int J Obes. 32:663–8.
  • [16] Gueorguiev, M., Lecoeur, C., Meyre, D., Benzinou, M., Mein, C. A., Hinney, A., Froguel, P. 2009. Association studies on ghrelin and ghrelin receptor gene polymorphisms with obesity. Obesity, 17(4), 745-754.
  • [17] Liu, B., Garcia, E. A., & Korbonits, M. 2011. Genetic studies on the ghrelin, growth hormone secretagogue receptor (GHSR) and ghrelin O-acyl transferase (GOAT) genes. Peptides, 32(11), 2191-2207.
  • [18] Alberti, K. G. M. M., & Zimmet, P. Z., 1998. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus. Provisional report of a WHO consultation. Diabetic medicine,15(7), 539-553.
  • [19] Gueorguiev M, Korbonits M, 2013. Genetics of the ghrelin system. Endocr Dev. Basel, Karger, 25, 25–40 (DOI: 10.1159/000348665).
  • [20] Joatar F, et al. 2017. Leu72Met and other ıntronic polymorphisms in the GHRLand GHSR genes are not associated with type 2 diabetes mellitus, ınsulin resistance, or serum ghrelin levels in a saudi population. Endocrinol Metab 32:360-369.
  • [21] Wang Y, et al. 2010. Ghrelin inhibits insulin secretion through the AMPK–UCP2 pathway in b cells. Federation of European Biochemical Societies Letters 201; 584, 1503–1508.
  • [22] Elabadlah H, Hameed R, D’Souza C, Mohsin S, Adeghate E, 2020. Exogenous ghrelin ıncreases plasma ınsulin level in diabetic rats. Biomolecules, 10, 633; doi:10.3390/biom10040633.
  • [23] Pulkkinen L, Ukkola O, Kolehmainen M, Uusitupa M, 2010. Ghrelin in diabetes and metabolic syndrome. International Journal of Peptides Volume Article ID 248948, 11 pages doi:10.1155/2010/248948.
  • [24] Chorley, B. N., Wang, X., Campbell, M. R., Pittman, G. S., Noureddine, M. A., & Bell, D. A. 2008. Discovery and verification of functional single nucleotide polymorphisms in regulatory genomic regions: current and developing technologies. Mutation Research/Reviews in Mutation Research, 659(1-2), 147-157.
  • [25] Choi HJ, et al. 2015. Polymorphisms in the ghrelin gene are associated with serum high-density lipoprotein cholesterol level and not with type 2 diabetes mellitus in koreans. The Journal of Clinical Endocrinology & Metabolism 91(11):4657– 4663.
  • [26] Mora M, Adam V, Palomera E, Blesa S, Díaz G, Buquet X, et al. 2015 Ghrelin Gene Variants Influence on Metabolic Syndrome Components in Aged Spanish Population. PLoS ONE 10(9): e0136931. doi:10.1371/journal.pone.0136931.
  • [27] Li P, et al. 2014. Genetic association analysis of 30 genes related to obesity in a european american population. Int J Obes (Lond). 38(5): 724–729. doi:10.1038/ijo.2013.140.
  • [28] Chung W, et al. 2009. Analysis of 30 genes (355 snps) related to energy homeostasis for association with adiposity in european-american and yup’ik eskimo populations. Hum Hered 67:193–205.
  • [29] Mager U, Degenhardt T, Pulkkinen L, Kolehmainen M, Tolppanen A-M, et al. 2008. Variations in the Ghrelin Receptor Gene Associate with Obesity and Glucose Metabolism in Individuals with Impaired Glucose Tolerance. PLoS ONE 3(8): e2941. doi:10.1371/journal.pone.0002941.
  • [30] Luglio HF, Inggriyani CG, Huriyat E, Julia M, Susilowat R, 2014. Int J Mol Epidemiol Genet 5(4):195-19.
Toplam 30 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Sağlık Kurumları Yönetimi
Bölüm Araştırma Makaleleri
Yazarlar

Esma Selçuk 0000-0002-1481-7834

Uğur Şahin 0000-0002-5629-3485

Didem Özkahraman 0000-0002-3951-0740

Mustafa Calapoğlu 0000-0002-9567-7270

Nilüfer Şahin Calapoğlu 0000-0002-7376-1607

Proje Numarası 4311-GÜP-15
Yayımlanma Tarihi 31 Ağustos 2022
Gönderilme Tarihi 12 Mayıs 2022
Yayımlandığı Sayı Yıl 2022 Cilt: 13 Sayı: 2

Kaynak Göster

Vancouver Selçuk E, Şahin U, Özkahraman D, Calapoğlu M, Şahin Calapoğlu N. Grelin ve Grelin Reseptörü Polimorfizmlerinin Tip 2 Diyabetle İlişkisi. Süleyman Demirel Üniversitesi Sağlık Bilimleri Dergisi. 2022;13(2):218-27.

SDÜ Sağlık Bilimleri Dergisi, makalenin gönderilmesi ve yayınlanması dahil olmak üzere hiçbir aşamada herhangi bir ücret talep etmemektedir. Dergimiz, bilimsel araştırmaları okuyucuya ücretsiz sunmanın bilginin küresel paylaşımını artıracağı ilkesini benimseyerek, içeriğine anında açık erişim sağlamaktadır.