Konya bölgesi popülasyonunda CAPN10 genindeki SNP-43 polimorfizmi Tip 2 Diabetes riski ile ilişkilidir

Yıl 2021, , 290 - 294, 20.09.2021

Hülya Uçaryılmaz , Dudu Erkoç Kaya , Hilal Arıkoğlu Ahmet Bülent Turhan Mustafa Sait Gönen

https://doi.org/10.54005/geneltip.977573

Öz

Amaç: Kalpain-10 (CAPN10), Ca+2 bağımlı intrasellüler sistein proteazlar ailesinin atipik bir üyesidir. Birçok dokuda eksprese edilir ve başta insülin sekresyonu ve aktivitesi olmak üzere çok çeşitli hücresel fonksiyonlar için gereklidir. Tanımlanan ilk Tip 2 diyabet (T2D) yatkınlık genidir. Çalışmamızda bir Türk popülasyonunda CAPN10 gen polimorfizmleri (SNP-44, -43 ve -137) ile artmış T2D riski arasındaki ilişkinin analiz edilmesi amaçlandı.
Gereç ve Yöntem: Çalışmaya 149 T2D’li hasta ve 48 sağlıklı birey dahil edildi. Genotiplendirme PCR-SSCP tekniği kullanılarak yapıldı, dizi analizi ile doğrulandı. CAPN10 genotiopleri ile T2D gelişimi ve klinik özellikler arasındaki ilişki istatistiksel olarak analiz edildi.
Bulgular: Hastalıkla genotip arasındaki ilişkiyi belirlemek için yapılan odds analizi sonuçlarına göre; SNP-44 ile hastalık arasında ilişki gözlenmezken (OR: 1.417 CI:0.452-4.436, P=0.740), SNP-43 ile hastalık arasında anlamlı ilişki bulundu (OR: 0.455 CI:0.235-0.881, P=0.028). SNP-137 genotip dağılımı bakımından tüm hasta ve kontrol bireylerde C/C olarak tespit edildi. Taranan SNP’ler ile klinik parametreler arasında herhangi bir ilişki bulunmadı (P>0.05).
Sonuç: Sonuçlarımıza göre; CAPN10 genindeki SNP-43, Türk populasyonunda T2D gelişimi açısından bir risk faktörüdür.

Anahtar Kelimeler

Tip 2 Diyabet, Kalpain-10, polimorfizm

Destekleyen Kurum

Selçuk Üniversitesi Bilimsel Araştırma Projeleri (BAP) Koordinatörlüğü

Proje Numarası

09202049

SNP-43 polymorphism in CAPN10 gene is associated with Type 2 Diabetes risk in Konya region population

Öz

Objective: Calpain-10 (CAPN10) is an atypical member of the Ca2+ dependent intracellular cysteine proteases family. It is expressed in many tissues and is essential for multiple cellular functions such as insulin secretion and activity. It is the first type 2 diabetes susceptibility gene identified. In our study, we aimed to analyze the relationship between CAPN10 gene polymorphisms (SNP-44, -43 and -137) and increased type 2 diabetes risk in a Turkish population.
Material and Methods: 149 T2D patients and 48 healthy individuals were included in the study. Genotyping was performed using the PCR-SSCP technique, confirmed by DNA sequence analysis. The association between CAPN10 genotypes and T2D development and clinical features was statistically analyzed.
Results: According to the results of the odds analysis, while no correlation was observed between SNP-44 and disease (OR: 1.417 CI: 0.452-4.436, P=0.740), a significant correlation was found between SNP-43 and disease (OR: 0.455 CI: 0.235-0.881, P=0.028). In terms of SNP-137 genotype distribution, it was detected as C/C in all patient and control individuals. No correlation was found between the scanned SNPs and clinical parameters (P>0.05).
Conclusion: According to our results; SNP-43 in the CAPN10 gene is a risk factor for the development of T2D in the Turkish population.

Anahtar Kelimeler

Type 2 Diabetes, Calpain-10, polymorphism

Proje Numarası

09202049

Kaynakça

• 1. Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 1998;15:539-53.
• 2. Brestoff JR, Artis D. Immune regulation of metabolic homeostasis in health and disease. Cell 2015;161:146-60.
• 3. Vaiserman A, Lushchak O. Developmental origins of type 2 diabetes: Focus on epigenetics. Ageing Res Rev 2019;55:100957.
• 4. Weyer C, Bogardus C, Mott DM, Pratley RE. The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus. J Clin Invest 1999;104:787-94.
• 5. Lim EL, Hollingsworth KG, Aribisala BS, Chen MJ, Mathers JC, Taylor R. Reversal of type 2 diabetes: normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol. Diabetologia 2011;54:2506-14.
• 6. Donath MY, Shoelson SE. Type 2 diabetes as an inflammatory disease. Nat Rev Immunol 2011;11:98-107.
• 7. Zeggini E, Scott LJ, Saxena R, Voight BF. Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nat Genet 2008;40:638-45.
• 8. Guja C, Gagniuc P, Ionescu-Tirgovişte C. Genetic factors involved in the pathogenesis of type 2 diabetes. Proc Rom Acad Series B 2012;1:44-61.
• 9. Barroso I, Luan J, Middelberg RP, et al. Candidate gene association study in type 2 diabetes indicates a role for genes involved in beta-cell function as well as insülin action. PLoS Biol 2003;1:E20.
• 10. Panico P, Salazar AM, Burns AL, Ostosky-Wegman P. Role of calpain-10 in the development of diabetes mellitus and its complications. Arch Med Res 2014;45:103-15.
• 11. Horikawa Y, Oda N, Cox NJ, et al. Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus. Nat Genet 2000;26:163–75.
• 12. Suzuki K, Hata S, Kawabata Y, Sorimachi H. Structure, activation, and biology of calpain. Diabetes 2004;53:12–8.
• 13. Marshall C, Hitman GA, Partridge CJ, et al. Evidence that an isoform of Calpain-10 is a regulator of exocytosis in pancreatic β-cells. Mol Endocrinol 2005;19:213–24.
• 14. Dong B, Liu R. Characterization of endogenous and recombinant human calpain-10. Biochimie 2008;90:1362–71.
• 15. Ridderstråle M, Nilsson E. Type 2 diabetes candidate gene CAPN10: first, but not last. Curr Hypertens Rep 2008;10:19–24.
• 16. Baier LJ, Permana PA, Yang X, et al. A Calpain-10 gene polymorphism is associated with reduced muscle mRNA levels and insulin resistance. J Clin Invest 2000;106:R69–R73.
• 17. Evans JC, Frayling TM, Cassell PG, et al. Studies of association between the gene for Calpain-10 and Type 2 Diabetes Mellitus in United Kingdom. Am J Hum Genet 2001;69:544-52.
• 18. Cassell PG, Jackson AE, North BV, et al. Haplotype combinations of calpain 10 gene polymorphisms associate with increased risk of impaired glucose tolerance and type 2 diabetes in South Indians, Diabetes 2002;51:1622–28.
• 19. Garant MJ, Kao WH, Brancati F, et al. SNP43 of CAPN10 and the risk of type 2 Diabetes in African-Americans, The Atherosclerosis Risk in Communities Study, Diabetes 2002;51: 231–7.
• 20. Hoffstedt J, Ryden M, Lofgren P, Orho-Melander M, Groop L, Arner P. Polymorphism in the Calpain 10 gene influences glucose metabolism in human fat cells, Diabetologia 2002; 45:276–82.
• 21. Malecki MT, Moczulski DK, Klupa T, et al. Homozygous combination of calpain 10 gene haplotypes is associated with type 2 diabetes mellitus in a Polish population, Eur J Endocrinol 2002;146:695–9.
• 22. Horikawa Y, Oda N, Yu L, et al. Genetic variations in Calpain-10 gene are not a major factor in the occurrence of Type 2 Diabetes in Japanese. J Clin Endocrinol Metab 2003;88:244-7.
• 23. Horikawa Y. Calpain-10 (NIDDM1) as a susceptibility gene for common type 2 diabetes. Endocrine Journal 2006;53:567-76.
• 24. Tsai HJ, Sun G, Weeks DE, et al. Type 2 Diabetes and three Calpain-10 gene polymorphisms in Samoans: No Evidence of Association. Am J Hum Genet 2001;69:1236–44.
• 25. Elbein SC, Chu W, Ren Q, et al. Role of calpain-10 gene variants in familial type 2 diabetes in Caucasians. J Clin Endocr Metab 2002;87:650-4.
• 26. Fingerlin TE, Erdos MR, Watanabe RM, et al. Variation in three single nucleotide polymorphisms in the calpain-10 gene notassociated with type 2 diabetes in a large Finnish cohort. Diabetes 2002;51:1644–8.
• 27. Rasmussen SK, Urhammer SA, Berglund L, et al. Variants within the Calpain-10 gene on chromosome 2q37 (NIDDM1) and relationships to Type 2 Diabetes, insulin resistance and impaired acute insulin secretion among Scandinavian Caucasians. Diabetes 2002;51:3561-7.
• 28. Ortho-Malender M, Klannemark M, Svensson MK, Ridderstrale M, Lidgren CM, Groop L. Variants in the calpain-10 gene predispose to insülin resistance and elevated free fatty acid level. Diabetes 2002;51:2658–64.
• 29. Daimon M, Oizumi T, Saitoh T, et al. Calpain 10 gene polymorphisms are related, not to type 2 diabetes, but to increased serum cholesterol in Japanese. Diabetes Res Clin Pract 2002;56:147–52.
• 30. Shima Y, Nakanishi K, Odawara M, Kobayashi T, Ohta H. Association of the SNP-19 genotype 22 in the calpain-10 gene with elevated body mass index and hemoglobin A1c levels in Japanese. Clin Chim Acta 2003;336:89–96.
• 31. Song Y, Niu T, Manson JE, Kwiatkowski DJ, Liu S. Are variants in the CAPN10 gene related to risk of Type 2 diabetes? A quantitative assessment of population and family-based association studies. Am J Hum Genet 2004;74:208–22.
• 32. Wu B, Takahashi J, Fu M, Cheng H, Matsumura S, Taniguchi H. Variants of calpain-10 gene and its association with type 2 diabetes mellitus in a Chinese population. Diabetes Res Clin Pract 2005;68:155–61.
• 33. Kifagi C, Makni K, Mnif F, Boudawara M, Hamza N, Rekik N. Association of calpain-10 polymorphisms with type 2 diabetes in the Tunisian population. Diabetes Metab 2008;34:273–8.
• 34. Saez ME, Gonzalez-Sanchez JL, Ramirez-Lorca R, et al. The CAPN10 gene is associated with insulin resistance phenotypes in the Spanish population. PloS ONE 2008;3:e2953.
• 35. Adak S, Sengupta S, Chowdhury S, Bhattacharyya M. Co-existence of risk and protective haplotypes of Calpain 10 gene to type 2 diabetes in the eastern Indian population. Diab Vasc Dis Res 2010;7:63-8.
• 36. Demirci H, Yurtcu E, Ergun M, Yazıcı A, Karasu C, Yetkin I. Calpain-10 SNP-44 gene polymorphism affects susceptibility to type 2 diabetes mellitus and diabeticrelated conditions. Genet Test 2007;12:305-10.