Investigation of Insulin-Like Growth Factor 2 mRNA Binding Protein 2 Gene Polymorphisms in Type 2 Diabetes Patients

Yıl 2024, Cilt: 34 Sayı: 3, 332 - 336

Duygu Yolal Ertural Ümit Çınkır Nurcan Aras

https://doi.org/10.54005/geneltip.1418122

Öz

Background/Aims: Type 2 diabetes (T2D) whose prevalance differs in different populations is a multifactorial disease. T2D is describes a group of clinical syndromes resulting from glucose metabolism disorders triggered by genetic or environmental factors. Insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) gene participates in insulin signaling pathway and is involved in insulin secretion. SNPs in one of these genes, IGF2BP2 gene (rs1470579 and rs4402960), have been reported to partially increase the risk of type II diabetes. The aim of this study was to investigate in a Turkish population identified associations of IGF2BP2 variants rs4402960 and rs1470579 with T2D.
Methods: We genotyped two SNPs of IGF2BP2 gene, rs1470579 and rs4402960 in 100 healthy individuals and 100 patients. DNA isolation was performed on peripheral blood samples from patients and healthy groups. The molecular analysis of rs1470579 and rs4402960 polymorphisms of IGF2BP2 gene of each individual was performed by using Real-Time PCR (Applied Biosystems) method. Relationships of genotypes and alleles frequency of IGF2BP2 polymorphisms and T2D were examined by "Chi-square" or "Likelihood ratio" tests.
Results: As a result of the genotype and allele distributions; there was association between type II diabetes patients and control group for IGF2BP2 rs1470579 (A/C) gene polymorphism (p=0.0123). The frequency of AC genotype in patients is more than the control group. However, there was no statistically significant difference genotype distribution between the type 2 diabetes patients and control group for IGF2BP2 rs4402960 (G/T) gene polymorphisms. There was no association between the patients and the control group for TT and GG+GT genotype distribution (p=0.8847).
Conclusions: The results showed that the IGF2BP2 gene rs1470579 and rs4402960 polymorphisms were associated with T2D in a Turkish population (OR = 2.002, 95% CI 1.170–3.426, p < 0.05; OR = 1.879, 95% CI 1.110–3.182, p< 0.05). This is the first study between IGF2BP2 gene polymorphisms and type II diabetes in Turkish population.
Keywords: IGF2BP2, T2D, Polymorphism

Anahtar Kelimeler

IGF2BP2, T2D, Polymorphism

Proje Numarası

BAP-SBE TTB (DY) 2013-3 YL

Tip 2 Diyabet Hastalarında İnsülin Benzeri Büyüme Faktörü 2 mRNA Bağlayıcı Protein 2 Gen Polimorfizmlerinin Araştırılması

Öz

Amaç: Prevalansı farklı toplumlarda farklılık gösteren Tip 2 Diyabet (T2D) multifaktöriyel bir hastalıktır. T2D, genetik veya çevresel faktörler tarafından tetiklenen glikoz metabolizması bozukluklarından kaynaklanan bir grup klinik sendromu tanımlamaktadır. İnsülin benzeri büyüme faktörü 2 mRNA bağlayıcı protein 2 (IGF2BP2) geni, insülin sinyal yolağına katılır ve insülin salgılanmasında rol oynar. Bu gendeki polimorfizmlerin (rs1470579 ve rsS4402960) diyabet riskini kısmen artırdığı bildirilmiştir. Bu çalışmanın amacı, Türk toplumunda rs4402960 ve rs1470579 IGF2BP2 varyantlarının T2D ile olan ilişkilerini araştırmaktır.
Gereç ve Yöntem: IGF2BP2 geninin iki SNP'sini, rs1470579 ve rs4402960, 100 sağlıklı bireyde ve 100 hastada genotiplendirdik. DNA izolasyonu hasta ve sağlıklı gruplardan alınan periferik kan örnekleri üzerinde gerçekleştirilmiştir. Her bireyin IGF2BP2 genine ait rs1470579 ve rs4402960 polimorfizmlerinin moleküler analizi Real-Time PCR (Applied Biosystems) yöntemi kullanılarak gerçekleştirilmiştir. IGF2BP2 polimorfizmlerinin genotip ve alel sıklığı ile T2D arasındaki ilişkiler "Ki-kare" veya "Olabilirlik oranı" testleri ile incelenmiştir.
Bulgular: Genotip ve alel dağılımları sonucunda; IGF2BP2 rs1470579 (A/C) gen polimorfizmi için tip II diyabet hastaları ile kontrol grubu arasında ilişki bulunmuştur (p=0.0123). Hastalarda AC genotipinin sıklığı kontrol grubundan daha fazladır. Ancak, IGF2BP2 rs4402960 (G/T) gen polimorfizmleri için T2D hastaları ve kontrol grubu arasında genotip dağılımı açısından istatistiksel olarak anlamlı bir fark bulunmamıştır. TT ve GG+GT genotip dağılımı için hastalar ve kontrol grubu arasında bir ilişki bulunmamıştır (p=0.8847).
Sonuçlar: Sonuçlar, IGF2BP2 geni rs1470579 ve rs4402960 polimorfizmlerinin Türk toplumunda T2D ile ilişkili olduğunu göstermiştir (OR = 2.002, %95 CI 1.170-3.426, p < 0.05; OR = 1.879, %95 CI 1.110-3.182, p < 0.05). Bu çalışma, Türk toplumunda IGF2BP2 gen polimorfizmleri ile T2D arasındaki ilk çalışmadır.
Anahtar Kelimeler: IGF2BP2, T2D, Polimorfizm

Anahtar Kelimeler

IGF2BP2, Tip 2 Diyabet, Polimorfizm

Etik Beyan

Bu çalışma Mersin Üniversitesi Rektörlüğü Klinik Araştırmalar Etik Kurulu tarafından 22.11.2012 tarih ve 2012/370 karar sayısı ile onaylanmıştır.

Destekleyen Kurum

Mersin Üniversitesi Rektörlüğü Bilimsel Araştırma Projeler Birimi tarafından BAP-SBE TTB (DY) 2013-3 YL kodlu proje olarak desteklenmiştir.

Proje Numarası

BAP-SBE TTB (DY) 2013-3 YL

Teşekkür

Yüksek lisans eğitimim boyunca, her konuda bana yardımcı olan ve her zaman bana destek olan danışman hocam Prof. Dr. Nurcan Aras’a teşekkür ederim

Kaynakça

• Uma Jyothi K, Mohan Reddy B. Gene–gene and gene–environment interactions in the etiology of type 2 diabetes mellitus in the population of Hyderabad India. Meta Gene 2015;5: 9–20.
• International Diabetes Federation, IDF Diabetes Atlas. 7th ed. Belgium, Brussels. 2015.
• Desiderio A, Spinelli R, Ciccarelli M, Nigro C, Miele C, Beguinot F, et al. Epigenetics: spotlight on type 2 diabetes and obesity. Journal of Endocrinological Investigation 2016; 39: 1095-1103.
• Uma Jyothi K, Mohan Reddy B. Genetic etiology of type 2 diabetes mellitus: a review. International Journal of Diabetes in Developing Countries 2011; 31: 51-64.
• The Diabetes Genetics Replication and Meta-analysis (DIAGRAM) Consortium. Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. Nature genetics 2012; 44: 981-990.
• MacArthur J, Bowler E, Cerezo M, Gil L, Hall P, Hastings E, et al. The new NHGRI-EBI Catalog of published genome-wide association studies (GWAS Catalog). Nücleic acids research 2017; 45: 896-901.
• Groenewoud MJ, Dekker JM, Fritsche A, Nijpels G, Heine RJ, Maassen JA, et al. Variants of CDKAL1 and IGF2BP2 affect firstphase insulin secretion during hyperglycaemic clamps. Diabetologia 2008; 51:1659–1663.
• Koster JC, Marshall BA, Ensor N, Corbett JA, Nichols CG. Targeted overactivity of β cell K ATP channels induces profound neonatal diabetes. Cell 2000; 100: 645–654.
• Takeuchi F, Serizawa M, Yamamoto K, Fujisawa T, Nakashima E, Ohnaka K, et al. Confirmation of multiple risk loci and genetic impacts by a genome-wide association study of type 2 diabetes in the Japanese population. Diabetes 2009; 58: 1690–1699.
• Huang Q, Yin JY, Dai XP, Pei Q, Dong M, Zhou ZG, et al. IGF2BP2 variations influence repaglinide response and risk of type 2 diabetes in Chinese population. Acta Pharmacol Sin 2010; 31: 709–717.
• Zhang LF, Pei Q, Yang GP, Zhao YC, Mu YF, Huang Q, et al. The effect of IGF2BP2 gene polymorphisms on pioglitazone response in Chinese type 2 diabetes patients. Pharmacology 2014; 94(3-4), 115-122.
• Zeggini E, Weedon MN, Lindgren CM, Frayling TM, Elliott KS, Lango H, et al. Wellcome Trust Case Control Consortium (WTCCC), McCarthy MI, Hattersley AT. Replication of genome-wide association signals in uk samples reveals risk loci for type 2 diabetes. Science 2007; 316: 1336−1341.
• Christiansen J, Kolte AM, Hansen TO, Nielsen FC. IGF2 mRNA-binding protein 2: Biological function and putative role in type 2 diabetes. J Mol Endocrinol 2009;43: 187−195.
• Liu J, Song G, Zhao G, Meng T. Lack of association between IGF2BP2 rs4402960 polymorphism and gestational diabetes mellitus: a case–control study, meta-analysis and trial sequential analysis. Bioscience reports 2020; 40: 1-12.
• Cao J, Yan W, Ma X, Huang H, Yan H. Insulin-like Growth Factor 2 mRNA-Binding Protein 2—a Potential Link Between Type 2 Diabetes Mellitus and Cancer. The journal of clinical endocrinology & metabolism 2021; 106: 2807-2818.
• Wang J, Chen L, Qiang P. The role of IGF2BP2, an m6A reader gene, in human metabolic diseases and cancers. Cancer Cell International 2021; 21: 1-11.
• Wu XL, Lu RY, Wang LK, Wang YY, Dai YJ, Wang CY, et al. Long noncoding RNA HOTAIR silencing inhibits invasion and proliferation of human colon cancer LoVo cells via regulating IGF2BP2. J Cell Biochem 2018; 120:1221–31.
• Verma AK, Goyal Y, Bhatt D, Beg MMA, Dev K, Alsahli, MA, et al. Association between CDKAL1, HHEX, CDKN2A/2B and IGF2BP2 gene polymorphisms and susceptibility to type 2 diabetes in Uttarakhand, India. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 2021; 14, 23.
• Huang Q, Yin JY, Dai XP, Pei Q, Dong M, Zhou ZG, et al. IGF2BP2 variations influence repaglinide response and risk of type 2 diabetes in Chinese population. Acta Pharmacol Sin 2010; 31: 709–17.
• Zhao Y, Ma YS, Fang Y, Liu L, Wu SD, Fu D, et al. IGF2BP2 genetic variation and type 2 diabetes: a global meta-analysis. DNA Cell Biol 2012; 31:713–20.
• Grarup N, Rose CS, Andersson EA, Andersen G, Nielsen AL, Albrechtsen A, et al. Studies of association of variants near the HHEX, CDKN2A/B, and IGF2BP2 genes with type 2 diabetes and impaired insulin release in 10,705 Danish subjects: validation and extension of genome-wide association studies. Diabetes 2007; 56:3105–11.
• Zhang SM, Xiao JZ, Ren Q, Han XY, Tang Y, Yang WY, et al. Replication of association study between type 2 diabetes mellitus and IGF2BP2 in Han Chinese population. Chinese medical journal 2013; 126: 4013-4018.
• Tsai FJ, Yang CF, Chen CC, Chuang LM, Lu CH, Chang CT, et al. A genome-wide association study identifies susceptibility variants for type 2 diabetes in Han Chinese. PLoS Genet 2010; 6: 1000847.
• Shu XO, Long J, Cai Q, Qi L, Xiang YB, Cho YS, et al. Identification of new genetic risk variants for type 2 diabetes. PLoS Genet 2010; 6: 1001127.
• Cui B, Zhu X, Xu M, Guo T, Zhu D, Chen G, et al. A genome-wide association study confirms previously reported loci for type 2 diabetes in Han Chinese. PLoS One 2011; 6: e22353.
• Li H, Gan W, Lu L, Dong X, Han X, Hu C, et al. A Genome-Wide Association Study identifies GRK5 and RASGRP1 as type 2 diabetes loci in Chinese Hans. Diabetes 2013; 62: 291-298.
• Rao P, Wang H, Fang H, Gao Q, Zhang J, Song M, et al. Association between IGF2BP2 polymorphisms and type 2 diabetes mellitus: a case–control study and meta-analysis. International journal of environmental research and public health 2016; 13: 574.