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Association of two synonymous splicing-associated CpG single nucleotide polymorphisms in calpain 10 and solute carrier family 2 member 2 with type 2 diabetes

  • Authors:
    • Maria Karambataki
    • Andigoni Malousi
    • Georgios Tzimagiorgis
    • Constantinos Haitoglou
    • Aikaterini Fragou
    • Elisavet Georgiou
    • Foteini Papadopoulou
    • Gerasimos E. Krassas
    • Sofia Kouidou
  • View Affiliations / Copyright

    Affiliations: Laboratory of Biological Chemistry, Department of Medicine, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece, Department of Endocrinology, Diabetes and Metabolism, Panagia General Hospital, Thessaloniki 55132, Greece
    Copyright: © Karambataki et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 146-158
    |
    Published online on: December 29, 2016
       https://doi.org/10.3892/br.2016.833
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Abstract

Coding synonymous single nucleotide polymorphisms (SNPs) have attracted little attention until recently. However, such SNPs located in epigenetic, CpG sites modifying exonic splicing enhancers (ESEs) can be informative with regards to the recently verified association of intragenic methylation and splicing. The present study describes the association of type 2 diabetes (T2D) with the exonic, synonymous, epigenetic SNPs, rs3749166 in calpain 10 (CAPN10) glucose transporter (GLUT4) translocator and rs5404 in solute carrier family 2, member 2 (SLC2A2), also termed GLUT2, which, according to prior bioinformatic analysis, strongly modify the splicing potential of glucose transport-associated genes. Previous association studies reveal that only rs5404 exhibits a strong negative T2D association, while data on the CAPN10 polymorphism are contradictory. In the present study DNA from blood samples of 99 Greek non-diabetic control subjects and 71 T2D patients was analyzed. In addition, relevant publicly available cases (40) resulting from examination of 110 Personal Genome Project data files were analyzed. The frequency of the rs3749166 A allele, was similar in the patients and non-diabetic control subjects. However, AG heterozygotes were more frequent among patients (73.24% for Greek patients and 54.55% for corresponding non-diabetic control subjects; P=0.0262; total cases, 52.99 and 75.00%, respectively; P=0.0039). The rs5404 T allele was only observed in CT heterozygotes (Greek non-diabetic control subjects, 39.39% and Greek patients, 22.54%; P=0.0205; total cases, 34.69 and 21.28%, respectively; P=0.0258). Notably, only one genotype, heterozygous AG/CC, was T2D-associated (Greek non-diabetic control subjects, 29.29% and Greek patients, 56.33%; P=0.004; total cases, 32.84 and 56.58%, respectively; P=0.0008). Furthermore, AG/CC was strongly associated with very high (≥8.5%) glycosylated plasma hemoglobin levels among patients (P=0.0002 for all cases). These results reveal the complex heterozygotic SNP association with T2D, and indicate possible synergies of these epigenetic, splicing-regulatory, synonymous SNPs, which modify the splicing potential of two alternative glucose transport-associated genes.
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1 

Romero PR, Zaidi S, Fang YY, Uversky VN, Radivojac P, Oldfield CJ, Cortese MS, Sickmeier M, LeGall T, Obradovic Z, et al: Alternative splicing in concert with protein intrinsic disorder enables increased functional diversity in multicellular organisms. Proc Natl Acad Sci USA. 103:8390–8395. 2006. View Article : Google Scholar : PubMed/NCBI

2 

Stamm S, BenAri S, Rafalska I, Tang Y, Zhang Z, Toiber D, Thanaraj TA and Soreq H: Function of alternative splicing. Gene. 344:1–20. 2005. View Article : Google Scholar : PubMed/NCBI

3 

Soukarieh O, Gaildrat P, Hamieh M, Drouet A, BaertDesurmont S, Frébourg T, Tosi M and Martins A: Exonic splicing mutations are more prevalent than currently estimated and can be predicted by using in silico tools. PLoS Genet. 12:e10057562016. View Article : Google Scholar : PubMed/NCBI

4 

Cartegni L, Wang J, Zhu Z, Zhang MQ and Krainer AR: ESEfinder: a web resource to identify exonic splicing enhancers. Nucleic Acids Res. 31:3568–3571. 2003. View Article : Google Scholar : PubMed/NCBI

5 

Anastasiadou C, Malousi A, Maglaveras N and Kouidou S: Human epigenome data reveal increased CpG methylation in alternatively spliced sites and putative exonic splicing enhancers. DNA Cell Biol. 30:267–275. 2011. View Article : Google Scholar : PubMed/NCBI

6 

Ong CT and Corces VG: CTCF: an architectural protein bridging genome topology and function. Nat Rev Genet. 15:234–246. 2014. View Article : Google Scholar : PubMed/NCBI

7 

Malousi A and Kouidou S: DNA hypermethylation of alternatively spliced and repeat sequences in humans. Mol Genet Genomics. 287:631–642. 2012. View Article : Google Scholar : PubMed/NCBI

8 

Shoemaker R, Deng J, Wang W and Zhang K: Allele-specific methylation is prevalent and is contributed by CpG-SNPs in the human genome. Genome Res. 20:883–889. 2010. View Article : Google Scholar : PubMed/NCBI

9 

Scalet D, Balestra D, Rohban S, Bovolenta M, Perrone D, Bernardi F, Campaner S and Pinotti M: Exploring splicing-switching molecules for seckel syndrome therapy. Biochim Biophys Acta. 1863:15–20. 2016. View Article : Google Scholar : PubMed/NCBI

10 

Karambataki M, Malousi A, Maglaveras N and Kouidou S: Synonymous polymorphisms at splicing regulatory sites are associated with CpGs in neurodegenerative disease-related genes. Neuromolecular Med. 12:260–269. 2010. View Article : Google Scholar : PubMed/NCBI

11 

Karambataki M, Malousi A and Kouidou S: Risk-associated coding synonymous SNPs in type 2 diabetes and neurodegenerative diseases: Genetic silence and the underrated association with splicing regulation and epigenetics. Mutat Res. 770:85–93. 2014. View Article : Google Scholar : PubMed/NCBI

12 

Harlid S, Ivarsson MI, Butt S, Hussain S, Grzybowska E, Eyfjörd JE, Lenner P, Försti A, Hemminki K, Manjer J, et al: A candidate CpG SNP approach identifies a breast cancer associated ESR1-SNP. Int J Cancer. 129:1689–1698. 2011. View Article : Google Scholar : PubMed/NCBI

13 

Imamura M and Maeda S: Genetics of type 2 diabetes: the GWAS era and future perspectives (Review). Endocr J. 58:723–739. 2011. View Article : Google Scholar : PubMed/NCBI

14 

Kurzawski M, Dziewanowski K, Kedzierska K, Gornik W, Banas A and Drozdzik M: Association of calpain-10 gene polymorphism and posttransplant diabetes mellitus in kidney transplant patients medicated with tacrolimus. Pharmacogenomics J. 10:120–125. 2010. View Article : Google Scholar : PubMed/NCBI

15 

Shchetynsky K, Protsyuk D, Ronninger M, DiazGallo LM, Klareskog L and Padyukov L: Gene-gene interaction and RNA splicing profiles of MAP2K4 gene in rheumatoid arthritis. Clin Immunol. 158:19–28. 2015. View Article : Google Scholar : PubMed/NCBI

16 

Brown AE, Yeaman SJ and Walker M: Targeted suppression of calpain-10 expression impairs insulin-stimulated glucose uptake in cultured primary human skeletal muscle cells. Mol Genet Metab. 91:318–324. 2007. View Article : Google Scholar : PubMed/NCBI

17 

Alsaraj F, O'Gorman D, McAteer S, McDermott J, Hawi Z and Sreenan S: Haplotype association of calpain 10 gene variants with type 2 diabetes mellitus in an Irish sample. Ir J Med Sci. 179:269–272. 2010. View Article : Google Scholar : PubMed/NCBI

18 

Song Y, You NC, Hsu YH, Sul J, Wang L, Tinker L, Eaton CB and Liu S: Common genetic variation in calpain-10 gene (CAPN10) and diabetes risk in a multi-ethnic cohort of American postmenopausal women. Hum Mol Genet. 16:2960–2971. 2007. View Article : Google Scholar : PubMed/NCBI

19 

Barroso I, Luan J, Middelberg RP, Harding AH, Franks PW, Jakes RW, Clayton D, Schafer AJ, O'Rahilly S and Wareham NJ: Candidate gene association study in type 2 diabetes indicates a role for genes involved in beta-cell function as well as insulin action. PLoS Biol. 1:E202003. View Article : Google Scholar : PubMed/NCBI

20 

Laukkanen O, Lindström J, Eriksson J, Valle TT, Hämäläinen H, Ilanne-Parikka P, Keinänen-Kiukaanniemi S, Tuomilehto J, Uusitupa M and Laakso M: Finnish Diabetes Prevention Study: Polymorphisms in the SLC2A2 (GLUT2) gene are associated with the conversion from impaired glucose tolerance to type 2 diabetes: The Finnish Diabetes Prevention Study. Diabetes. 54:2256–2260. 2005. View Article : Google Scholar : PubMed/NCBI

21 

Kilpeläinen TO, Lakka TA, Laaksonen DE, Mager U, Salopuro T, Kubaszek A, Todorova B, Laukkanen O, Lindström J, Eriksson JG, et al: Finnish Diabetes Prevention Study Group: Interaction of single nucleotide polymorphisms in ADRB2, ADRB3, TNF, IL6, IGF1R, LIPC, LEPR, and GHRL with physical activity on the risk of type 2 diabetes mellitus and changes in characteristics of the metabolic syndrome: The Finnish Diabetes Prevention Study. Metabolism. 57:428–436. 2008. View Article : Google Scholar : PubMed/NCBI

22 

Willer CJ, Bonnycastle LL, Conneely KN, Duren WL, Jackson AU, Scott LJ, Narisu N, Chines PS, Skol A, Stringham HM, et al: Screening of 134 single nucleotide polymorphisms (SNPs) previously associated with type 2 diabetes replicates association with 12 SNPs in nine genes. Diabetes. 56:256–264. 2007. View Article : Google Scholar : PubMed/NCBI

23 

American Diabetes Association, . Standards of medical care in diabetes - 2013. Diabetes Care. 36:(Suppl 1). S11–S66. 2013. View Article : Google Scholar : PubMed/NCBI

24 

Ye J, Coulouris G, Zaretskaya I, Cutcutache I, Rozen S and Madden TL: Primer-BLAST: A tool to design target-specific primers for polymerase chain reaction. BMC Bioinformatics. 13:1342012. View Article : Google Scholar : PubMed/NCBI

25 

Church GM: The personal genome project. Mol Syst Biol. 1:2005.0030. 2005. View Article : Google Scholar

26 

Chen HH, Wang YC and Fann MJ: Identification and characterization of the CDK12/cyclin L1 complex involved in alternative splicing regulation. Mol Cell Biol. 26:2736–2745. 2006. View Article : Google Scholar

27 

Tian C, Yan R, Wen S, Li X, Li T, Cai Z, Li X, Du H and Chen H: A splice mutation and mRNA decay of EXT2 provoke hereditary multiple exostoses. PLoS One. 9:e948482014. View Article : Google Scholar : PubMed/NCBI

28 

Strohman RC: Linear genetics, non-linear epigenetics: complementary approaches to understanding complex diseases. Integr Physiol Behav Sci. 30:273–282. 1995. View Article : Google Scholar : PubMed/NCBI

29 

Lau E: Non-coding RNA: Zooming in on lncRNA functions. Nat Rev Genet. 15:574–575. 2014. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Karambataki M, Malousi A, Tzimagiorgis G, Haitoglou C, Fragou A, Georgiou E, Papadopoulou F, Krassas GE and Kouidou S: Association of two synonymous splicing-associated CpG single nucleotide polymorphisms in calpain 10 and solute carrier family 2 member 2 with type 2 diabetes. Biomed Rep 6: 146-158, 2017.
APA
Karambataki, M., Malousi, A., Tzimagiorgis, G., Haitoglou, C., Fragou, A., Georgiou, E. ... Kouidou, S. (2017). Association of two synonymous splicing-associated CpG single nucleotide polymorphisms in calpain 10 and solute carrier family 2 member 2 with type 2 diabetes. Biomedical Reports, 6, 146-158. https://doi.org/10.3892/br.2016.833
MLA
Karambataki, M., Malousi, A., Tzimagiorgis, G., Haitoglou, C., Fragou, A., Georgiou, E., Papadopoulou, F., Krassas, G. E., Kouidou, S."Association of two synonymous splicing-associated CpG single nucleotide polymorphisms in calpain 10 and solute carrier family 2 member 2 with type 2 diabetes". Biomedical Reports 6.2 (2017): 146-158.
Chicago
Karambataki, M., Malousi, A., Tzimagiorgis, G., Haitoglou, C., Fragou, A., Georgiou, E., Papadopoulou, F., Krassas, G. E., Kouidou, S."Association of two synonymous splicing-associated CpG single nucleotide polymorphisms in calpain 10 and solute carrier family 2 member 2 with type 2 diabetes". Biomedical Reports 6, no. 2 (2017): 146-158. https://doi.org/10.3892/br.2016.833
Copy and paste a formatted citation
x
Spandidos Publications style
Karambataki M, Malousi A, Tzimagiorgis G, Haitoglou C, Fragou A, Georgiou E, Papadopoulou F, Krassas GE and Kouidou S: Association of two synonymous splicing-associated CpG single nucleotide polymorphisms in calpain 10 and solute carrier family 2 member 2 with type 2 diabetes. Biomed Rep 6: 146-158, 2017.
APA
Karambataki, M., Malousi, A., Tzimagiorgis, G., Haitoglou, C., Fragou, A., Georgiou, E. ... Kouidou, S. (2017). Association of two synonymous splicing-associated CpG single nucleotide polymorphisms in calpain 10 and solute carrier family 2 member 2 with type 2 diabetes. Biomedical Reports, 6, 146-158. https://doi.org/10.3892/br.2016.833
MLA
Karambataki, M., Malousi, A., Tzimagiorgis, G., Haitoglou, C., Fragou, A., Georgiou, E., Papadopoulou, F., Krassas, G. E., Kouidou, S."Association of two synonymous splicing-associated CpG single nucleotide polymorphisms in calpain 10 and solute carrier family 2 member 2 with type 2 diabetes". Biomedical Reports 6.2 (2017): 146-158.
Chicago
Karambataki, M., Malousi, A., Tzimagiorgis, G., Haitoglou, C., Fragou, A., Georgiou, E., Papadopoulou, F., Krassas, G. E., Kouidou, S."Association of two synonymous splicing-associated CpG single nucleotide polymorphisms in calpain 10 and solute carrier family 2 member 2 with type 2 diabetes". Biomedical Reports 6, no. 2 (2017): 146-158. https://doi.org/10.3892/br.2016.833
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