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GLIS3 rs7020673 and rs10758593 polymorphisms interact in the susceptibility for type 1 diabetes mellitus

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Abstract

Aims

The transcription factor Gli-similar 3 (GLIS3) plays a key role in the development and maintenance of pancreatic beta cells as well as in the regulation of Insulin gene expression in adults. Accordingly, genome-wide association studies identified GLIS3 as a susceptibility locus for type 1 diabetes mellitus (T1DM) and glucose metabolism traits. Therefore, the aim of this study was to replicate the association of the rs10758593 and rs7020673 single nucleotide polymorphisms (SNPs) in the GLIS3 gene with T1DM in a Brazilian population.

Methods

Frequencies of the rs7020673 (G/C) and rs10758593 (A/G) SNPs were analyzed in 503 T1DM patients (cases) and in 442 non-diabetic subjects (controls). Haplotypes constructed from the combination of these SNPs were inferred using a Bayesian statistical method.

Results

Genotype and allele frequencies of rs7020673 and rs10758593 SNPs did not differ significantly between case and control groups. However, the frequency of ≥3 minor alleles of the analyzed SNPs in haplotypes was higher in T1DM patients compared to non-diabetic subjects (6.2 vs. 1.6%; P = 0.001). The presence of ≥3 minor alleles remained independently associated with risk of T1DM after adjustment for T1DM high-risk HLA DR/DQ haplotypes, age and ethnicity (OR = 3.684 95% CI 1.220–11.124). Moreover, levels of glycated hemoglobin seem to be higher in T1DM patients with rs10758593 A/A genotype than patients carrying the G allele of this SNP (P = 0.038), although this association was not kept after Bonferroni correction.

Conclusions

Our results indicate that individually the rs7020673 and rs10758593 SNPs are not significantly associated with T1DM but seem to interact in the predisposition for this disease.

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Acknowledgements

This study was supported by Grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (Grant Number: 482525/2013-4), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (Grant Number: 1928-2551/13-2), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, and Fundo de Incentivo à Pesquisa e Eventos at Hospital de Clínicas de Porto Alegre (Grant Number: 15-0003). D. Crispim, L.H.Canani, G.K.C.Duarte and T. S. Assmann are recipients of scholarships from CNPq, and B.M.S is recipient of scholarships from CAPES.

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Authors and Affiliations

  1. Endocrine Division, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, Prédio 12, 4º andar, Zip Code: 90035-003, Porto Alegre, Rio Grande do Sul, Brazil

    Guilherme C. K. Duarte, Tais S. Assmann, Cristine Dieter, Bianca M. de Souza & Daisy Crispim

  2. Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil

    Guilherme C. K. Duarte, Tais S. Assmann, Cristine Dieter, Bianca M. de Souza & Daisy Crispim

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  1. Guilherme C. K. Duarte
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Correspondence to Daisy Crispim.

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Ethical standard

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Hospital de Cl´ınicas de Porto Alegre research committee (Number of approval 15-0003) and with the 1964 Helsinki Declaration and its amendments or comparable ethical standards.

Human and animal rights

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (Comitê em Ética em Pesquisa do Hospital de Clinicas de Porto Alegre) and with the Helsinki Declaration of 1975, as revised in 2008. No animal was used in this study.

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Duarte, G.C.K., Assmann, T.S., Dieter, C. et al. GLIS3 rs7020673 and rs10758593 polymorphisms interact in the susceptibility for type 1 diabetes mellitus. Acta Diabetol 54, 813–821 (2017). https://doi.org/10.1007/s00592-017-1009-7

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