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RNASEH1 gene variants are associated with autoimmune type 1 diabetes in Colombia

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Abstract

Background

In a previous work, we found linkage and association of type 1 diabetes (T1D) to a 12 known gene region at chromosome 2p25 in Colombian families. Here, we present further work on this candidate region.

Materials and methods

Seventeen SNPs located on the 12 candidate genes, in 100 familial trios set, were tested by ARMS–tetraprimer–PCR or PCR–RFLP. Five extra SNPs in the vicinity of rs10186193 were typed. A replica phase included 97 novel familial trios, in whom diabetes-related auto-antibodies (AABs) were tested in sera of the patients. In addition to transmission disequilibrium tests, haplotype analyses were carried out using the unphased software.

Results

SNP rs10186193 (at RNASEH1 gene) showed association with T1D (P = 0.005). The additional five SNPs revealed that rs7607888 (P = 2.03 × 10−7), rs55981318 (P = 0.018), and rs1136545 (P = 1.93 × 10−9) were also associated with T1D. Haplotype analysis showed association for rs55981318–rs10186193 (P = 0.0005), rs7563960–rs7607888 (P = 0.0007), rs7607888–rs1136545 (P = 9.21 × 10−10), and rs1136545–rs11538545 (P = 6.67 × 10−8). In contrast, the new set of 97 familial trios tested for SNPs rs55981318, rs10186193, and rs7607888 did not support the previous finding; however, by combining the sample (197 trios), evidence of association of T1D with rs55981318 and rs7607888 was conclusive. In addition, a two-loci haplotype analysis of the combined sample showed significant association of RNASEH1 with T1D (P = 3.1 × 10−5).

Conclusion

In conclusion, our analyses suggest that RNASEH1 gene variants associate with susceptibility/protection to T1D in Colombia.

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Acknowledgements

We are very grateful to the patients and their families for participating in this study. This study was funded by a Colciencias Grant # 1115-343-19156 and a CODI-Universidad de Antioquia Grant # 8704-2449.

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Authors and Affiliations

  1. Grupo Mapeo Genetico, Departamento de Pediatria, Facultad de Medicina, Universidad de Antioquia, Medellín, 050010470, Colombia

    N. Pineda-Trujillo, A. Rodríguez-Acevedo, A. Rodríguez, A. Rivera & J.-M. Alfaro

  2. Department of Biology, University College London, London, WC1E 6BT, UK

    A. Ruíz-Linares

  3. GENMOL, Instituto de Biologia, Universidad de Antioquia, Medellín, 1226, Colombia

    G. Bedoya

  4. Seccion de Endocrinología, Departamento de Pediatria, Universidad de Antioquia, Medellín, 1226, Colombia

    J.-M. Alfaro

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  1. N. Pineda-Trujillo
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Correspondence to N. Pineda-Trujillo.

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We do not have a conflict of interest to declare, related to this study.

Ethical approval

All procedures performed in this study were in accordance with the ethical standards of the institutional and with the 1964 Helsinki declaration and its later amendments.

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Informed consent was obtained from all participants included in this study.

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Pineda-Trujillo, N., Rodríguez-Acevedo, A., Rodríguez, A. et al. RNASEH1 gene variants are associated with autoimmune type 1 diabetes in Colombia. J Endocrinol Invest 41, 755–764 (2018). https://doi.org/10.1007/s40618-017-0797-5

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  • DOI: https://doi.org/10.1007/s40618-017-0797-5

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