RNASEH1 基因变异与哥伦比亚的自身免疫性 1 型糖尿病有关。

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

机构信息

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

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

出版信息

J Endocrinol Invest. 2018 Jul;41(7):755-764. doi: 10.1007/s40618-017-0797-5. Epub 2017 Dec 4.

DOI:10.1007/s40618-017-0797-5

PMID:29204916

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), rs55981318 (P = 0.018), and rs1136545 (P = 1.93 × 10) 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), and rs1136545-rs11538545 (P = 6.67 × 10). 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).

CONCLUSION

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

摘要

背景

在之前的工作中，我们在哥伦比亚家族中发现了 1 型糖尿病（T1D）与染色体 2p25 上 12 个已知基因区域的连锁和关联。在这里，我们对这个候选区域进行了进一步的研究。

材料与方法

在 100 个家族三体型中，对位于 12 个候选基因上的 17 个 SNP 进行了 ARMS-四引物-PCR 或 PCR-RFLP 检测。对 rs10186193 附近的另外 5 个 SNP 进行了分型。在一个复制阶段，包括 97 个新的家族三体型，对患者血清中的糖尿病相关自身抗体（AAB）进行了检测。除了传递不平衡测试外，还使用非相位软件进行了单倍型分析。

结果

SNP rs10186193（位于 RNASEH1 基因）与 T1D 相关（P=0.005）。另外 5 个 SNP 显示 rs7607888（P=2.03×10）、rs55981318（P=0.018）和 rs1136545（P=1.93×10）也与 T1D 相关。单倍型分析显示 rs55981318-rs10186193（P=0.0005）、rs7563960-rs7607888（P=0.0007）、rs7607888-rs1136545（P=9.21×10）和 rs1136545-rs11538545（P=6.67×10）与 T1D 相关。相比之下，对新的 97 个家族三体型进行的 rs55981318、rs10186193 和 rs7607888 检测并没有支持之前的发现；然而，通过对样本（197 个三体型）进行合并，T1D 与 rs55981318 和 rs7607888 的关联是确凿的。此外，对合并样本的两基因座单倍型分析显示，RNASEH1 与 T1D 显著相关（P=3.1×10）。