遗传学：LADA 只是迟发性 1 型糖尿病吗？
Genetics: Is LADA just late onset type 1 diabetes?
机构信息
Department of Endocrinology and Nutrition, University Hospital Arnau de Vilanova, Lleida, Spain.
Lleida Biomedical Research Institute (IRB Lleida), University of Lleida (UdL), Lleida, Spain.
出版信息
Front Endocrinol (Lausanne). 2022 Aug 10;13:916698. doi: 10.3389/fendo.2022.916698. eCollection 2022.
BACKGROUND
There is a controversy regarding Latent Autoimmune Diabetes in Adults (LADA) classification and whether it should be considered a slowly progressing form of type 1 (T1) diabetes (DM) or a distinct type of DM altogether.
METHODS
This cross-sectional study assessed major genes associated with T1DM (class II , [rs2476601] and [rs689]) in patients with LADA, as compared with participants with T1DM (stratified according to age of diagnosis before or after 30) and T2DM. HLA genotyping of the , and loci was performed by reverse PCR sequence-specific oligonucleotides. HLA haplotypes were assigned according to those most frequently described in the European population. and SNPs were genotyped by real-time PCR.
RESULTS
A total of 578 participants were included: 248 with T1DM (70 diagnosed after the age of 30), 256 with T2DM and 74 with LADA. High risk HLA alleles were significantly more frequent in LADA than in T2DM, whereas the opposite was true for protective alleles. We found a lower frequency of the high-risk DRB104-DQB103:02-DQA103:01 haplotype in LADA (21.1%) than in the overall T1DM (34.7%) (p<0.05), whereas no differences were found between these groups for DRB103-DQB102:01-DQA105:01 or for protective alleles. Only 12% the overall T1DM group had no risk alleles vs 30% of LADA (p<0.0005). However, HLA allele distribution was similar in LADA and T1DM diagnosed after the age of 30. A total of 506 individuals (195 with T1DM [21 diagnosed after age 30] 253 with T2DM and 58 with LADA) were genotyped for the and SNPs. The G/A genotype of the rs2476601 was more frequent and the T/T genotype of the SNP rs689 was less frequent in T1DM compared to LADA. We did not find any significant differences in the frequency of the mentioned SNPs between LADA and T2DM, or between LADA and T1DM diagnosed after the age of 30.
CONCLUSION
In this relatively small cross-sectional study, the genetic profile of subjects with LADA showed a similar T1DM-related risk allele distribution as in participants with T1DM diagnosed after the age of 30, but fewer risk alleles than those diagnosed before 30. Differences were present for HLA, as well as and genes.
背景
成人隐匿性自身免疫性糖尿病（LADA）的分类存在争议，其是否应被视为 1 型糖尿病（T1DM）的一种缓慢进展形式，还是一种完全不同的糖尿病类型。
方法
本横断面研究评估了与 T1DM 相关的主要基因（II 类，[rs2476601]和[rs689]）在 LADA 患者中的情况，将其与 T1DM 患者（根据诊断年龄<30 岁或>30 岁进行分层）和 T2DM 患者进行比较。通过反向 PCR 序列特异性寡核苷酸对 HLA 基因分型进行检测。根据欧洲人群中最常见的 HLA 单倍型进行分配。通过实时 PCR 对[rs2641741]和[SNP8646]进行基因分型。
结果
共纳入 578 名参与者：248 名 T1DM（70 名诊断年龄>30 岁），256 名 T2DM 和 74 名 LADA。LADA 中高风险 HLA 等位基因的频率明显高于 T2DM，而保护性等位基因则相反。我们发现 LADA（21.1%）中高风险 DRB104-DQB103:02-DQA103:01 单倍型的频率低于总体 T1DM（34.7%）（p<0.05），而这些组之间 DRB103-DQB102:01-DQA105:01 或保护性等位基因无差异。总体 T1DM 组中仅有 12%没有风险等位基因，而 LADA 组为 30%（p<0.0005）。然而，LADA 和 30 岁以后诊断的 T1DM 患者的 HLA 等位基因分布相似。共有 506 名个体（195 名 T1DM [21 名诊断年龄>30 岁]，253 名 T2DM 和 58 名 LADA）进行了[rs2476601]和[SNP8646]的基因分型。与 LADA 相比，T1DM 中 rs2476601 的 G/A 基因型更常见，SNP rs689 的 T/T 基因型更少见。我们未发现 LADA 和 T2DM 或 LADA 和 30 岁以后诊断的 T1DM 之间提到的 SNP 频率存在任何显著差异。
结论
在这项相对较小的横断面研究中，LADA 患者的遗传特征显示出与 30 岁以后诊断的 T1DM 患者相似的 T1DM 相关风险等位基因分布，但风险等位基因比 30 岁前诊断的患者少。HLA 以及[rs2641741]和[SNP8646]基因存在差异。
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