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Electrochemiluminescence Assays for Human Islet Autoantibodies
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Genetics: Is LADA just late onset type 1 diabetes?

M Hernández1,2, Y Nóvoa-Medina3,4, R Faner5

  • 1Department of Endocrinology and Nutrition, University Hospital Arnau de Vilanova, Lleida, Spain.

Frontiers in Endocrinology
|August 29, 2022
PubMed
Summary
This summary is machine-generated.

Genetic analysis of Latent Autoimmune Diabetes in Adults (LADA) reveals distinct differences from type 1 diabetes (T1DM) and type 2 diabetes (T2DM). LADA shares some genetic risk factors with T1DM, particularly in later-onset cases, but also shows unique genetic profiles.

Keywords:
HLA class IIINSLADA (latent autoimmune diabetes in adults)PTPN22Type 1 diabetes mellitusage of onsetgenetics

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Area of Science:

  • Immunogenetics
  • Endocrinology
  • Diabetes Mellitus Classification

Background:

  • Ongoing debate exists regarding the classification of Latent Autoimmune Diabetes in Adults (LADA).
  • LADA's classification is contested: is it a slow-progressing type 1 diabetes (T1DM) or a distinct entity?
  • Understanding LADA's genetic underpinnings is crucial for accurate diagnosis and classification.

Purpose of the Study:

  • To investigate the genetic associations of LADA with T1DM and T2DM.
  • To compare the prevalence of major T1DM-associated genes (HLA, PTPN22, INS) in LADA patients versus T1DM and T2DM cohorts.
  • To clarify LADA's position within the diabetes mellitus spectrum through genetic profiling.

Main Methods:

  • Cross-sectional study involving 578 participants: 248 with T1DM, 256 with T2DM, and 74 with LADA.
  • Genotyping of class II HLA loci (DRB1, DQA1, DQB1) using reverse PCR sequence-specific oligonucleotides.
  • Genotyping of PTPN22 (rs2476601) and INS (rs689) SNPs via real-time PCR.

Main Results:

  • High-risk HLA alleles were more frequent in LADA than T2DM; protective alleles showed the opposite trend.
  • LADA patients exhibited a lower frequency of a specific high-risk HLA haplotype (DRB1*04-DQB1*03:02-DQA1*03:01) compared to overall T1DM.
  • Genetic profiles for PTPN22 and INS SNPs showed differences between LADA and T1DM, but not between LADA and T2DM or LADA and late-onset T1DM.

Conclusions:

  • The genetic profile of LADA partially resembles T1DM, particularly T1DM diagnosed later in life, but with fewer risk alleles.
  • Significant genetic differences were observed in HLA, PTPN22, and INS genes between LADA and other diabetes types.
  • Findings suggest LADA may represent a distinct subtype of diabetes with a unique genetic predisposition.