Rare Diseases Symptoms Automatic Extraction

CYP21A2 polymorphisms in patients with autoimmune Addison's disease, and linkage disequilibrium to HLA risk alleles.

[congenital adrenal hyperplasia]

Objective: Steroid 21-hydroxylase (21OH), encoded by CYP21A2, is the major autoantigen in autoimmune Addison's disease (AAD). CYP21A2 is located in the region of the human leukocyte antigen (HLA) complex on chromosome 6p21.3, which harbours several risk alleles for AAD. The objective was to investigate whether CYP21A2 gene variants confer risk of AAD independently of other risk alleles in the HLA loci. Design: DNA samples from 381 Norwegian patients with AAD and 340 healthy controls (HC) previously genotyped for the HLA-A, -B, -DRB1, and -DQB1 and MICA loci were used for genotyping of CYP21A2. Methods: Genotyping of CYP21A2 was performed by direct sequencing. Linkage of CYP21A2 to the HLA loci was assessed using UNPHASED version 3.0.10 and PHASE version 2.1. Results: Heterozygotes of the single nucleotide polymorphisms (SNPs) rs397515394, rs6467, rs6474, rs76565726 and rs6473 were detected significantly more frequently in AAD patients compared to HC (P < 0.005), but all SNPs were in linkage disequilibrium (LD) with high-risk HLA-DRB1 haplotypes. rs6472C protected against AAD (Odds ratio = 0.15, 95% confidence interval [0.08 - 0.30], P = 3.8 e-10). This SNP was not in LD with HLA loci (P = 0.02), but did not increase protection when considering the effect of HLA-DRB1 alleles. Mutations causing congenital adrenal hyperplasia were found in heterozygosity in < 1.5 % of the cases in both groups. Conclusion: Genotypes of CYP21A2 associated with AAD are in LD with the main autoimmune AAD risk loci HLA-DRB1 and do not constitute an independent genetic susceptibility locus.

Diseases presenting "single nucleotide polymorphisms" symptom

  • adrenomyeloneuropathy
  • alpha-thalassemia
  • benign recurrent intrahepatic cholestasis
  • congenital adrenal hyperplasia
  • dentin dysplasia
  • esophageal adenocarcinoma
  • esophageal carcinoma
  • esophageal squamous cell carcinoma
  • familial hypocalciuric hypercalcemia
  • hirschsprung disease
  • neonatal adrenoleukodystrophy
  • oculocutaneous albinism
  • oligodontia
  • pendred syndrome
  • primary effusion lymphoma
  • scrub typhus
  • triple a syndrome
  • waldenström macroglobulinemia

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