Addison's Disease Occurring in Sisters

Hewitt, Paul

doi:10.1136/bmj.2.5060.1530

Cited by 21 publications

(7 citation statements)

References 5 publications

(2 reference statements)

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“…The first case report of monozygotic twins concordant for AAD, suggesting a genetic aetiology, was published more than 40 years ago [3] and a number of similar cases have since been reported [4]–[6]. The observation that AAD, in common with many other autoimmune conditions, sometimes clusters within families also supports a genetic basis for the condition [7], [8]. Furthermore, individuals with AAD are predisposed to develop other organ-specific autoimmune diseases which suggests shared susceptibility loci for these conditions.…”

Section: Introductionmentioning

confidence: 92%

Association of Autoimmune Addison's Disease with Alleles of STAT4 and GATA3 in European Cohorts

et al. 2014

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BackgroundGene variants known to contribute to Autoimmune Addison's disease (AAD) susceptibility include those at the MHC, MICA, CIITA, CTLA4, PTPN22, CYP27B1, NLRP-1 and CD274 loci. The majority of the genetic component to disease susceptibility has yet to be accounted for.AimTo investigate the role of 19 candidate genes in AAD susceptibility in six European case-control cohorts.MethodsA sequential association study design was employed with genotyping using Sequenom iPlex technology. In phase one, 85 SNPs in 19 genes were genotyped in UK and Norwegian AAD cohorts (691 AAD, 715 controls). In phase two, 21 SNPs in 11 genes were genotyped in German, Swedish, Italian and Polish cohorts (1264 AAD, 1221 controls). In phase three, to explore association of GATA3 polymorphisms with AAD and to determine if this association extended to other autoimmune conditions, 15 SNPs in GATA3 were studied in UK and Norwegian AAD cohorts, 1195 type 1 diabetes patients from Norway, 650 rheumatoid arthritis patients from New Zealand and in 283 UK Graves' disease patients. Meta-analysis was used to compare genotype frequencies between the participating centres, allowing for heterogeneity.ResultsWe report significant association with alleles of two STAT4 markers in AAD cohorts (rs4274624: P = 0.00016; rs10931481: P = 0.0007). In addition, nominal association of AAD with alleles at GATA3 was found in 3 patient cohorts and supported by meta-analysis. Association of AAD with CYP27B1 alleles was also confirmed, which replicates previous published data. Finally, nominal association was found at SNPs in both the NF-κB1 and IL23A genes in the UK and Italian cohorts respectively.ConclusionsVariants in the STAT4 gene, previously associated with other autoimmune conditions, confer susceptibility to AAD. Additionally, we report association of GATA3 variants with AAD: this adds to the recent report of association of GATA3 variants with rheumatoid arthritis.

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Section: Introductionmentioning

confidence: 92%

Association of Autoimmune Addison's Disease with Alleles of STAT4 and GATA3 in European Cohorts

et al. 2014

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“…Despite its rarity, AAD displays high concordance rates in twins and aggregation in families, suggesting a strong genetic contribution [12][13][14][15][16][17][18]. A recent twin concordance study (Skov J. et al, submitted) reports a heritability higher than that of, for instance, type 1 diabetes mellitus (0.69-0.88) [19][20][21][22][23] and Graves' disease (0.79) [24] .…”

Section: Introductionmentioning

confidence: 99%

Extended exome sequencing identifies BACH2 as a novel major risk locus for Addison's disease

Eriksson¹,

Bianchi

Landegren

et al. 2016

J Intern Med

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Background Autoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addison's disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology. Methods To understand the genetic background of Addison's disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected set of 1853 genes and their potential regulatory elements, for the purpose of sequencing 479 patients with Addison's disease and 1394 controls. Results We identified BACH2 (rs62408233‐A, OR = 2.01 (1.71–2.37), P = 1.66 × 10−15, MAF 0.46/0.29 in cases/controls) as a novel gene associated with Addison's disease development. We also confirmed the previously known associations with the HLA complex. Conclusion Whilst BACH2 has been previously reported to associate with organ‐specific autoimmune diseases co‐inherited with Addison's disease, we have identified BACH2 as a major risk locus in Addison's disease, independent of concomitant autoimmune diseases. Our results may enable future research towards preventive disease treatment.

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“…Since then several other cases have been recorded (Br0chner-Mortensen, 1956;Hewitt, 1957;Meakin et al, 1959;Shepard et a-t., 1959).…”

Section: Commentmentioning

confidence: 97%

Addison's Disease in Identical Twins

Smith¹,

Gough²,

Galpin³

1963

BMJ

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Addison's Disease Occurring in Sisters

Cited by 21 publications

References 5 publications

Association of Autoimmune Addison's Disease with Alleles of STAT4 and GATA3 in European Cohorts

Association of Autoimmune Addison's Disease with Alleles of STAT4 and GATA3 in European Cohorts

Extended exome sequencing identifies BACH2 as a novel major risk locus for Addison's disease

Addison's Disease in Identical Twins

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