Searchable abstracts of presentations at key conferences in endocrinology
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21st Joint Meeting of the British Endocrine Societies

ea0003p152 | Genetics | BES2002

No association of a 3' UTR polymorphism of the interleukin-12 P40 (IL12B) gene with Grave's disease in a UK population

Heward J , Allahabadia A , Franklyn J , Gough S

Graves' disease (GD) is an autoimmune disorder of the thyroid gland, of which the aetiology is unknown, but susceptibility to disease is thought to result from both genetic and environmental factors. Familial clustering data suggests that GD is a polygenic disorder, with laboratory studies identifying the HLA gene region and the CTLA-4 gene region as susceptibility loci. However, together the HLA region and the CTLA-4 gene regions only contribute about 50% towards the genetic ...

ea0003p153 | Genetics | BES2002

Lack of association of the insulin gene region with Grave's disease in the UK

Tait K , Collins J , Heward J , Allahbadia A , Barnett A , Franklyn J , Gough S

Graves' disease and type 1 diabetes frequently occur together and this would suggest that genetic susceptibility is due to common loci. The insulin (INS) gene region (IDDM2) on chromosome 11p15.5 is linked to, and associated with, type 1 diabetes and it has been suggested that it may be acting as a general autoimmunity locus. Susceptibility is conferred by the variable number of tandem repeats (VNTR); a polymorphic region situated 5' to the INS gene. The class I/I homozygote g...

ea0003p154 | Genetics | BES2002

The angiotensin II response to an acute exercise stimulus and the angiotensin converting enzyme (ACE) genotype

Woods D , Jones A , Sanders J , Hurel S , Jamshidi Y , Hawe E , Goldstone J , Gohlke P , Humphries S , Montgomery H

The ACE I/D polymorphism is associated with resting ACE activity such that DD>ID>II. The D allele is strongly associated with increased exercise-induced left ventricular hypertrophy (LVH) and cardiovascular risk.Objective: Examine the relation between ACE genotype, exercise, circulating ACE and angiotensin II.Ethical approval was obtained and 17 (9DD, 8II) healthy, male (22.9+/-1.9 years, 178.6+/-2.8cm, 71.9+/-2.2kg) Caucasi...

ea0003p155 | Genetics | BES2002

A nonsense mutation in exon two of the DNASE1 gene is not present in UK subjects with SLE and autoimmune thyroid disease

Simmonds M , Heward J , Allahabadia A , Foxall H , Gordon C , Franklyn J , Gough S

Systemic lupus erythematosus (SLE) is characterised by the activation of autoreactive T and B cells and the production of autoantibodies. Concordance rates in monozygotic and dizygotic twins, along with familial clustering, suggest that SLE has a strong genetic component. Moreover, the co-existence of SLE and other autoimmune diseases within individuals, including autoimmune thyroid disease (ATD), suggests a sharing of general autoimmune susceptibility loci. Case control studi...

ea0003p156 | Genetics | BES2002

Seven novel mutations in the androgen receptor gene associated with complete androgen insensitivity syndrome

Jaaskelainen J , Mongan N , Martin H , Hughes I

Complete androgen insensitivity syndrome (CAIS), is generally caused by a mutation in the androgen receptor (AR) gene. In sequencing genomic DNA from patients with CAIS, we identified 7 novel mutations in the AR. Their effects on AR function are speculated in relation to AR functional domains and crystal structure. Local Ethical Committee approval was obtained for the use of patient samples.Exon 1 mutations, Q86X and Y480X, are located in the transactiv...

ea0003p157 | Genetics | BES2002

Compound heterozygous AIRE-1 mutations in autoimmune polyendocrinopathy type 1

Bowl M , Turner J , Nesbit M , Harding B , Thakker R

Autoimmune polyendocrinopathy type 1 (APS1) is an autosomal recessive disorder characterised by hypoparathyroidism, adrenocortical failure, and mucocutaneous candidiasis. The gene causing APS1 is the autoimmune regulator (AIRE-1) gene, which maps to 21q22.3 and consists of 14 exons. The AIRE-1 protein, comprising of 545 amino acids, contains two PHD zinc-finger motifs, a proline rich region and four LXXLL motifs, consistent with its role as a transcription factor. Over 25 diff...

ea0003p158 | Genetics | BES2002

Lack of association between polymorphic markers within 11b-hydroxysteroid dehydrogenase type 1 gene (HSD11B1) and obesity

Draper N , Echwald S , Sorensen T , Astrup A , Lavery G , Chalder S , Hewison M , Pedersen O , Stewart P

11beta-hydroxysteroid dehydrogenase regulates glucocorticoid action, by interconverting cortisone (E) to cortisol (F). The Type 1 isozyme (11betaHSD1) is an oxoreductase expressed in adipose tissue, where it may play a role in the pathogenesis of visceral obesity.We have characterised two polymorphic (CA)n microsatellite markers within intron 4 of the HSD11B1 gene, termed (CA)15 and (CA)19. In an earlier study evaluating a 'normal' population (MONICA co...

ea0003p159 | Genetics | BES2002

Single nucleotide polymorphisms of the beta2-adrenergic receptor (ADRB2) gene and hypertension

Brain N , Tomaszewski M , Lacka B , Charchar F , Wang W , Padhmanaban S , Anderson N , Zukowska-Szczechowska E , Grzeszczak W , Dominiczak A

Objective: Three nonsynonomous SNPs, Arg16Gly, Gln27Glu and Thr164Ile, in the coding region of the ADRB2 gene affect either receptor affinity or trafficking. Their distribution has been shown to differ significantly in hypertension. We investigated the association of these loci with hypertension in the Silesian Hypertension Study.Methods: Following local ethics approval, 274 unrelated Polish subjects consisting of 146 hypertensives and 128 normotensives ...

ea0003p160 | Genetics | BES2002

Independent Y chromosome markers associated with blood pressure and testosterone levels

Charchar F , Tomaszewski M , Padmanabhan S , Lacka B , Anderson N , Zukowska-Szczechowska E , Grzeszczak W , Dominiczak A

Objective: To examine if there was an association between blood pressure and two polymorphic markers, M9 (CtoG) and HindIII in the non-recombining region of the Y chromosome.Design and Methods: 204 pedigrees all including hypertensive individuals were collected from the south of Poland after local Ethical committee approval. Phenotypic data including hypertensive status as well as BP, weight and height were collected. We phenotyped and genotyped 155 unr...