Endocrine Abstracts (2004) 7 P227

No association of a polymorphism in the kozak sequence of the CD40 gene and Graves' disease in a UK Caucasian population

H Foxall1, JM Heward1, JA Franklyn1 & SC Gough1,2


1Department of Medicine, University of Birmingham, Birmingham, UK; 2Birmingham Heartlands Hospital, Bordesley Green East, Birmingham, UK.


Graves' disease (GD) is an autoimmune disease of the thyroid gland with unknown aetiology thought to be caused by a complex interaction between genetic and environmental factors. To date, the HLA region on chromosome 6p21 and the CTLA-4 gene on chromosome 2q33 are thought to account for about 50% of the genetic component of GD with the remaining genetic contribution likely to be made up of many genes each exerting a small effect on predisposition to disease. A recent study (Tomer et al; 2002) identified a single nucleotide polymorphism (SNP) in the Kozak sequence at position -1 of the CD40 gene which leads to a C to T change. Case control analysis showed the CC genotype of this SNP to be associated with GD in a small Caucasian cohort (n = 272). The aim of the current study was to replicate this result in a larger dataset of 960 patients with GD and 864 control subjects of UK Caucasian origin. Samples were amplified using the polymerase chain reaction and the resulting amplicon was subjected to restriction fragment length polymorphism using the enzyme StyI under appropriate conditions. The resulting products were resolved on a 3% agarose gel. Statistical analysis of allele and genotype frequencies between cases and control subjects were performed using MINITAB and p<0.05 was considered to be significant. No differences were observed between cases and control subjects at either the allele (chi-squared = 2.94; p = 0.087, 1 degree of freedom) or genotype (chi-squared = 3.86; p = 0.145, 2 degrees of freedom) levels despite having 99.9% power to detect an effect of this polymorphism if present, at an odds ratio of 1.5 and p = 0.05. In conclusion, this particular polymorphism of the CD40 gene does not appear to influence genetic susceptibility to GD in the UK.

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