Ingrid Rietveld

Mortality from Creutzfeldt–Jakob disease and related disorders in Europe, Australia, and Canada

Background: An international study of the epidemiologic characteristics of Creutzfeldt–Jakob disease (CJD) was established in 1993 and included national registries in France, Germany, Italy, the Netherlands, Slovakia, and the United Kingdom. In 1997, the study was extended to Australia, Austria, Canada, Spain, and Switzerland. Methods: Data were pooled from all participating countries for the years 1993 to 2002 and included deaths from definite or probable CJD of all etiologic subtypes. Results: Four thousand four hundred forty-one cases were available for analysis and included 3,720 cases of sporadic CJD, 455 genetic cases, 138 iatrogenic cases, and 128 variant cases. The overall annual mortality rate between 1999 and 2002 was 1.67 per million for all cases and 1.39 per million for sporadic CJD. Mortality rates were similar in all countries. There was heterogeneity in the distribution of cases by etiologic subtype with an excess of genetic cases in Italy and Slovakia, of iatrogenic cases in France and the UK, and of variant CJD in the UK. Conclusions: This study has established overall epidemiologic characteristics for Creutzfeldt–Jakob disease (CJD) of all types in a multinational population–based study. Intercountry comparisons did not suggest any relative change in the characteristics of sporadic CJD in the United Kingdom, and the evidence in this study does not suggest the occurrence of a novel form of human bovine spongiform encephalopathy infection other than variant CJD. However, this remains a possibility, and countries currently unaffected by variant CJD may yet have cases.

A polymorphic CA repeat in the IGF-I gene is associated with gender-specific differences in body height, but has no effect on the secular trend in body height.

objective  A polymorphism near the promoter region of the IGF‐I gene has been associated with serum IGF‐I levels, age‐related decline of serum IGF‐I levels, body height, birth weight and intima media thickness in hypertensive subjects.

An IGF-I Gene Polymorphism Modifies the Risk of Diabetic Retinopathy

The role of IGF-I in the pathogenesis of diabetic retinopathy is unclear. We studied, prospectively, the relationship between an IGF-I gene polymorphism, retinal vessel diameters, and incident diabetic retinopathy in subjects with impaired glucose tolerance (IGT) or type 2 diabetes. In all 5,505 participants of the population-based Rotterdam Study (775 with IGT, 394 with type 2 diabetes, and 4,336 control subjects), fundus color transparencies were taken at baseline (between 1990 and 1993) and at follow-up (from 1997 to 1999). The wild-type genotype (i.e., carriers of the 192- or 194-bp alleles) was present in 72.7% of the participants, while 27.3% were variant carriers. Variant carriers with IGT or type 2 diabetes appeared to have larger retinal arteriolar and venular diameters at baseline than individuals with the wild-type genotype, but these differences did not reach statistical significance. This trend was especially observed in subjects who developed retinopathy at follow-up. In variant carriers with IGT/diabetes, an increase (odds ratio 1.8 [95% CI 1.0–3.2]; P = 0.04) in the risk of retinopathy was observed compared with participants with the wild-type genotype. In conclusion, our findings suggest that this IGF-I gene polymorphism is associated with an increased risk of diabetic retinopathy.

A polymorphic CA repeat in the promoter region of the insulin-like growth factor-I (IGF-I) gene

In this issue of EJEP, Kato et al. describe their genotype–phenotype analysis in a small study group comprising both Caucasian people and African– Americans. In their study group the most frequent allele of the polymorphism in the promoter region of the IGF-I gene contains 18 CA repeats in both ethnic groups and no homozygote carriers of the 19 CA repeat were found. In Whites the frequency of the 19 CA repeat was significantly higher compared to African Americans. No relation was found between the number of CA repeats and serum IGF-I levels among all the subjects combined or in the white or black subgroups separately. A positive relation was found between IGF-I levels and height and cigarette smoking, and as expected age tended to be inversely associated with serum IGF-I. Several points need to be addressed. One issue is the allele that is most frequently present in the study population. The IGF-I gene, which is located on chromosome 12q, contains in the promoter region a micro-satellite comprising a variable length of a CA repeat sequence. Length of the repeat sequence ranges from 10 to 24, with the most frequent allele containing 19 CA repeats in six previous studies all involving Caucasian people [1–6]. In a previous study in African–Americans only the most frequent allele contained 18 CA repeats [7]. This suggests that during evolution there has been a shift towards longer alleles.