EFFECT OF THE STUI POLYMORPHISM IN THE LDL RECEPTOR GENE (ALA-370 TO THR) ON LIPID-LEVELS IN HEALTHY-INDIVIDUALS

We have examined the effect on plasma lipid levels of a single base ch ange in exon 8 of the LDL receptor gene that causes an amino acid chan ge Ala 370 to Thr in a sample of 318 Icelandic individuals selected at random from the general population. The change destroys a StuI restri ction site and was detected by digestion of pooled samples in groups o f 5. The frequency of the loss of the cutting site was 0.05 (95%CI=0.0 14-0.054). In men, those with the Thr allele (n=18) had 8.3% higher to tal cholesterol, 11.8% higher LDL cholesterol and 10.3% higher apolipo protein B than those with the common Ala allele, whereas in women thos e with the Thr allele (n=12) had levels lower by 7.4%, 13.3% and 10.1% respectively. These differences reached statistical significance only in the men (p<0.05). Functional analysis of CHO cells transfected wit h constructs of the LDL receptor cDNA carrying the Ala370 and Thr370 a lleles showed that within the limits of the assays there was no differ ence in function of the LDL receptor protein as measured by uptake and degradation of LDL. The data raise the possibility that amino acid su bstitutions that could affect LDL receptor function below the limits o f detection by conventional assays, may have an effect on plasma lipid levels in the general population.