Apolipoprotein E is a genetic risk factor for fetal iodine deficiency disorder in China

Fetal iodine deficiency disorder (FIDD) is the principal form of endemic cr etinism, and the most common cause of preventable mental deficiency in the world. However not everyone at risk develops FIDD and familial aggregation is common. This suggests that genetic factors may also be involved. The Apo lipoprotein E (APOE) gene encodes for a lipoprotein that possesses a thyroi d hormone binding domain, and APOE genotype may affect the efficiency with which thyroid hormone influences neuronal cell growth during the first and second trimesters of fetal development. We have compared ApoE genotypes in 91 FIDD cases with 154 local control subjects, recruited from three iodine deficiency areas in central China. We have also genotyped 42 FIDD family ca ses and 158 normal individuals from the families of local controls, and 375 population controls from Shanghai, APOE epsilon 4 genotypes were significa ntly enriched in FIDD probands from each of the three iodine deficiency are as; the epsilon 4 allele frequency was 16% vs 6% in controls. The same effe ct was also observed when we compared FIDD family cases with controls and c ontrol families. Our data suggest that in iodine-deficient areas, the APOE epsilon 4 allele is a genetic risk factor for FIDD, The phenomenon may affe ct population selection and contribute to the low frequency of the epsilon 4 allele in Chinese compared to Caucasian populations.