Risk of Alzheimer's disease is associated with a very low-density lipoprotein receptor genotype in Northern Ireland

The epsilon-4 allele of apolipoprotein E (APOE) is associated with increase d risk of Alzheimer's disease (AD), but the pathogenic mechanism is unknown The 5-repeat allele of a CGG repeat: polymorphism in the 5' untranslated r egion of the very low-density lipoprotein receptor (VLDL-R) gene, a recepto r for apoE, has been found to be associated with increased risk of AD in a Japanese population. Other groups have been unable to replicate this in Ame rican Caucasian populations. A case-control study utilizing a clinically we ll-defined group of late-onset AD patients (n = 108) and age- and sex-match ed control subjects (n = 108) from Northern Ireland was performed to test t his association in a relatively homogeneous population, The 9,9 genotype of the VLDL-R was found to be significantly increased in patients compared to controls (P = 0.003; P-corr = 0.035), leading to an increased risk of AD t o subjects with this genotype (OR = 3.9; 95% CI, 1.52-11.25), In contrast t o results from the Japanese study, the 5-repeat allele was found to be sign ificantly reduced in the patient group when compared to controls (P = 0.008 ; P-corr = 0.047). The results from this study suggest that individuals who have the 9,9 genotype of the VLDL-R gene are at increased risk of AD in No rthern Ireland, (C) 1999 Wiley-Liss, Inc.