A common mutation of low-density lipoprotein receptor gene is associated with essential hypertension among Japanese

Candidate genes offer one approach to the identification of the genetic sus ceptibility to hypertension, A common gene variant of the low-density lipop rotein (LDL) receptor gene (LDLR) that affects plasma LDL metabolism within the normolipidaemic range, may be such a candidate gene, A common mutation of LDLR, C1773T, was associated with lipid metabolism such that the T1773 allele increased plasma LDL levels in a Caucasian population. The present s tudy examined whether C1773T/LDLR was associated with essential hypertensio n in a Japanese population. Subjects with essential hypertension (EHT, n = 300) with a family history of hypertension, and controls (NT, n = 310, sex- and age-matched with EHT) were recruited from among outpatients at Osaka U niversity Hospital. A C1773T substitution at codon 570 in LDLR was determin ed using PCR- Hinc II-RFLP. It was revealed that the C1773 allele was signi ficantly more frequent (0.89) among hypertensive patients (X-2 = 9.58, P < 0.01) than normotensives (0.83), the calculated odds ratio being 1.7 (95% C I: 1.2-2.4). The effect of the T1773 allele on increasing cholesterol was s ignificant in normotensives without antihyperlipidaemic medication, but not in hypertensives. After adjustments of confounding factors, the estimated odds ratio for hypertension in the subjects with C1773 homozygote increased to 2.1 (95% CI: 1.3-3.5), suggesting that this polymorphism is an independ ent risk factor for hypertension. Our results show that the C1773 mutant of LDLR increases susceptibility to hypertension, but not via hypercholestero laemia.