SIGNIFICANT RELATIONSHIPS OF PLASMA-LIPIDS AND BODY-MASS INDEX WITH POLYMORPHISMS AT THE LINKED LOW-DENSITY-LIPOPROTEIN RECEPTOR GENE AND INSULIN-RECEPTOR GENE LOCI (19P13.2) IN ESSENTIAL HYPERTENSIVE PATIENTS

1. Recent molecular genetic studies have implicated the low-density-li poprotein receptor gene locus (LDLR, at chromosome 19p13.2) in obesity in essential hypertensive patients and in the atherogenic lipoprotein phenotype. The present study examined genotypes for the obesity-assoc iated ApaLI restriction fragment length polymorphism of LDLR, and geno types for a hypertension-associated RsaI restriction fragment length p olymorphism at the insulin receptor gene (INSR) locus, which is linked to LDLR, in relation to plasma lipids, body mass index and blood pres sure in 27 obese and 57 non-obese Caucasians with severe essential hyp ertension, selected on the basis of having parents who were both hyper tensive, and in 25 obese and 45 non-obese normotensive subjects select ed on the basis of having parents who were both normotensive after the age of 50 years. 2. Plasma triacylglycerol and low-density-lipoprotei n-cholesterol were elevated in hypertensive patients, but did not diff er between the obese and non-obese hypertensive groups. Significant po sitive correlations were seen between body mass index and triacylglyce rol and low-density-lipoprotein-cholesterol in the obese and non-obese hypertensive patients, respectively. In addition, obese hypertensive patients had significantly higher diastolic blood pressure than nonobe se hypertensive patients. 3. The eight obese hypertensive patients who were homozygous for the obesity-associated 6.6 kb allele of the ApaLI restriction fragment length polymorphism of LDLR ('6.6. kb homozygote s') had a significantly higher body mass index [34 +/- 6.0 (SD) kg/m(2 )] than the 18 heterozygotes (29 +/- 2.7 kg/m(2)) and the single subje ct who was homozygous for the 9.4 kb allele (29 kg/m(2)) (P = 0.012 by one-way analysis of variance). The body mass index of the eight hyper tensive 6.6 kb homozygotes was also greater than the body mass index o f 29 +/- 2.4 kg/m(2) observed for the eight obese normotensive 6.6 kb homozygotes. In addition, the eight obese hypertensive 6.6 kb homozygo tes had a higher plasma triacylglycerol [4.2 +/- 0.77 (SEM) mmol/l] th an the 18 obese hypertensive heterozygotes (2.4 +/- 0.33 mmol/l; P = 0 .045). Non-obese hypertensive patients showed no significant gentotypi c differences in relation to the LDLR restriction fragment length poly morphism. 4. In the normotensive group, however, the frequency of the 6.6 kb allele of the LDLR ApaLI restriction fragment length polymorphi sm in obese subjects (0.54) was not significantly greater than in non- obese subjects (0.48) [cf. the significantly (P = 0.004) different val ues of 0.63 and 0.39, respectively, in obese and non-obese hypertensiv e patients]. Moreover, the LDLR genotype showed no significant relatio nship to the body mass index or plasma lipids in the obese and non-obe se normotensive groups. 5. In the case of genotypes for the INSR restr iction fragment length polymorphism, the only difference was slightly higher total and low-density-lipoprotein-cholesterol in non-obese hype rtensive patients who possessed the hypertension-associated 7.0 kb all ele. 6. Comparison of combined genotypes for LDLR and INSR restriction fragment length polymorphisms in hypertensive patients indicated that each associated independently in the various groups.