B. J. Morris

EXAMINATION OF THE ROLE OF NITRIC OXIDE SYNTHASE AND RENAL KALLIKREIN AS CANDIDATE GENES FOR ESSENTIAL HYPERTENSION

1. Nitric oxide synthase and renal kallikrein are both involved in blood pressure regulation. Genes for these enzymes may, therefore, be considered candidates for hypertension pathogenesis.

HYPOTHESIS: GLUCAGON RECEPTOR GLYCINE TO SERINE MISSENSE MUTATION CONTRIBUTES TO ONE IN 20 CASES OF ESSENTIAL HYPERTENSION*

1. A missense mutation leading to reduced ligand affinity in the glucagon receptor (GCG‐R) has been found recently to be five‐fold more common in essential hypertensives than normotensives. The present paper provides additional information on patients that harbour this variant and proposes a possible mechanism by which this may lead to hypertension.

Association of a low density lipoprotein receptor microsatellite variant with obesity.

OBJECTIVE: To determine whether a microsatellite polymorphism located towards the 3’ end of the low density lipoprotein receptor gene (LDLR) is associated with obesity. DESIGN: A cross-sectional case-control study. SUBJECTS: One hundred and seven obese individuals, defined as a body mass index (BMI)≥26 kg/m2, and 163 lean individuals, defined as a BMI<26 kg/m2. MEASUREMENTS: BMI, blood pressure, serum lipids, alleles of LDLR microsatellite (106 bp, 108 bp and 112 bp). RESULTS: There was a significant association between variants of the LDLR microsatellite and obesity, in the overall tested population, due to a contributing effect in females (χ2=12.3, P=0.002), but not in males (χ2=0.3, P=0.87). In females, individuals with the 106 bp allele were more likely to be lean, while individuals with the 112 bp and/or 108 bp alleles tended to be obese. CONCLUSIONS: These results suggest that in females, LDLR may play a role in the development of obesity.

A LINKAGE AND CROSS-SECTIONAL STUDY OF HYPERTENSION AND OBESITY USING A POLY(A) Alu-REPEAT POLYMORPHISM AT THE GLUCAGON RECEPTOR GENE LOCUS (17q25)

1. Previous glucagon receptor gene (GCGR) studies have shown a Gly40Ser mutation to be more prevalent in essential hypertension and to affect glucagon binding affinity to its receptor. An Alu‐repeat poly(A) polymorphism colocalized to GCGR was used in the present study to test for association and linkage in hypertension as well as association in obesity development.

EVOLUTION OF RENIN

1. New gene data for three aspartyl proteases (human renin, mouse renin and human pepsin) permitted closer analysis of the gene duplication and fusion hypothesis for the evolution of this family of enzymes.