Insulin receptor gene in hypertension.
The first molecular genetic association with human essential hypertension (HT) involved the insulin receptor gene (INSR). This highly significant result in Caucasians was for an insertion/deletion polymorphism in intron 9. A polymorphism in exon 8 showed a weak association, but a microsatellite in intron 2 proved negative for HT, although has shown an association with plasma insulin in Japanese. A similar spectrum of genetic associations for variants spanning INSR has been noted for insulin-dependent diabetic patients with rapidly-progressing renal disease, a subgroup having a strong family history of essential HT. Association with HT has also been found for an INSR variant in CHinese. Insulin resistance secondary to an INSR 'defect', or other causes, would increase insulin, which has cardiovascular effects, and insulin can raise angiotensinogen. Also, insulin is co-secreted with amylin, which can increase renin secretion. In the spontaneously HT rat there is evidence for reduced down-regulation of INSR expression in response to NaCl-loading, consistent with a promoter effect. When combined with observations of insulin resistance in essential HT patients and their pre-HT offspring, the possibility of dys-regulation of INSR merits attention in disease etiology in a proportion of essential HT patients.
Morris
B J
BJ
Department of Physiology, University of Sydney, NSW, Australia.
D017398:Alternative Splicing; D000682:Amyloid / Q000378:metabolism; D000808:Angiotensinogen / Q000378:metabolism; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000235:genetics / Q000378:metabolism; D018900:Dinucleotide Repeats; D005091:Exons; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism*; D007333:Insulin Resistance; D007438:Introns; D058228:Islet Amyloid Polypeptide; D011110:Polymorphism, Genetic; D051381:Rats; D011972:Receptor, Insulin / Q000235:genetics*
D000682:Amyloid; D005819:Genetic Markers; D058228:Islet Amyloid Polypeptide; D000808:Angiotensinogen; D011972:Receptor, Insulin