Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Recent molecular genetic studies have implicated the low-density-lipoprotein 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-associated ApaLI restriction fragment length polymorphism of LDLR, and genotypes for a hypertension-associated RsaI restriction fragment length polymorphism at the insulin receptor gene (INSR) locus, which is linked to LDLR, in relation to plasma lipids, body mass index and blood pressure in 27 obese and 57 non-obese Caucasians with severe essential hypertension, selected on the basis of having parents who were both hypertensive, and in 25 obese and 45 non-obese normotensive subjects selected on the basis of having parents who were both normotensive after the age of 50 years. 2. Plasma triacylglycerol and low-density-lipoprotein-cholesterol were elevated in hypertensive patients, but did not differ between the obese and non-obese hypertensive groups. Significant positive correlations were seen between body mass index and triacylglycerol 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 non-obese 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 homozygotes') had a significantly higher body mass index [34 +/- 6.0 (SD) kg/m2] than the 18 heterozygotes (29 +/- 2.7 kg/m2) and the single subject who was homozygous for the 9.4 kb allele (29 kg/m2) (P = 0.012 by one-way analysis of variance). The body mass index of the eight hypertensive 6.6 kb homozygotes was also greater than the body mass index of 29 +/- 2.4 kg/m2 observed for the eight obese normotensive 6.6 kb homozygotes. In addition, the eight obese hypertensive 6.6 kb homozygotes had a higher plasma triacylglycerol [4.2 +/- 0.77 (SEM) mmol/l] than the 18 obese hypertensive heterozygotes (2.4 +/- 0.33 mmol/l; P = 0.045). Non-obese hypertensive patients showed no significant genotypic differences in relation to the LDLR restriction fragment length polymorphism. 4. In the normotensive group, however, the frequency of the 6.6 kb allele of the LDLR ApaLI restriction fragment length polymorphism in obese subjects (0.54) was not significantly greater than in non-obese subjects (0.48) [cf. the significantly (P = 0.004( different values of 0.63 and 0.39, respectively, in obese and non-obese hypertensive patients.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID: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. 803 1

This paper provides a broad overview of the epidemiological and genetical aspects of common multifactorial diseases in man with focus on three well-studied ones, namely, coronary heart disease (CHD), essential hypertension (EHYT) and diabetes mellitus (DM). In contrast to mendelian diseases, for which a mutant gene either in the heterozygous or homozygous condition is generally sufficient to cause disease, for most multifactorial diseases, the concepts of genetic susceptibility' and risk factors' are more appropriate. For these diseases, genetic susceptibility is heterogeneous. The well-studied diseases such as CHD permit one to conceptualize the complex relationships between genotype and phenotype for chronic multifactorial diseases in general, namely that allelic variations in genes, through their products interacting with environmental factors, contribute to the quantitative variability of biological risk factor traits and thus ultimately to disease outcome. Two types of such allelic variations can be distinguished, namely those in genes whose mutant alleles have (i) small to moderate effects on the risk factor trait, are common in the population (polymorphic alleles) and therefore contribute substantially to the variability of biological risk factor traits and (ii) profound effects, are rare in the population and therefore contribute far less to the variability of biological risk factor traits. For all the three diseases considered in this review, a positive family history is a strong risk factor. CHD is one of the major contributors to mortality in most industrialized countries. Evidence from epidemiological studies, clinical correlations, genetic hyperlipidaemias etc., indicate that lipids play a key role in the pathogenesis of CHD. The known lipid-related risk factors include: high levels of low density lipoprotein cholesterol, low levels of high density lipoprotein cholesterol, high apoB levels (the major protein fraction of the low density lipoprotein particles) and elevated levels of Lp(a) lipoprotein. Among the risk factors which are not related to lipids are: high levels of homocysteine, low activity of paraoxonase and possibly also elevated plasma fibrinogen levels. In addition to the above, hypertension, diabetes and obesity (which themselves have genetic determinants) are important risk factors for CHD. Among the environmental risk factors are: high dietary fat intake, smoking, stress, lack of exercise etc. About 60% of the variability of the plasma cholesterol is genetic in origin. While a few genes have been identified whose mutant alleles have large effects on this trait (e.g., LDLR, familial defective apoB-100), variability in cholesterol levels among individuals in most families is influenced by allelic variation in many genes (polymorphisms) as well as environmental exposures. A proportion of this variation can be accounted for by two alleles of the apoE locus that increase (ε4) and decrease (ε2) cholesterol levels, respectively. A polymorphism at the apoB gene (XbaI) also has similar effects, but is probably not mediated through lipids. High density lipoprotein cholesterol levels are genetically influenced and are related to apoA1 and hepatic lipase (LIPC) gene functions. Mutations in the apoA1 gene are rare and there are data which suggest a role of allelic variation at or linked LIPC gene in high density lipoprotein cholesterol levels. Polymorphism at the apoA1--C3 loci is often associated with hypertriglyceridemia. The apo(a) gene which codes for Lp(a) is highly polymorphic, each allele determining a specific number of multiple tandem repeats of a unique coding sequence known as Kringle 4. The size of the gene correlates with the size of the Lp(a) protein. The smaller the size of the Lp(a) protein, the higher are the Lp(a) levels. (ABSTRACT TRUNCATED)
 ...
PMID:Ionizing radiation and genetic risks. VI. Chronic multifactorial diseases: a review of epidemiological and genetical aspects of coronary heart disease, essential hypertension and diabetes mellitus. 987 81

Candidate genes offer one approach to the identification of the genetic susceptibility to hypertension. A common gene variant of the low-density lipoprotein (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 study examined whether C1773T/LDLR was associated with essential hypertension 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 out-patients at Osaka University Hospital. A C1773T substitution at codon 570 in LDLR was determined using PCR-Hinc II-RFLP. It was revealed that the C1773 allele was significantly more frequent (0.89) among hypertensive patients (chi2 = 9.58, P < 0.01) than normotensives (0.83), the calculated odds ratio being 1.7 (95% CI: 1.2-2.4). The effect of the T1773 allele on increasing cholesterol was significant 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 independent risk factor for hypertension. Our results show that the C1773 mutant of LDLR increases susceptibility to hypertension, but not via hypercholesterolaemia.
 ...
PMID:A common mutation of low-density lipoprotein receptor gene is associated with essential hypertension among Japanese. 1131 92

Hypertension and dyslipidemia exhibit an important clinical relationship because an increase in blood lipids yields an increase in blood pressure (BP). We analyzed the associations of seven polymorphisms of genes involved in lipid metabolism (APOA5 rs3135506, APOB rs1042031, FABP2 rs1799883, LDLR rs5925, LIPC rs1800588, LPL rs328, and MTTP rs1800591) with blood pressure and lipid values in Mexican hypertensive (HT) patients. A total of 160 HT patients and 160 normotensive individuals were included. Genotyping was performed through PCR-RFLP, PCR-AIRS, and sequencing. The results showed significant associations in the HT group and HT subgroups classified as normolipemic and hyperlipemic. The alleles FABP2 p.55T, LIPC -514T, and MTTP -493T were associated with elevated systolic BP. Five alleles were associated with lipids. LPL p.474X and FABP2 p.55T were associated with decreased total cholesterol and LDL-C, respectively; APOA5 p.19W with increased HDL-C; APOA5 p.19W and FABP2 p.55T with increased triglycerides; and APOB p.4181K and LDLR c.1959T with decreased triglycerides. The APOB p.E4181K polymorphism increases the risk for HT (OR = 1.85, 95% CI: 1.17-2.93; P = 0.001) under the dominant model. These findings indicate that polymorphisms of lipid metabolism genes modify systolic BP and lipid levels and may be important in the development of essential hypertension and dyslipidemia in Mexican HT patients.
...
PMID:Association of polymorphisms of genes involved in lipid metabolism with blood pressure and lipid values in mexican hypertensive individuals. 2558 5