Hematocrit value at early middle age predicts hypertension at late middle age; the Tampere adult population cardiovascular risk study, a 30-year follow-up.

A 50-year-old cohort from the Tampere adult population cardiovascular risk study having hypertension and their controls were examined retrospectively at the age of 35 years, and followed up prospectively up to the age of 65 years to determine whether an early hematocrit (HCR) measurement predicts later hypertension or cardiovascular complications. A total of 307 subjects having hypertension and 579 non-hypertensive controls were chosen from the 50-year-old cohort and regrouped according to HCR values obtained when they were 35 years old, one with HCT < 45 % (n = 581), and the other, with HCT ≥ 45 % (n = 305). Hypertension and coronary artery disease (CAD) by the age of 60 years were determined by self-report and the National Hospital Discharge Registry. Outcomes for death up to the age of 65 years were collected from the National Statistics Centre. HCT ≥ 45 % at the age of 35 years associated with hypertension (p = 0.041) and CAD (P = 0.047) by the age of 60 years. When the subjects were followed up to the age of 65 years, HCT ≥ 45 % associated with premature cardiovascular death (P = 0.029), and death by any cause (P = 0.004). These results were obtained after adjusting for BMI-class recorded at 50 years of age. However, when outcome was also adjusted by gender, current smoking, vocational education, and state of one's health, association of the ≥ 45 % group with CAD and death was abolished. The association with hypertension remained (P = 0.007). In conclusion, there was a significant association of HCT ≥ 45 % at early middle age with subsequent hypertension.

The gene variant for desmin rs1058261 may protect against combined cancer and cardiovascular death, the Tampere adult population cardiovascular risk study.

Desmin-containing intermediate filaments are a part of muscle cytoskeleton. We have previously reported that the wild-type cytosine/cytosine genotype of a common Desmin synonymous single nucleotide polymorphism (C > T) (rs1058261) associated with cardiovascular diseases in a cohort of subjects from the Tampere adult population cardiovascular risk study. We now examined whether rs1058261 also associates with early death by following the cohort of 801 subjects from the age of 50 up to the age of 65. Outcomes for death were collected from the National Statistics Centre. Linkage disequilibrium analysis and gene expression correlations for rs1058261 were done in silico. With follow-up, subjects with wild-type cytosine/cytosine genotype had higher incidence of cancer deaths (odds ratio [OR] 5.27, confidence interval [CI] 1.160-23.946, P = .031), combined deaths from cardiovascular diseases or cancers (OR 3.92, CI 1.453-10.596, P = .007), and "hard" acute cardiovascular disease events (early myocardial infarction and/or death) (OR 3.90, CI 1.287-11.855, P = .016) compared to subjects with the T-allele. The in silico results of linkage disequilibrium and gene expression analyses showed negative gene expression sizes associated with rs1058261, which theoretically decreases desmin expression. Our findings suggest that variation rs1058261 in Desmin may serve as a surrogate marker for other variations involved in decrease of deaths from combined cancer and cardiovascular disease.

Hepcidin is potential regulator for renin activity.

An association between genetic variants in the genes HFE, HJV, BMP4 and arterial hypertension has been shown earlier. Proteins encoded by these genes participate in the signalling routes leading eventually to the production of the peptide hormone hepcidin. Mutations in these genes have been associated with the abnormal production of hepcidin in the body. This finding led to studies exploring the possible role of hepcidin in regulating the activity of blood pressure related renin-angiotensin system enzymes. We used molecular modelling to find out if it is possible for hepcidin to bind to the active site of the renin-angiotensin system enzymes, especially renin. Fluorometric assays were used to evaluate the inhibitory effect of hepcidin on renin as well as angiotensin converting enzymes 1 and 2. Finally, bio-layer interferometry technique was used to study hepcidin binding to renin. The molecular modelling showed that hepcidin seems to have similar binding properties to the renin active site as angiotensinogen does. Based on fluorometric enzyme activity assay, hepcidin has an inhibitory effect on renin in vitro, too. However, angiotensin converting enzymes 1 and 2 were not inhibited remarkably by hepcidin-25. In bio-layer interferometry analysis hepcidin-renin binding was concentration dependent. Our results suggest that hepcidin could act as an inhibitor to the renin. Nowadays, there is no known biological inhibitor for renin in vivo and our finding may thus have important clinical implications.

Association of Desmin Gene Variant rs1058261 with Cardiovascular Disease, the TAMRISK Study.

AIMS: Since desmin expression is diminished in vascular smooth muscle cells during reparative processes, we wanted to study whether a common intragenic single nucleotide polymorphism at nucleotide position 828 (rs1058261) of the DES gene associates with hypertension, cerebrovascular complications, and all cardiovascular events in the Tampere adult population cardiovascular risk (TAMRISK) study. MATERIALS AND METHODS: A Finnish periodic health examination cohort of 336 subjects with diagnosed hypertension and 473 controls were analyzed. Samples were genotyped for polymorphism using TaqMan techniques. Prevalence of ischemic heart diseases, incidence of cerebrovascular diseases, and transient cerebral ischemic attacks (TIAs) were obtained by self-report and the National Hospital Discharge Registry (HILMO). RESULTS: There was no association of any of the rs1058261 genotypes with hypertension at the age of 50. When the subjects were followed to the age of 60, after adjustment for gender and body mass index, subjects with the genotype CC had higher incidence of cerebrovascular events (cerebrovascular diseases and TIA) (4.1%) compared with the T allele (1.6%) (p = 0.046). In addition, those with CC genotype had a higher incidence of all combined cardiovascular events (12.8%) compared with subjects with the T allele (8.5%) (p = 0.028). CONCLUSIONS: Our findings suggest that variations in the DES gene may be involved in cardiovascular disease.

Association of a Chromosome Locus 9p21.3 CDKN2B-AS1 Variant rs4977574 with Hypertension: The TAMRISK Study.

AIMS: Chromosome locus 9p21.3 CDKN2B antisense RNA 1 (CDKN2B-AS1) has been found to contain multiple genetic markers for coronary artery disease (CAD) by genome-wide association studies (GWAS). Of these, the association of variants rs4977574, rs10757274, and rs2383206 with hypertension was studied in the Tampere adult population cardiovascular risk study (TAMRISK). MATERIALS AND METHODS: A Finnish cohort of 336 subjects diagnosed with hypertension and 444 controls was analyzed. Samples were genotyped for the CDKN2B-AS1 polymorphisms using Kompetitive Allele Specific PCR (KASP) or TaqMan techniques. RESULTS: Individuals with the minor genotype GG of rs4977574 had less hypertension compared to the other genotypes (p = 0.048, OR 1.58, 95% CI 1.01-2.48). The variants rs2383206 and rs10757274 were not associated with hypertension. CONCLUSIONS: Our findings suggest that the GG genotype of the CDKN2B-AS1 gene variant rs4977574, which has been previously associated with an increased CAD risk, is also associated with a decreased susceptibility to the development of hypertension.

Genetic variation in bone morphogenetic proteins family members (BMPs 2 and 4) and hypertension risk in middle-aged men: The TAMRISK study.

Bone morphogenetic proteins (BMPs) are important regulators of iron metabolism affecting hepcidin expression. We have previously shown that 2 genetic polymorphisms in different genes (histocompatibility complex class I-like transmembrane protein, hemojuvelin) involved in the regulation of hepcidin expression pathways are associated with hypertension. In this study, we analyzed genetic variation sites in BMP2 (rs235756, rs235768) and BMP4 (rs4901474) to get more evidence linking iron metabolism to hypertension risk in the Finnish population.The study included 321 hypertensive cases and 463 controls from the Tampere Adult Population Cardiovascular Risk study cohort. Genotyping of polymorphisms was done by polymerase chain reaction using DNAs extracted from buccal swabs.We found that men carrying the GG genotype of BMP2 rs235756 (A>G) polymorphic site had a 4.09-fold risk (confidence interval [CI] 1.61-10.39, P = .003) for hypertension at the age of 50 years compared with A-allele carriers. The risk was significant in the age groups of 45 and 40 years as well. In addition, the 15-year follow-up period of the same individuals showed that carriers of the GG-genotype had also significantly higher readings of both systolic (P < .001) and diastolic (P = .01) blood pressure during the follow-up time. No significant association between BMP2 rs235768 (A>T) and hypertension was found. BMP4 polymorphic site rs4901474 (T>C) also had an effect on hypertension. CC genotype carriers had a 1.48-fold risk (CI 1.03-2.13, P = .033) for hypertension at the age of 50 years when compared with T-allele carriers.In conclusion, BMP2 polymorphic site rs235756 was associated with hypertension in Finnish men. An effect of BMP4 polymorphic site on hypertension was also found.