Family history of hypertension enhances age-dependent rise in blood pressure, a 15-year follow-up, the Tampere adult population cardiovascular risk study.

A family history (FH) of hypertension is known to predispose to high blood pressure. We wanted to study whether it associates with blood pressure and hypertension in the Tampere adult population cardiovascular risk 15-year longitudinal study. A 50-year-old Finnish cohort having hypertension and their controls was examined retrospectively. The groups were combined and stratified to 396 subjects with a positive FH of hypertension and 384 with a negative FH. A 15-year follow-up was done from their periodic health examinations at the ages of 35-, 40-, 45-, and 50 years. In follow-up from the age of 35 years, systolic blood pressure (P < .001), diastolic blood pressure (P < .001), and the annual increase of systolic blood pressure (P < .010) were higher in the group with positive FH, compared to the negative FH group. Positive FH associated with diagnosed hypertension by the age of 50 years (OR 3.52, P < .001). The FH groups were not associated with body mass index. Our findings show that the prevalence of hypertension at the age of 50 years was significantly higher in those with a positive FH of hypertension. Asking about FH can provide the clinician with a simple instrument for recognition of subjects at risk of hypertension for closer monitoring at a younger age.

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.

Variant rs6749447 (T > G) in the serine threonine kinase gene is associated with cardiovascular complications, the Tampere adult population cardiovascular risk study.

ABSTRACT: We have previously shown an association of STK39 (serine threonine kinase) rs6749447 (T > G) with hypertension in the Tampere adult population cardiovascular risk study in 50-year-old subjects. These 1196 subjects were followed up to the age of 65 years to determine whether rs6749447 is also associated with coronary artery disease (CAD), transient ischemic attack (TIA), or early cardiovascular death.DNA samples were collected by buccal swabs and genotypes were determined by PCR. Hypertension, TIA, and CAD were determined by questionnaire and the National Hospital Discharge Registry. Outcomes for death were collected from the National Statistics Centre. Linkage disequilibrium analysis and gene expression correlations for rs6749447 were done in silico.After following the subjects up to the age of 60 years the rs6749447 G-allele still associated with hypertension (P = .009). The variation did not associate with CAD (P = .959). The risk for TIA was 5.2-fold among G-allele carriers compared to TT genotype even after adjusting for body mass index (P = .036, 95% CI 1.11-24.59). After follow-up of the subjects to the age of 65 years, adjusting for body mass index, the G-allele was associated with 3.2-fold risk of premature cardiovascular death (P = .049, 95% CI 1.00-10.01).In conclusion, the STK39 genetic variant rs6749447 was significantly associated with TIA and premature cardiovascular death in a Finnish cohort. The in silico results of linkage disequilibrium and gene expression analyses also showed associations that were distinct from the retention of salt effect on kidneys proposed earlier for this intronic variation.

Positive Association of the JAG1 rs1327235 Genotype with Coronary Artery Disease in Men, the Tampere Adult Population Cardiovascular Risk Study.

Aims: The intronic single nucleotide polymorphism rs1327235 (A>G) close to the JAG gene has been implicated to be involved in blood pressure physiology in a genome-wide association study. We wanted to study whether it was associated with hypertension and coronary artery disease (CAD) in the Tampere adult population cardiovascular risk study. Materials and Methods: We analyzed a Finnish periodic health examination cohort of 191 men with diagnosed hypertension and 295 controls. Samples were genotyped for the JAG1 rs1327235 polymorphism using Competitive Allelic Specific PCR (KASP). The incidence of CAD was determined by self-report and the National Hospital Discharge Registry (HILMO). Results: There was no association between the JAG1 rs1327235 genotypes with hypertension at the age of 50 years. However, when the subjects were followed to the age of 60 years, those with the genotype GG had a higher prevalence of CAD (17.9%), compared with the A-allele (9.7%) (p = 0.036). When prevalence of CAD was adjusted by body mass index and total cholesterol, the OR for GG genotype was 2.19 (p = 0.029, confidence interval 1.084 - 4.429) compared with A-allele carriers. In addition, the GG genotype was associated with higher total cholesterol and low-density lipoprotein-cholesterol values, compared with the A-allele. Conclusions: Our findings suggest that the variations in JAG1 rs1327235 may be involved in CAD and cholesterol metabolism.

Association of the Collagen Type IV Alpha 1 Chain Gene rs3783107 GG Genotype with Hypertension, Asthma, and Eczema: The Tampere Adult Population Cardiovascular Risk Study.

Aims: Basement membranes (BMs) provide structural support to tissues, and also offer functional input to modulate cellular function. Type IV collagen is the most abundant protein in BMs. The collagen type IV alpha 1 chain (COL4A1) gene variant rs3783107 G > A has previously been associated with intracranial aneurysms. We examined this polymorphism's association with cerebrovascular events in the Tampere adult population cardiovascular risk study, and also evaluated its association with hypertension, asthma, and long-term eczema in this population. Materials and Methods: A Finnish periodic health examination (PHE) cohort of 331 subjects with diagnosed hypertension and 440 normotensive controls was analyzed. DNA was extracted from buccal swabs. Genotyping was performed using KASP (competitive allelic-specific amplification). Prevalence of hypertension, asthma, or long-term eczema was obtained from the PHE. The incidences of cerebrovascular diseases and transient cerebral ischemic attacks was obtained from the National Hospital Discharge Registry (HILMO). Results: Even after adjusting for body mass index class and gender, subjects with the rs3783107 major genotype GG had significantly more hypertension (OR [odds ratio] = 1.38, 95% CI [confidence interval]: 1.01-1.87, p = 0.043), asthma (OR = 2.78, 95% CI: 1.25-6.19, p = 0.012), and eczema (OR = 2.00, 95% CI: 1.08-3.70, p = 0.027) than those with the A allele. Furthermore, subjects with the GG genotype had significantly higher systolic (p = 0.026) and diastolic blood pressure (p = 0.013) that those with the A allele. Variant rs3783107 did not significantly associate with cerebrovascular events. Conclusions: Our findings suggest that there are genotype-phenotype associations between the COL4A1 gene variant rs3783107 and hypertension, asthma, and eczema.

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 low-density lipoprotein receptor-related protein 1 rs11613352 and angiopoietin-like 3 rs2131925 with hypertension in men-the Tampere adult population cardiovascular risk study.

BACKGROUND: We examined the association of three known genome-wide association study loci for blood lipids that have lead traits for triglycerides with hypertension in the Tampere adult population cardiovascular risk study. METHODS: A Finnish cohort of 190 men with diagnosed hypertension and 279 controls were analyzed. Samples were genotyped for low-density lipoprotein receptor-related protein 1 rs11613352 (C>T), angiopoietin-like 3 rs2131925 (T>G), and fatty acid desaturase 1 rs174546 (C>T) polymorphisms using competitive allele-specific polymerase chain reaction technique. RESULTS: At the age of 50, subjects with low-density lipoprotein receptor-related protein 1 rs11613352 (C>T) minor genotype TT had significantly more hypertension than those with the C allele (OR 5.17, CI 2.03-12.74, p < 0.001). Subjects with angiopoietin-like 3 rs2131925 (T>G) T allele had more hypertension than those with the minor genotype GG (OR 5.02, CI 1.40-17.98, p = 0.013). Fatty acid desaturase 1 rs174546 (C>T) did not associate with hypertension. CONCLUSION: Association of low-density lipoprotein receptor-related protein 1 rs11613352 and angiopoietin-like 3 rs2131925 with hypertension might imply a direct effect at the artery wall.

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.

Gene polymorphisms of fibronectin rs2289202 and fibrillin 2 rs331069 associate with vascular disease, the TAMRISK study.

Cell surface heparan sulfate (HS) proteoglycans interact with other extracellular matrix (ECM) components, and HS-binding regions are present in ECM proteins such as fibronectin and fibrillin. Because of their previously established role in susceptibility to intracranial aneurysms, the authors sought to determine whether polymorphisms of fibronectin (FN1, rs2289202) and fibrillin 2 (FBN2, rs331069) associate with selected cardiovascular risk factors and events in the TAMRISK study. A 50-year-old Finnish cohort of 810 subjects of whom 340 had diagnosed hypertension was analyzed. Samples were genotyped for FN1 rs2289202 and FBN2 rs331069 polymorphisms. Incidence of myocardial infarction (I21-I22), transient cerebral ischemic attacks (TIA, G45) and cerebrovascular diseases (I60-I69) were followed up until the subjects were on the average 60 years old. Subjects with FN1 rs2289202 (G>A) minor genotype AA had significantly more cerebrovascular disease than those with the G allele [P<0.001, odds ratio (OR), 8.73; confidence index (CI), 2.79-27.31], although those with the A allele had lower body mass index (P=0.008). Subjects with fibrillin rs331069 (T>C) minor genotype CC had more atherothrombotic disease (P=0.012, OR, 3.16; CI, 1.29-7.71), as measured by combined myocardial infarction and TIA, than those with the T allele. The gene polymorphisms for fibronectin and fibrillin 2 appear to associate with vascular disease.

Minor variant of rs 16827043 in the iron regulator hemojuvelin gene (HJV) contributes to hypertension: The TAMRISK study.

It is known that iron overload may lead to an increased risk for many diseases. According to GWAS studies, iron regulatory protein HFE gene variant H63D (rs1799945) was associated with hypertension, an observation which we were able to confirm also in our TAMRISK cohort. Thus, it is possible that abnormalities in iron homeostasis may predispose to hypertension. This prompted us to study whether there is an association between hypertension and another iron overload-associated gene, hemojuvelin (HJV), which has 2 common polymorphic sites (rs 16827043, rs7536827).The study included 336 hypertensive cases and 480 controls. All participants were 50- year-old Finnish men and women, and the data was collected from the Tampere adult population cardiovascular risk study (TAMRISK). Genotypes were determined using Competitive Allelic Specific PCR (KASP).We found that the minor variant of the HJV polymorphic site rs16827043 (G-allele) is a statistically significant factor associated with hypertension among 50 year-old individuals compared with the AA genotype carriers (OR = 1.66, 95% CI: 1.06 - 2.60, P = 0.03). The risk was even higher when overweight subjects (BMI>30) were excluded from the analyses. For the other polymorphic variant rs7536827, association with hypertension was found only among normal or slightly overweight A-allele carriers.In conclusion, HJV genetic variants were associated with essential hypertension in Finnish subjects from the TAMRISK cohort. Previous studies together with the present one indicate that individuals with possible dysregulation of iron metabolism may have higher risk for hypertension than those with normal iron homeostasis.

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.

Glucuronic Acid Epimerase (GLCE) Variant rs3865014 (A>G) Is Associated with BMI, Blood Hemoglobin, Hypertension, and Cerebrovascular Events, the TAMRISK Study.

Heparan sulfate proteoglycans modulate many physiological systems, and genes responsible for proteoglycan assembly and disassembly may affect their interaction. We sought to determine whether polymorphisms of the glucuronic acid epimerase (GLCE) rs3865014 and sulfatase-2 (SULF2) rs2281279, genes coding for enzymes participating in heparan sulfate side chain activity, associate with hypertension, selected cardiometabolic risk factors and cardiovascular events in the Tampere adult population cardiovascular risk study. A Finnish cohort of 339 subjects with diagnosed hypertension and 441 controls was analyzed. Samples were genotyped for GLCE rs3865014 (A>G) and SULF2 rs2281279 (T>C) polymorphisms using competitive allele-specific PCR (KASP) technique. Prevalence of ischemic heart diseases (I20-I25) and incidence of cerebrovascular diseases (I60-I69) and transient cerebral ischemic attacks (TIA) (G45) were followed up until the subjects were on the average 60 years old. GLCE rs3865014 G allele showed negative association with hypertension (p = 0.022), waist circumference (p = 0.032), BMI (p = 0.048), and positive association with hemoglobin (p = 0.029), low-density lipoprotein cholesterol (p = 0.031), and frequency of cerebrovascular events (p = 0.011). SULF2 rs2281279 showed no association with the studied parameters. The GLCE gene polymorphism rs3865014 appears to have biological relevance in human pathophysiology.

Decorin Genotypes, Serum Glucose, Heart Rate, and Cerebrovascular Events: The Tampere Adult Population Cardiovascular Risk Study.

BACKGROUND: Decorin is an extracellular matrix proteoglycan that may attenuate progression of atherosclerosis and its complications, such as stroke. Among its multitude of functions, decorin has been suggested to serve as a receptor for resistin, an adipokine involved in energy homeostasis. The GG genotype of the decorin polymorphism rs7308752 (A>G) and the CC genotype of the rs516115 (T>C) are associated with decreased plasma resistin levels. AIMS: The association of the above decorin genotypes with selected cardiometabolic risk factors and cerebrovascular events was studied in the Tampere adult population cardiovascular risk (TAMRISK) study. MATERIALS AND METHODS: A Finnish cohort of 336 subjects with diagnosed hypertension and 444 controls was analyzed. Samples were genotyped for decorin rs7308752 and rs516115 polymorphisms using a Competitive Allele-Specific PCR (KASP) technique. Cerebrovascular diseases (I60-I69), including transient cerebral ischemic attacks (G45), were followed up from 2005 to 2014. RESULTS: Subjects with either of decorin rs7308752 genotypes AG/GG had higher serum glucose (p = 0.015) and higher heart rate (p = 0.017) than those with AA genotype. Similarly, decorin rs516115 genotypes TC/CC were associated with higher serum glucose (p = 0.034) and higher frequency of cerebrovascular diseases (p = 0.015) compared to the TT genotype. However, decorin polymorphisms were not associated with hypertension or body mass index. CONCLUSIONS: These two decorin polymorphisms appear to have biological relevance in human vascular pathophysiology.

Genetic Polymorphisms of Transcription Factor NRF2 and of its Host Gene Sulfiredoxin (SRXN1) are Associated with Cerebrovascular Disease in a Finnish Cohort, the TAMRISK Study.

Oxidative stress is involved in the pathophysiology of many cardiovascular disorders, such as hypertension and atherosclerosis. NRF2 is the primary transcriptional regulator of several antioxidant genes, including that of sulfiredoxin (SRXN1). The association of genotypes of NRF2 and SRXN1 with cardiovascular conditions was studied in a Finnish cohort of 336 subjects with diagnosed hypertension and 480 normotensive controls from the Tampere adult population cardiovascular risk study (TAMRISK). Samples were genotyped for four SNPs (rs1962142, rs2706110, rs6721961 and rs6706649) in the NRF2 gene region and four SNPs (rs6053666, rs6116929, rs2008022, rs6085283) in the SRXN1 gene region using Competitive Allele Specific PCR (KASP) technique. Cardiovascular diseases were followed up from 2005 to 2014 using the Finnish National Hospital Discharge Registry (HILMO). Four out of eight studied polymorphisms: rs6721961, rs1962142, rs2706110 of NRF2, and rs6053666 of SRXN1 were associated with cerebrovascular disease. NRF2 polymorphism rs6721961 showed association with hypertension. NRF2 and SRXN1 polymorphisms, previously thought to be associated with human disease, appear to be associated particularly with cerebrovascular disease.

Functional Inducible Nitric Oxide Synthase Gene Variants Associate With Hypertension: A Case-Control Study in a Finnish Population-The TAMRISK Study.

Increased inducible nitric oxide synthase (iNOS) activity and expression has been associated with hypertension, but less is known whether the 2 known functional polymorphic sites in the iNOS gene (g.-1026 C/A (rs2779249), g.2087 G/A (rs2297518)) affect susceptibility to hypertension. The objective of this study was to investigate the association between the genetic variants of iNOS and diagnosed hypertension in a Finnish cohort.This study included 320 hypertensive cases and 439 healthy controls. All participants were 50-year-old men and women and the data were collected from the Tampere adult population cardiovascular risk study (TAMRISK). DNA was extracted from buccal swabs and iNOS single nucleotide polymorphisms (SNPs) were analyzed using KASP genotyping PCR. Data analysis was done by logistic regression.At the age of 50 years, the SNP rs2779249 (C/A) associated significantly with hypertension (P = 0.009); specifically, subjects carrying the A-allele had higher risk of hypertension compared to those carrying the CC genotype (OR = 1.47; CI = 1.08-2.01; P = 0.015). In addition, a 15-year follow-up period (35, 40, and 45 years) of the same individuals showed that carriers of the A-allele had more often hypertension in all of the studied age-groups. The highest risk for developing hypertension was obtained among 35-year-old subjects (odds ratio [OR] 3.83; confidence interval [CI] = 1.20-12.27; P = 0.024). Those carrying variant A had also significantly higher readings of both systolic (P = 0.047) and diastolic (P = 0.048) blood pressure during the follow-up. No significant associations between rs2297518 (G/A) variants alone and hypertension were found. However, haplotype analysis of rs2779249 and rs2297518 revealed that individuals having haplotype H3 which combines both A alleles (CA-GA, 19.7% of individuals) was more commonly found in the hypertensive group than in the normotensive group (OR = 2.01; CI = 1.29-3.12; P = 0.002).In conclusion, there was a significant association between iNOS genetic variant (rs2779249) and hypertension in the genetically homogenous Finnish population. Those who carried the rare A-allele of the gene had higher risk for hypertension already at the age of 35 years.

NLR family pyrin domain containing 3 (NLRP3) inflammasome gene polymorphism rs7512998 (C>T) predicts aging-related increase of blood pressure, the TAMRISK study.

BACKGROUND: The activation of NLR family pyrin domain containing 3 (NLRP3) inflammasome by cellular stress leads to activation of the inflammasome, and NLRP3 gene polymorphisms have been associated with autoinflammatory diseases. Inflammasomes have also been implicated in the initiation or progression of metabolic disorders such as atherosclerosis, type 2 diabetes and obesity. The association of NLRP3 genetic variant rs7512998 with blood pressure and hypertension was studied in a 50-year-old Finnish cohort with a subpopulation who had available data on blood pressure measurements also at the age of 45 years. RESULTS: NLRP3 gene polymorphism rs7512998 C-allele was associated with higher systolic (p = 0.006) and diastolic (p = 0.011) blood pressure compared to the TT-genotype carriers in 50-year-old subjects. In addition, by analysis of variance for repeated measures between ages of 45- and 50 years there was a significant time by genotype interaction; blood pressure increased more in subjects with the C-allele both in systolic (p = 0.035) and diastolic (p = 0.012) values. However, no association with diagnosed hypertension was found. CONCLUSION: We report for the first time that NLRP3 gene polymorphism rs7512998 was associated with systolic and diastolic blood pressure in 50-year-old subjects. In addition, an effect of this variation upon blood pressure was seen in these same subjects in a 5-year follow-up from a 45-year-old cohort to 50 years of age.

Association of Zinc Finger, C3HC-Type Containing 1 (ZC3HC1) rs11556924 Genetic Variant With Hypertension in a Finnish Population, the TAMRISK Study.

In a recent genome-wide association study, the zinc finger, C3HC-type containing 1 (ZC3HC1) polymorphism was strongly associated with coronary artery disease (CAD) by an unknown mechanism. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is related with CAD through low-density lipoprotein (LDL) metabolism. The association of both of the above genetic variants with hypertension was studied in a Finnish 50-year-old cohort.A total of 325 hypertensive cases and 444 nonhypertensive controls were obtained from the Tampere adult population cardiovascular risk study. Samples were genotyped for ZC3HC1 rs11556924 and PCSK9 rs11206510 polymorphisms using Competitive Allele Specific PCR technique. A subpopulation that had available follow-up data from ages of 40, 45, and 50 years was also analyzed.ZC3HC1 rs11556924 (C > T) genotype CC was associated with hypertension compared with the T-allele carriers (P = 0.013). PCSK9 rs11206510 (T > C) genotype was not associated with hypertension. Its major TT-genotype was associated with higher total cholesterol (P = 0.044) and LDL (P = 0.029) compared with the C-allele.We report for the first time that ZC3HC1 rs11556924 was associated with essential hypertension in 50-year-old patients. Although PCSK9 rs11206510 was not associated with hypertension, our study confirms its association with serum cholesterol levels.

Contribution of fatty acid transporter (CD36) genetic variant rs1761667 to body mass index, the TAMRISK study.

BACKGROUND: Human fatty acid transporter CD36 gene variations have previously been associated with fat preferences and obesity. These variations could thus cause overweight and hypothetically lead to hypertension. The association of CD36 SNP rs1761667 with body mass index (BMI) and hypertension was therefore studied in a Finnish cohort of adults. METHODS: The data were collected from the Tampere adult population cardiovascular risk study (TAMRISK). A total of 314 cases with diagnosed hypertension, and 422 non-hypertensive healthy controls were selected from a Finnish periodic 50-year-old health examination cohort. Most subjects had prior health examination data also from their 40- and 45-year examinations. DNA was extracted from buccal swabs and the human CD36 genetic variant was analyzed using KASP genotyping. RESULTS: The CD36 SNP rs1761667 variant AA was significantly associated with lower BMI, as compared to variants AG and GG at the ages of 40-, 45-, and 50 years (p < 0.001, p = 0.005 and p = 0.013, respectively). No association of this CD36 variation with hypertension was found. CONCLUSIONS: CD36 rs1761667 was associated with BMI in the TAMRISK study. Considering the multitude of roles of CD36 in processes related to fatty acid metabolism and sensing in the body, it is plausible that genetic variation in human fatty acid transporter CD36 can have effects on regulation of energy homeostasis.