Effects of a nine-month occupational intervention on health-related quality of life.

The aim of this study was to evaluate the effectiveness of vocationally outpatient oriented rehabilitation on an intervention group, compared with a control group that did not take part in the intervention. The groups were compared for health-related quality of life (HRQoL) by the quantitative indicator RAND 36. Data were obtained by a self-report at baseline and at nine months follow-up. Differences between base-line and follow-up were analyzed within group and between the groups. The study population consisted of 751 municipal employees aged between 26 and 64 years; an intervention with 463 women and 115 men ( n = 578), and a control group with 138 women and 35 men ( n = 173). In this study we focused on those who had answered to all questions in RAND 36, thus 581 remained. Of these, 388 were in the intervention group (mean age 49.0 years) and 110 in the control group (mean age 48.4 years). Intervention was based on cognitive behavioral therapy. Participants in the 9-month outpatient intervention group showed statistically significant increase in all eight RAND 36 areas. Most improvement was seen in the psychosocial functioning index ( p = 0.002). Although there were no statistically significant changes in RAND 36 components in the control group, difference in changes between groups were seen in energy and fatigue ( p < 0.001), social functioning ( p = 0.032) and general health perceptions 0.027 in favor of the intervention group. The results suggest that a cognitive behavioral intervention as an early rehabilitation program is effective in increasing employees' quality of life, as measured by RAND 36.

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.

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.

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.

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.

Food allergy in small children carries a risk of essential fatty acid deficiency, as detected by elevated serum mead acid proportion of total fatty acids.

BACKGROUND: Elevated serum Mead acid as a proportion of total fatty acids is an indirect marker of a deficiency of essential fatty acids (EFA). The aim of the study was to evaluate the symptoms and nutrition of food-allergic children with elevated or normal serum Mead acid. METHODS: Serum fatty acid compositions from 400 children were studied by clinical indications, mostly by suspicion of deficiency of EFA due to inadequate nutrition. A Mead acid level exceeding 0.21% (percentage of total fatty acids) was considered to be a specific sign of an insufficient EFA supply. From a total of 31 children with elevated Mead acid (MEADplus group), 23 (74%) had food allergy. The symptoms and dietary restrictions of this MEADplus group of food allergic children were compared to 54 age-and sex-matched controls with food allergy but normal Mead acid proportions (MEADminus group) before and 6 months after the serum fatty acid determination. RESULTS: At the beginning of the 6-month follow-up, 44% of the food allergic children in both MEADplus and MEADminus groups were on an elimination diet. These diets did not differ between the two groups and we were not able to document an association between the severity of elimination diet and elevated Mead acid proportion. However, the MEADplus children were on average more symptomatic than MEADminus children. In the MEADplus group, food allergy presented with skin symptoms in 100% (vs. 70% in the MEADminus group, p < 0.001) and with vomiting or diarrhea in 70% (vs. 44% in the MEADminus group, p < 0.05). Clinical suspicion of malnutrition resulted in increase in the use of vegetable oil and milk-free margarine in both groups from <50% to 65-74% during the follow-up. After 6 months, 64% of the MEADplus children with food allergy had been sent to a control serum fatty acid analysis. Of these children, Mead acid had declined to normal level in 69%, and remained elevated in 31%. CONCLUSIONS: Severe symptoms of food allergy combined with elimination diets in children may lead to insufficient nutrition presenting with elevated serum Mead acid. Adding of supplementary polyunsaturated fat to the diet should be considered in these children.

Contribution of SLC7A1 genetic variant to hypertension, the TAMRISK study.

BACKGROUND: The rs41318021 polymorphism in the SLC7A1 gene affects endothelial NO production through changes in L-arginine transport. This variation could thus hypothetically cause dysfunction of endothelium and lead to hypertension. The association of rs41318021 with hypertension was therefore studied in a Finnish cohort. METHODS: A total of 412 hypertensive cases and 771 non-hypertensive controls from a Finnish 50-year-old cohort were included in this study. The data was collected from the Tampere adult population cardiovascular risk study (TAMRISK). DNA was extracted from buccal swabs and amplified using PCR. A subpopulation of men and women who had available follow-up data of blood pressure measurements at the age of 35-, 40-, 45- and 50 years was also analyzed. RESULTS: There was no difference between the variant frequencies of the hypertension group and normotensive group at the age of 50 years (p = 0.209). However, repeated measures analysis from the 15-year follow-up showed that subjects having gene variants CT or TT had slightly higher diastolic blood pressure than subjects having genotype CC (p = 0.047). By post-hoc analysis, this was most pronounced at the age of 35 years (p = 0.044). CONCLUSION: The rs41318021 polymorphism in the SLC7A1 gene was not associated with essential hypertension in 50-year-old subjects. However, a borderline effect of this variation upon diastolic blood pressure was seen in these same subjects in a 15-year follow-up from a 35-year-old cohort to 50 years of age.

Delta-6-desaturase gene polymorphism is associated with lipoprotein oxidation in vitro.

BACKGROUND: Oxidative modification of low-density lipoprotein (LDL) is a key event in the oxidation hypothesis of atherogenesis. We have previously shown that HDL does not protect LDL from oxidation in vitro, but is in fact oxidized fastest of all lipoproteins due to its rich polyunsaturated fatty acid (PUFA) composition, which is oxidation promoting. Evidence has accumulated to show that in addition to diet, common polymorphisms in the fatty acid desaturase (FADS) gene cluster have very marked effects on human PUFA status. There is a deletion [T/-] in the promoter region of the Δ6 -desaturase gene (FADS2, rs 3834458), which has a direct inhibitory influence on production of PUFA from linoleic and alpha-linolenic acid. To investigate the possible role of rs 3834458 in lipoprotein modification, oxidation of LDL with HDL2 or HDL3 were analyzed from plasma of 58 free-living individuals. RESULTS: Total eicosapentaenoic acid and arachidonic acid were significantly decreased in plasma from the 10 subjects homozygous for the deletion in FADS2 rs 3834458. When the isolated LDL and HDL2 were subjected to Cu²âº-induced oxidation, these subjects showed decreased rate of appearance (p = 0.027) and the final concentration of conjugated dienes (p = 0.033) compared to the other genotypes. For oxidation of LDL with HDL3, the final concentration of conjugated dienes was also significantly decreased in subjects with [-/-] compared with [T/T] and [T/-] (p = 0.034). CONCLUSION: We conclude that FADS2 genotype may play a role in peroxidation susceptibility of lipoproteins.

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.

No association of nineteen COX-2 gene variants to preclinical markers of atherosclerosis The Cardiovascular Risk in Young Finns Study.

BACKGROUND: The role of cyclooxygenase-2 (COX-2) single nucleotide polymorphisms has mostly been studied in relation to advanced atherosclerosis, but little is known how they contribute to preclinical disease. In the present study we analyzed whether COX-2 gene variants associate independently with the early subclinical markers of atherosclerosis, carotid intima-media thickness and carotid artery distensibility in a population of young healthy Caucasian adults. METHODS: SNPs for association analysis were collected from the COX-2 gene and 5 kb up- and downstream of it. There were 19 SNPs available for analysis, four genotyped and fifteen imputed. Genotype data was available for 2442 individuals participating in the Cardiovascular Risk in Young Finns Study. Genotype imputation was performed using MACH 1.0 and HapMap II CEU (release 22) samples as reference. Association analysis was performed using linear regression with an additive model. PLINK was used for true genotyped SNPs and ProbABEL for imputed genotype dosages. False discovery rate was used to take into account multiple testing bias. RESULTS: Two of the COX-2 variants (rs689470, rs689462) associated with distensibility (p = 0.005) under the linear regression additive model. After adjustment with gender, age, body mass index and smoking status, association between these SNPs and distensibility remained significant (p = 0.031). Subjects carrying the minor alleles had higher value of carotid artery distensibility compared to the major allele homozygotes. However, after correcting p-values for multiple testing bias using false discovery rate, association was lost. Another COX-2 variant rs4648261 associated with mean carotid intima-media thickness (p = 0.046) and maximal carotid intima-media thickness (p = 0.048) in the linear regression model. Subjects carrying the minor allele of rs4648261 had lower values of mean and maximal carotid intima-media thickness compared to subjects homozygote for major allele. After adjustments the associations were lost with both mean and maximal carotid intima-media thickness. Thus, no statistically significant associations of the studied COX-2 variants with carotid artery distensibility or carotid intima-media thickness were found. CONCLUSIONS: Our results suggest that in a Finnish population, there are no significant associations between COX-2 variants and early atherosclerotic changes in young adulthood.

Periodic cohort health examinations in the TAMRISK study show untoward increases in body mass index and blood pressure during 15 years of follow-up.

BACKGROUND: Obesity is a significant risk factor for hypertension and diabetes. A cohort of 50-year-old voluntary periodic health examination (PHE) participants was analyzed 15 years retrospectively. Our aim was to evaluate changes in body mass index (BMI) and blood pressure in subjects diagnosed with hypertension and/or diabetes in comparison with healthy controls. METHODS: Voluntary periodic health examinations (PHE) of the citizens have been carried out by the city of Tampere, Finland. Health data, including body mass index (BMI) and blood pressure, were recorded every five years, starting at the age of 35 (baseline). A total of 339 subjects from the 50-year-old cohort having hypertension and/or diabetes were chosen to the study group. The control group included 604 subjects from the 50-year-old cohort who had the same follow-up information but were not diagnosed with hypertension and/or diabetes. RESULTS: In the study group the mean BMI had increased from 26.1 at baseline to 28.5 at the final 15-year follow-up examination. The corresponding increase in the control group was from 23.8 at baseline to 25.5 at the final follow-up. The difference in change with time between the groups was statistically significant (p = 0.04). On the average, the controls gained 4.9 kilograms, whereas subjects in the study group gained 7.0 kilograms over the 15 years of follow-up. Systolic and diastolic blood pressures were also higher in the study group already at baseline and systolic blood pressure increased with time more in the study group than in the control group (p = 0.004). CONCLUSIONS: BMI and blood pressure were higher in the study group in comparison with the controls already at baseline at 35 years, and the differences were not favorably changed during the follow-up. Apparently, the effect of PHE had not been as efficient as planned on subjects in the study group, who were already slightly overweight at baseline.

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.

Late-life coronary heart disease mortality of Finnish war veterans in the TAMRISK study, a 28-year follow-up.

BACKGROUND: Wartime stress has been associated with increased late-life mortality of all causes of death. We evaluated whether wounded Finnish World War II veterans who were alive at the age of 55 have increased long-term coronary heart disease (CHD) mortality. METHODS: Health survey data were recorded in 1980 from 667 men, aged 55 years. Of them 102 had been wounded or injured in action during 1939-1945. The remaining participants served as the comparison group. The death certificates during a 28-year follow-up were obtained from the national statistics centre. Statistical comparisons were done by Cox proportional hazard regression model. RESULTS: There were altogether 140 deaths from CHD. In men who had been wounded or injured in action the crude CHD mortality rate per 10,000 population was 2843, while in the comparison group the corresponding figure was 1961. Men who had been wounded or injured in action were 1.7 times (95% CI 1.1-2.5; p = 0.01) more likely to die from CHD than the comparison group. CONCLUSIONS: Physical trauma at young adulthood may extend to lifelong effects on health. This study suggests that being physically wounded or injured in war may lead to increased CHD mortality in late adulthood in a Finnish population.

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.

Hematocrit and the risk of coronary heart disease mortality in the TAMRISK study, a 28-year follow-up.

OBJECTIVE: To evaluate whether hematocrit (HCT) is associated with coronary heart disease (CHD) mortality in men over 55 years of age in Finland. METHODS: Health survey data were recorded in 1980 from 670 men, aged 55 years. The causes of deaths during a 28-year follow-up were obtained from official records. Statistical comparisons were done by Cox proportional hazard regression model after dividing the men into two groups, one with HCT<50% and the other, HCT> or =50%. RESULTS: There were altogether 412 deaths of all causes, including 140 from CHD. In men having HCT<50%, the crude CHD mortality rate per 10,000 population was 2203, while in men with HCT> or =50%, the corresponding figure was 4255. Men with HCT> or =50% were 2.4 times (95% CI 1.6-3.5) more likely to die from CHD than were men with HCT<50%. After adjusting for established coronary risk factors, the increased risk remained 1.8-fold (95 % CI, 1.1-2.7). CONCLUSIONS: Borderline polycythemia was associated with increased CHD mortality. The cut-off value in our study was > or =50%, proposing that for men over 55 years of age such HCT levels might be an additional risk factor.

Arachidonic acid increases matrix metalloproteinase 9 secretion and expression in human monocytic MonoMac 6 cells.

BACKGROUND: Dietary fatty acids may modulate inflammation in macrophages of the atherosclerotic plaque, affecting its stability. The n-6 polyunsaturated fatty acid (PUFA) arachidonic acid (AA) generally promotes inflammation, while the PUFAs of the n-3 series eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) are considered anti-inflammatory. We determined how these PUFAs influence MMP-9 expression and secretion by the human monocytic cell line (MonoMac 6) at baseline and after 24-hour exposure. MMP-9 protein was measured by zymography and relative levels of MMP-9 mRNA were determined using quantitative real time PCR. RESULTS: Supplementation with AA (but not the n-3 fatty acids) increased, in a dose-dependent manner, expression of MMP-9 protein. This stimulation was regulated at the mRNA level. MMP-9 secretion started after 1 h of incubation and could not be prevented by simultaneous presence of n-3 series fatty acids. Finally, the secretion could be attenuated by LY 294002, a specific phosphatidylinositol-3-kinase (PI3K) inhibitor and by SH-5, a selective Akt inhibitor, suggesting that activation of PI3K by AA leads to augmented and sustained MMP-9 production. CONCLUSION: This study shows that of the PUFA studied, AA alone influences the expression of MMP-9, which might have implications in MMP-9 induced plaque rupture.

Gln27Glu variant of Beta2-adrenoceptor gene affects male type fat accumulation in women.

BACKGROUND: The beta2-adrenergic receptor (BAR2) is the main lipolytic receptor in white human adipose tissue. There is a functional glutamine 27 glutamic acid (Gln27Glu, rs 1042714) polymorphism in its gene, which has been variably associated with body mass index. This gene variant may be associated with male-type adiposity in women and thus increased cardiovascular risk. We investigated whether the BAR2 Gln27Glu polymorphism is associated with visceral fat and coronary intima thickness in women. METHODS: The amount of mesenteric and omental fat was directly measured and anthropometric measurements were done from 112 forensic autopsy cases of women aged 15 to 49 years. The thickness of the coronary intima, which reflects the severity of atherosclerosis, was measured by computerized image analysis. The BAR2 Gln27Glu polymorphism was determined by polymerase chain reaction. RESULTS: We found that the amount of visceral fat was significantly higher in women with the Glu allele (689 +/- 555 g) compared to Gln/Gln homozygotes (481 +/- 392 g, P = 0.023). The waist-hip ratio also tended to be higher in women with the Glu allele compared to Gln/Gln homozygotes (p = 0.050). There were no statistically significant differences between the genotype groups in BMI or the thickness of coronary intima. CONCLUSION: The Glu allele of the BAR2 gene may be a risk factor for visceral fat accumulation in young to middle-aged women. However, this polymorphism was not associated with preclinical atherosclerosis.