Finnish Subjects Research Articles

Readiness to Change Profiles in Two Different Groups of Alcohol/Other Drug Abusers in the United States and Finland

ABSTRACT Information on alcohol/other drug abusers' readiness to change is needed for the individual planning of treatment. We investigated the readiness to change profiles of Finnish and North American alcohol/other drug abusers. The Finnish subjects (N = 780) were unselected alcoholics and polydrug users receiving inpatient treatment. The North American subjects (N = 946) were selected outpatient alcoholics treated on Project MATCH. Readiness to change was measured with the URICA (University of Rhode Island Change Assessment Scale). In the cluster analyses the subjects were placed in groups. The findings indicated that the readiness to change profiles of Americans and Finns are similar in form, but there were quantitative differences in grouping. The Finns' profiles were more often of the type resisting change compared to those of the Americans. These differences are most likely due to the fact that the Finnish subjects were unselected inpatients whereas the Americans were selected outpatients. The article considers the significance of the findings in the light of earlier profile studies and the treatment of alcohol/other drug abuse.

The Metabolic Syndrome Predicts Incident Stroke

Limited information is available on the role of the metabolic syndrome (MetS) to predict stroke. We investigated the relationship of the MetS and its single components, defined by 6 different criteria, with stroke in a prospective population-based study. The MetS was defined according to the World Health Organization, the European Group for the Study of Insulin Resistance, the National Cholesterol Education Program (NCEP), the American College of Endocrinology, the International Diabetes Federation, and the American Heart Association (updated NCEP) criteria. We investigated the relationship of the MetS with stroke using Cox regression analyses in 991 Finnish subjects without diabetes, aged 65 to 74 years at baseline, and followed-up for 14 years. The MetS defined by the World Health Organization, European Group for the Study of Insulin Resistance, NCEP, International Diabetes Federation, and updated NCEP criteria was significantly associated with incident stroke (fatal and nonfatal) when adjusted for confounding variables (HR, 1.52 to 1.72). After exclusion of subjects with myocardial infarction, these 5 definitions still predicted stroke (HR, 1.49 to 1.80). Of the single components of the MetS, the following predicted stroke in multivariable models when subjects with myocardial infarction were excluded: impaired glucose tolerance (2-hour glucose in an oral glucose tolerance test, 7.8 to 11.0 mmol/L) by the World Health Organization and American College of Endocrinology criteria (HR, 1.66); insulin resistance (HR, 1.60) by the European Group for the Study of Insulin Resistance criteria; and central obesity (HR, 1.52) by the NCEP criteria. The MetS defined by the 6 criteria except for the American College of Endocrinology definition predicts stroke in elderly subjects. However, impaired glucose tolerance alone is as strong a predictor of stroke as is the MetS defined by the World Health Organization, NCEP and updated NCEP criteria.

Diagnostic performance of plasma high sensitive C‐reactive protein in detecting three‐vessel coronary artery disease: modification by apolipoprotein E genotype

Objectives. Plasma high sensitive C‐reactive protein (hsCRP) concentration is an important clinical test of systemic inflammation and, like apoE ε4 allele, an important risk factor of coronary artery disease (CAD). We investigated whether the diagnostic performance of plasma hsCRP in detecting severe 3‐vessel CAD may be modified by apoE ε4 carrier status. Methods. The study population (Angiography and Genes Study) comprised 485 Finnish subjects (336 men and 149 women, mean age 64.0±1.0) undergoing coronary angiography. ApoE genotypes were determined by the PCR‐based method and by hsCRP using an automatic analyser. Results. The diagnostic performance of hsCRP concentration in distinguishing 3‐vessel CAD from its less widespread forms (non‐3‐vessel CAD) was assessed by receiver operating characteristic curve (ROC) analysis separately in apoE ε4 non‐carriers and ε4 carriers. ROC analysis showed that hsCRP predicted 3‐vessel CAD in apoE ε4 non‐carriers (AUC 0.646; SE 0.035; p = 0.0001; 95 % CI 0.578–0.714) but not in ε4 carriers (AUC 0.518; SE 0.049; p = 0.719; 95 % CI 0.422–0.615). Multinomial logistic regression analysis revealed a significant (p<0.05) apoE ε4 group versus hsCRP group (<1.0 mg/L/⩾1.0 mg/L) interaction in relation to incidence of 3‐vessel CAD. In apoE ε4 non‐carriers, high hsCRP (⩾1.0 mg/L) was significantly (OR 2.1; 95 % CI 1.233–3.562; p = 0.006) associated with high incidence of 3‐vessel CAD after adjustment for major CAD risk factors. Conclusion. The diagnostic performance of hsCRP in distinguishing 3‐vessel CAD from less extensive forms of coronary atherosclerosis is more accurate in a group of subjects without the apoE ε4 allele than in patients with it.

Psychoneurotic symptoms and alexithymia in coeliac disease

Objective. Depression, psychological problems and the impairment of quality of life are reported to occur in untreated coeliac disease. Alexithymia (“no words for feelings”) is associated with various gastrointestinal disorders. The aim of this study was to evaluate whether patients with coeliac disease suffer from psychoneurotic symptoms or alexithymia, and whether a gluten-free diet has an impact on the symptoms. Material and methods. The Crown-Crisp Experiential Index (CCEI) and its six subscales were applied to measure neurotic psychopathology, and the 20-item version of the Toronto Alexithymia Scale (TAS-20) and its 3-factor scales to measure alexithymia. The testing was carried out in 20 consecutive adult patients with biopsy-proven coeliac disease before and after one year of treatment on a gluten-free diet. The data were compared with those obtained earlier in non-coeliac Finnish subjects. Results. Somatic anxiety was higher in coeliac disease patients before the introduction of the gluten-free diet than after adhering to the diet. Otherwise, the diet had no significant impact on the CCEI scores. The patients were not suffering from alexithymia, but the TAS-20 score improved significantly during the follow-up. The scores did not differ from those published in the Finnish population. Conclusions. Psychological problems were not common in adult coeliac disease patients. Gluten-free diet had only a minor influence on the symptoms. Common knowledge about coeliac disease and the readily available gluten-free products may have had an impact on these results.

Single Nucleotide Polymorphisms of the MCHR1 Gene Do Not Affect Metabolism in Humans**

Melanin concentrating hormone receptor-1 (MCHR1) is a centrally and peripherally expressed receptor that regulates energy expenditure and appetite. Single nucleotide polymorphisms (SNPs) of the MCHR1 gene have been previously associated with obesity, but the results are inconsistent among different populations. This study was performed to determine whether SNPs of MCHR1 affect glucose and energy metabolism. We screened six SNPs of MCHR1 in a cross-sectional study of 217 middle-age, non-diabetic Finnish subjects who were offspring of type 2 diabetic patients. Insulin secretion was evaluated by an intravenous glucose tolerance test and insulin sensitivity and energy metabolism by the hyperinsulinemic euglycemic clamp and indirect calorimetry. SNPs of MCHR1 were not associated with BMI, waist circumference, subcutaneous or intra-abdominal fat area, glucose tolerance, first-phase insulin release, insulin sensitivity, or energy metabolism. One SNP, which was in >0.50 linkage disequilibrium with the other five SNPs, was also screened in 1455 unrelated Finnish middle-age subjects in a population-based study. No differences in BMI, waist circumference, or glucose or insulin levels in an oral glucose tolerance test among the genotypes were found. In conclusion, SNPs of MCHR1 did not have effects on metabolic variables in humans.

Occupational, Commuting, and Leisure-Time Physical Activity in Relation to Cardiovascular Mortality Among Finnish Subjects With Hypertension

The association between different types of physical activity and cardiovascular risk among hypertensive subjects is not fully understood. The purpose of this study was to determine the association of occupational, commuting, and leisure-time physical activity on cardiovascular mortality among hypertensive patients. Study cohorts included 26,643 hypertensive Finnish men and women who were aged 25 to 64 years and free of coronary heart disease, stroke, and Type 1 diabetes. During a mean follow-up of 19.9 years (range, 6.6 to 31.7 years), 3743 subjects died because of cardiovascular disease. The multivariate-adjusted (age, study year, education, alcohol consumption, smoking, body mass index, systolic blood pressure, total cholesterol, use of antihypertensive drugs, and diabetes at baseline or during follow-up, and the other two kinds of physical activity) hazard ratios of cardiovascular mortality associated with low, moderate, and high occupational physical activity were 1.00, 0.84, and 0.86 (P for trend = .006), respectively, for hypertensive men, and 1.00, 0.85, and 0.84 (P for trend = .014), respectively, for hypertensive women. The multivariate-adjusted hazard ratios of cardiovascular mortality associated with low, moderate, and high leisure-time physical activity were 1.00, 0.84, and 0.73 (P for trend < .001), respectively, for hypertensive men, and 1.00, 0.78, and 0.76 (P for trend < .001), respectively, for hypertensive women. Active commuting to and from work was significantly associated with reduced cardiovascular mortality in hypertensive women. Moderate or high levels of occupational or leisure-time physical activity reduce cardiovascular mortality among both men and women with hypertension. Walking or cycling to and from work daily reduces cardiovascular mortality among hypertensive women.

Joint effects of history of hypertension at baseline and type 2 diabetes at baseline and during follow-up on the risk of coronary heart disease

To evaluate the joint associations of history of hypertension at baseline and type 2 diabetes at baseline and during follow-up on the incidence of coronary heart disease (CHD) and CHD mortality. Study cohorts included 49 775 Finnish subjects aged 25-74 without history of CHD and stroke. The multivariable-adjusted hazard ratios (HRs) of CHD incidence were 1.25, 1.69, 1.25, 1.83, 1.85, 2.39, 2.15, and 3.31 (P-value for trend <0.001), respectively, among men with hypertension I (blood pressure 140-159/90-94 mmHg or using antihypertensive drugs at baseline but blood pressure <160/95 mmHg) only, with hypertension II (blood pressure > or =160/95 mmHg) only, with incident diabetes during follow-up only, with both hypertension I and incident diabetes, with both hypertension II and incident diabetes, with history of diabetes at baseline only, with both hypertension I and history of diabetes, and with both hypertension II and history of diabetes compared with men without either of these diseases. The corresponding HRs of CHD incidence among women were 1.52, 2.37, 2.45, 3.78, 4.56, 5.63, 6.10, and 7.41 (P-value for trend <0.001), respectively. The impact on CHD mortality associated with the different strata of hypertension and diabetes was almost the same or a little stronger compared with that on the CHD incidence. Hypertension and type 2 diabetes increase the CHD risk independently, and their combination increases the risk dramatically, particularly in women.

Somatostatin genetic variants modify the risk for Alzheimer's disease among Finnish patients

The levels of somatostatin are consistently decreased in the brain and cerebrospinal fluid of Alzheimer's disease (AD) patients. The somatostatin gene is located on chromosome 3q27.3 close to an association region identified in late-onset AD patients originating from Finland. Since somatostatin is a good candidate on both positional and functional grounds, we studied whether single nucleotide polymorphisms (SNPs) in the somatostatin gene were associated with AD in the Finnish population. We genotyped three SNPs within this gene in Finnish AD patients (n = 424) and non-demented controls (n = 466). AD patients were compared with non-demented control subjects using single-locus and haplotype approaches. In the whole study group, the age, sex and APOE adjusted OR for the risk of AD in C-allele carriers of the SNP rs4988 514 was 1.42 (p <0.05). Interestingly, in APOE epsilon4-allele carriers, the age and sex adjusted OR for the risk of AD in C-allele carriers of the rs4988 514 increased to 2.05 (p <0.01). Additionally, SNP rs4988514 may interact with the APOE epsilon4-allele to increase the risk of AD. Assessment of individual haplotype distributions revealed a 2-fold overrepresentation of the TCG haplotype of SNPs rs3864101, rs4988 514 and rs7624 906 in the AD APOE epsilon4-allele group (p <0.01). Conversely, a major haplotype TTG was significantly underrepresented among all the AD patients as well as APOE epsilon4-allele carrying AD patients. Thus the major haplotype TTG of somatostatin may have a protective effect against AD. This first genetic association study between somatostatin and AD indicates that genetic variations in the somatostatin gene may modify the risk for AD among Finnish AD subjects.

Sequence variation and linkage disequilibrium in the GABA transporter-1 gene (SLC6A1) in five populations: implications for pharmacogenetic research

BackgroundGABA transporter-1 (GAT-1; genetic locus SLC6A1) is emerging as a novel target for treatment of neuropsychiatric disorders. To understand how population differences might influence strategies for pharmacogenetic studies, we identified patterns of genetic variation and linkage disequilibrium (LD) in SLC6A1 in five populations representing three continental groups.ResultsWe resequenced 12.4 kb of SLC6A1, including the promoters, exons and flanking intronic regions in African-American, Thai, Hmong, Finnish, and European-American subjects (total n = 40). LD in SLC6A1 was examined by genotyping 16 SNPs in larger samples. Sixty-three variants were identified through resequencing. Common population-specific variants were found in African-Americans, including a novel 21-bp promoter region variable number tandem repeat (VNTR), but no such variants were found in any of the other populations studied. Low levels of LD and the absence of major LD blocks were characteristic of all five populations. African-Americans had the highest genetic diversity. European-Americans and Finns did not differ in genetic diversity or LD patterns. Although the Hmong had the highest level of LD, our results suggest that a strategy based on the use of tag SNPs would not translate to a major improvement in genotyping efficiency.ConclusionOwing to the low level of LD and presence of recombination hotspots, SLC6A1 may be an example of a problematic gene for association and haplotype tagging-based genetic studies. The 21-bp promoter region VNTR polymorphism is a putatively functional candidate allele for studies focusing on variation in GAT-1 function in the African-American population.

Developing the international distribution of humanities studies in Finland: the exchange of publications of two learned societies in 1831–1914

Examines the international exchange of publications of two Finnish learned societies: the Finnish Literature Society and the Finnish Antiquarian Society from their foundation until the outbreak of the First World War. The exchange of publications had two purposes: it was a means of acquiring international literature for the libraries of the societies and a way of distributing results of research to foreign scholars. In spite of the availability of texts written in the Finnish language and on Finnish subjects, the Finnish societies received many foreign exchange proposals. Relevancy of the received publications was usually not criticized and all the offers were accepted. These two societies trusted in the exchange as a means of distributing their studies internationally, and did not seriously endeavour to find commercial distribution channels for their publications.

Association of Kallikrein Gene Polymorphisms With Intracranial Aneurysms

Genomewide DNA linkage analysis identified a susceptibility locus for intracranial aneurysm (IA) on chromosome 19q13 in the Finnish population, a region including the kallikrein gene cluster. We investigated the association of single nucleotide polymorphisms (SNPs) in the kallikrein gene cluster with IA in the Finnish population. We genotyped 18 haplotype-tagging SNPs spanning a 244 kbp region in the kallikrein gene cluster for 266 Finnish IA cases and 290 Finnish control subjects. In a second phase, we genotyped 2 SNPs (rs1722561 and rs1701946) in an additional set of 102 Finnish IA cases and 102 Finnish control subjects; and in a third phase, we genotyped these 2 SNPs in 156 Russian IA cases and 186 Russian control subjects. Both single-marker and haplotype-based tests of association were performed. In phase I, SNPs rs1722561 and rs1701946 were significantly associated with IA in the Finnish population for single locus models (rs1722561: P=0.0395; rs1701946: P=0.0253). A 2-SNP haplotype block (rs1722561-rs1701946) identified in phase I was also associated with IA in the expanded Finnish (phase II) data set (asymptotic P=0.012; empirical P=0.019). In the Finnish and Russian combined data set (phase III) with 524 cases and 578 control subjects, the same 2 SNPs (OR: 1.35, 95% CI: 1.14, 1.60; P=0.0005 for rs1722561 and OR: 1.32, 95% CI: 1.12, 1.57; P=0.0011 for rs1701946) were significantly associated with IA. These SNPs are located in the intronic region of KLK8, although linkage disequilibrium could extend from rs268912-rs2250066, a approximately 76-kbp region that includes KLK5-KLK10. Polymorphisms within the kallikrein gene cluster are associated with IA suggesting that the kallikreins are important candidate genes for IA.

Coffee and tea consumption and the risk of Parkinson's disease

Several prospective studies have assessed the association between coffee consumption and Parkinson's disease (PD) risk, but the results are inconsistent. We examined the association of coffee and tea consumption with the risk of incident PD among 29,335 Finnish subjects aged 25 to 74 years without a history of PD at baseline. During a mean follow-up of 12.9 years, 102 men and 98 women developed an incident PD. The multivariate-adjusted (age, body mass index, systolic blood pressure, total cholesterol, education, leisure-time physical activity, smoking, alcohol and tea consumption, and history of diabetes) hazard ratios (HRs) of PD associated with the amount of coffee consumed daily (0, 1-4, and > or = 5 cups) were 1.00, 0.55, and 0.41 (P for trend = 0.063) in men, 1.00, 0.50, and 0.39 (P for trend = 0.073) in women, and 1.00, 0.53, and 0.40 (P for trend = 0.005) in men and women combined (adjusted also for sex), respectively. In both sexes combined, the multivariate-adjusted HRs of PD for subjects drinking > or = 3 cups of tea daily compared with tea nondrinkers was 0.41 (95% CI 0.20-0.83). These results suggest that coffee drinking is associated with a lower risk of PD. More tea drinking is associated with a lower risk of PD.

Coffee consumption and the incidence of antihypertensive drug treatment in Finnish men and women

Background: Only 2 prospective studies have previously investigated the association between coffee consumption and incident hypertension, and the findings are equivocal.Objective: The objective was to determine the relation between coffee consumption and the incidence of antihypertensive drug treatment.Design: We prospectively followed 24 710 Finnish subjects aged 25–64 y without a history of antihypertensive drug treatment, coronary heart disease, or stroke at baseline. Daily coffee consumption was assessed by questionnaires.Results: During a mean follow-up period of 13.2 y, 2505 participants started antihypertensive drug treatment. The multivariate-adjusted (age, sex, study year, education, leisure-time physical activity, smoking, body mass index, high total cholesterol, history of diabetes, and alcohol, tea, fruit, vegetable, sausage, and bread consumption) hazard ratios for antihypertensive drug treatment associated with the amount of coffee consumed daily (0–1, 2–3, 4–5, 6–7, or ≥8 cups) were 1.00, 1.29 (95% CI: 1.09, 1.54), 1.26 (95% CI: 1.06, 1.49), 1.24 (95% CI: 1.04, 1.48), and 1.14 (95% CI: 0.94, 1.37) (P for trend = 0.024), respectively. This trend became marginally significant after additional adjustment for baseline systolic blood pressure (P for trend = 0.077).Conclusions: The results indicate that coffee drinking seems to increase the risk of antihypertensive drug treatment, and this risk was higher in subjects with low-to-moderate coffee intakes; however, there was no significantly increased trend in drinkers of ≈1 cup (100 mL)/d or ≥8 cups/d.

Physical activity modifies the effect of SNPs in theSLC2A2(GLUT2) andABCC8(SUR1) genes on the risk of developing type 2 diabetes

Single nucleotide polymorphisms (SNPs) in two genes regulating insulin secretion, SLC2A2 (encoding GLUT2) and ABCC8 (encoding SUR1), were associated with the conversion from impaired glucose tolerance (IGT) to type 2 diabetes (T2D) in the Finnish Diabetes Prevention Study (DPS). We determined whether physical activity (PA), assessed annually with a questionnaire, modified the association of SNPs in SLC2A2 and ABCC8 with the conversion to T2D in the combined intervention and control groups of the DPS. Finnish overweight subjects with IGT (N = 479) were followed for an average of 4.1 yr. The interaction of the SNPs with the change in PA on the conversion to T2D was assessed using Cox regression with adjustments for the other components of the intervention (dietary changes, weight reduction). The carriers of the common homozygous genotype of rs5393, rs5394, or rs5404 of SLC2A2 and rs3758947 of ABCC8 who were in the lower third of the change in moderate-to-vigorous PA during the follow-up had a 2.6- to 3.7-fold increased risk of developing T2D compared with the upper third, whereas the rare allele carriers seemed to be unresponsive to changes in moderate-to-vigorous PA (for the interaction of genotype with change in PA, P = 0.022-0.027 for the SNPs in SLC2A2, and P = 0.007 for rs3758947). We conclude that moderate-to-vigorous PA may modify the risk of developing T2D associated with genes regulating insulin secretion (SLC2A2, ABCC8) in persons with IGT.

Measuring European Population Stratification with Microarray Genotype Data

A proper understanding of population genetic stratification--differences in individual ancestry within a population--is crucial in attempts to find genes for complex traits through association mapping. We report on genomewide typing of approximately 10,000 single-nucleotide polymorphisms in 297 individuals, to explore population structure in Europeans of known and unknown ancestry. The results reveal the presence of several significant axes of stratification, most prominently in a northern-southeastern trend, but also along an east-west axis. We also demonstrate the selection and application of EuroAIMs (European ancestry informative markers) for ancestry estimation and correction. The Coriell Caucasian and CEPH (Centre d'Etude du Polymorphisme Humain) Utah sample panels, often used as proxies for European populations, are found to reflect different subsets of the continent's ancestry.

Novel mutations in the small leucine-rich repeat protein/proteoglycan (SLRP) genes in high myopia

The importance of the genetic component in high myopia has been well established in population and family studies, but only a few candidate genes have been explored to date. The extracellular matrix small leucine-rich repeat proteins/proteoglycans (SLRPs) regulate collagen fibril diameter and spacing. Given their role in extracellular matrix assembly and expression in the eye, they are likely to regulate its shape and size. Analysis of 85 English and 40 Finnish subjects with high myopia (refractive error of -6 diopters [D] or greater) resulted in 23 sequence variations in four SLRP genes, LUM, FMOD, PRELP, and OPTC. We observed higher number of variations in OPTC in English patients than in controls (p=0.042), and a possibly protective variation in LUM (c.893-105G>A) with p-value of 0.0043. Two intronic variations, six nonsynonymous and one synonymous amino acid changes, were not found in any of the nonmyopic controls. Five changes were detected in opticin, Thr177Arg, Arg229His, Arg325Trp, Gly329Ser, and Arg330His, and all but one (Arg229His) were shown to cosegregate with high myopia in families with incomplete penetrance. A homology model for opticin revealed that Arg229His and Arg325Trp are likely to disrupt the protein structure, and PolyPhen analysis suggested that Thr177Arg, Arg325Trp, and Gly329Ser changes may be damaging. A Leu199Pro change in lumican and Gly147Asp and Arg324Thr variations in fibromodulin are located in the highly conserved leucine-rich repeat (LRR) domains. This study provides new insight into the genetics of high myopia, suggesting that sequence variations in the SLRP genes expressed in the eye may be among the genetic risk factors underlying the pathogenesis of high myopia.

Blood glucose and the metabolism of cholesterol in coronary patients with and without simvastatin treatment

Background and aim of the study Association of blood glucose with cholesterol metabolism and with cholesterol lowering during simvastatin treatment has not been studied earlier in hypercholesterolemic subjects with coronary heart disease. Methods Baseline blood glucose was compared with cholesterol synthesis (e.g. ratios of squalene and lathosterol) and absorption (e.g. sitosterol ratio) without and with simvastatin for one year in 806 non-diabetes Finnish subjects of the Scandinavian Simvastatin Survival Study. Results Baseline blood glucose was positively correlated with the baseline synthesis and negatively with the absorption of cholesterol, and positively with the synthesis/absorption ratio (e.g. p = 0.001 for lathosterol/sitosterol). Simvastatin decreased serum cholesterol by about 29% irrespective of glucose level, cholesterol synthesis by up to 34%, especially in the highest glucose quartile, and increased cholesterol absorption by up to 49%, especially in the lowest glucose quartile ( p < 0.01 for all). The one-year synthesis/absorption ratio was decreased proportionately to the baseline glucose, e.g. for lathosterol/sitosterol by over 40% ( p < 0.001) in different glucose quartiles ( p < 0.001 between quartiles). Conclusions Baseline blood glucose level is related positively to cholesterol synthesis and negatively to that of absorption. Despite a marked glucose-related decrease in cholesterol synthesis with simvastatin, serum cholesterol reduction was not dependent on the baseline glucose level.

Stronger symptoms of depression predict high coronary heart disease mortality in older men and women

Most cohort studies have found depressive symptoms to be associated with increased cardiovascular mortality in the elderly, but follow-up times have often been short and study populations small. To describe associations between stronger symptoms of depression and the risk of death from coronary heart disease (CHD) or myocardial infarction (MI) in elderly Finnish subjects free of CHD at the baseline. This study is a prospective population-based epidemiological and clinical twelve-year follow-up study in Lieto Health Centre, Finland. The basic population consisted of 1196 elderly (64 years of age or older) persons who lived in the municipality of Lieto in southwestern Finland in 1990. The occurrence of CHD was determined on the basis of electrocardiographic (ECG) findings, Rose questionnaire and the diagnoses in medical records. The persons with CHD were excluded from the study population. Symptoms of depression at the baseline were measured with the Zung Self-rating Depression Scale (ZSDS). Mortality was followed up for about 12 years. The Kaplan-Meier survival curves showed stronger symptoms of depression to be related to high risks of mortality from CHD or MI among men and women. According to the Cox model for men significant predictors for higher risk of CHD or MI mortality were stronger symptoms of depression, higher age and a large number of medications in use. When women were examined, significant predictors were stronger symptoms of depression and a large number of medications in use. Stronger symptoms of depression are an independent risk factor for high CHD or MI mortality in aged Finnish men and women free of CHD at baseline.

The A467T and W748S POLG substitutions are a rare cause of adult-onset ataxia in Europe

In a recent edition of Brain , Tzoulis and colleagues (Tzoulis et al ., 2006) described the presentation and natural history of neurological disease due to the c.1399G → A/A467T and c.2243G → C/W748S mutations in POLG. POLG codes for mitochondrial DNA (mtDNA) polymerase ( pol γ), the only polymerase present within mitochondria (Kaguni, 2004). Pathogenic POLG mutations were first described in autosomal dominant and recessive progressive external ophthalmoplegia (PEO) (Van Goethem et al ., 2001), and more recently in recessive late-onset ataxia with peripheral neuropathy (Van Goethem et al ., 2003; Winterthun et al ., 2005), and the Alpers–Huttenlocher syndrome (Naviaux and Nguyen, 2004; Davidzon et al ., 2005; Ferrari et al ., 2005). Hakonen et al . (2005) recently reported the high carrier frequency of the W748S POLG substitution in control subjects in Finland (1 : 125 controls), explaining the high prevalence of mitochondrial recessive ataxia syndrome (MIRAS) in Scandinavia. Haplotype analysis revealed a common POLG haplotype in Finnish, Norwegian, Belgian and British subjects carrying W748S, raising the possibility that the same substitution is a common cause of late-onset ataxia throughout Europe (Hakonen et al ., 2005). In Norway, c.1491G → C/Q497H and A467T have also been …

Resveratrol Improves Mitochondrial Function and Protects against Metabolic Disease by Activating SIRT1 and PGC-1α

Diminished mitochondrial oxidative phosphorylation and aerobic capacity are associated with reduced longevity. We tested whether resveratrol (RSV), which is known to extend lifespan, impacts mitochondrial function and metabolic homeostasis. Treatment of mice with RSV significantly increased their aerobic capacity, as evidenced by their increased running time and consumption of oxygen in muscle fibers. RSV's effects were associated with an induction of genes for oxidative phosphorylation and mitochondrial biogenesis and were largely explained by an RSV-mediated decrease in PGC-1alpha acetylation and an increase in PGC-1alpha activity. This mechanism is consistent with RSV being a known activator of the protein deacetylase, SIRT1, and by the lack of effect of RSV in SIRT1(-/-) MEFs. Importantly, RSV treatment protected mice against diet-induced-obesity and insulin resistance. These pharmacological effects of RSV combined with the association of three Sirt1 SNPs and energy homeostasis in Finnish subjects implicates SIRT1 as a key regulator of energy and metabolic homeostasis.