BACKGROUND:The Westergren method is the golden standard for measuring erythrocyte sedimentation rate (ESR). All ESR methods should agree with the standardized method of the International Council for Standardization in Hematology (ICSH). Citrate samples are commonly used for ESR. This extra sample adds costs and can be inconvenient for the patient. Therefore, some new automated ESR analyzers use EDTA samples, which are available for other hematology measurements.METHODS:We compared ESR measurements with StaRRsed Auto-Compact instrument to the ICSH standardized Westergren method in 200 patient samples.RESULTS:The correlation between methods was fairly good (R(2) = 0.72, y = 1.066x 0.24). However, with ESR results over 11 mm/h there were 55 subjects with a difference of over 30% between methods.CONCLUSIONS:This may have led to different treatment suggestions in 25 cases according to age- and gender-dependent normal values. The difference may be caused by two different anticoagulants used, different measuring times and the correlation equation used. The StaRRsed ESR method should be in better agreement with the Westergren method, which is the golden standard. ESR results have notable impact on patient diagnosis and follow-up.KEYWORDS:ESR; Erythrocyte sedimentation rate; StaRRsed; Westergren method.

The effects of the serotonin receptor 2A (HTR2A) and 1A (HTR1A) polymorphisms and maternal caregiving attitudes on child's later hostile attitudes were examined. The sample consisted of 819 Finnish children and adolescents. Nurturance was reported by the mothers during childhood, while hostile attitudes were reported by the participants in adulthood. Caregiving attitudes predicted hostile attitudes (β = −.069, p = .047), but HTR2A and HTR1A were not related to them. HTR2A rs6313 moderated the effect of caregiving on hostility. Among the carriers of T/T and T/C genotype, caregiving predicted hostility (β = −.26, p = .024 and β = −.18, p = .001, respectively), while no association among C/C carriers was observed. T allele carriers were sensitive to the effects of caregiving on hostility although this association dropped when controlling for depressive symptoms.

The relative contribution of genetic risk factors to the progression of subclinical atherosclerosis is poorly understood. It is likely that multiple variants are implicated in the development of atherosclerosis, but the subtle genotypic and phenotypic differences are beyond the reach of the conventional case-control designs and the statistical significance testing procedures being used in most association studies. Our objective here was to investigate whether an alternative approach—in which common disorders are treated as quantitative phenotypes that are continuously distributed over a population—can reveal predictive insights into the early atherosclerosis, as assessed using ultrasound imaging-based quantitative measurement of carotid artery intima-media thickness (IMT). Using our population-based follow-up study of atherosclerosis precursors as a basis for sampling subjects with gradually increasing IMT levels, we searched for such subsets of genetic variants and their interactions that are the most predictive of the various risk classes, rather than using exclusively those variants meeting a stringent level of statistical significance. The area under the receiver operating characteristic curve (AUC) was used to evaluate the predictive value of the variants, and cross-validation was used to assess how well the predictive models will generalize to other subsets of subjects. By means of our predictive modeling framework with machine learning-based SNP selection, we could improve the prediction of the extreme classes of atherosclerosis risk and progression over a 6-year period (average AUC 0.844 and 0.761), compared to that of using conventional cardiovascular risk factors alone (average AUC 0.741 and 0.629), or when combined with the statistically significant variants (average AUC 0.762 and 0.651). The predictive accuracy remained relatively high in an independent validation set of subjects (average decrease of 0.043). These results demonstrate that the modeling framework can utilize the “gray zone” of genetic variation in the classification of subjects with different degrees of risk of developing atherosclerosis.

Previous evidence suggests that the lactase gene C/T− 13910 polymorphism (rs4988235) is associated with avoidance of milk products and lower Ca intake. We examined whether the consumption of milk and milk products and the intakes of milk nutrients differ between the lactase genotypes from childhood to young adulthood. Subjects belong to the Cardiovascular Risk in Young Finns Study where the first cross-sectional surveys were conducted in 1980 (n 3596), with follow-up studies in 1983, 1986, 1989, 1992 and 2001 (n 2620). The same dietary questionnaire was used throughout the follow-up to collect data on habitual consumption of milk and milk products in all subjects, and daily nutrient intakes were assessed with 48 h dietary recalls in 50 % of the subjects. Subjects with the lactase non-persistence (C/C− 13910) genotype consumed less milk since childhood, but the consumption of other milk products did not differ between the genotypes. In adult females, the lactose content of milk products consumed was lower (P = 0·003), and in both sexes low-lactose and milk-free diets were more common in the C/C− 13910 genotype than in the other genotypes. Inadequate Ca intake was most common in females with the C/C− 13910 genotype as early as in childhood (15–63 %), but in males only in adulthood (24 %). In adult females, preference for low-lactose milk and milk products equalised the differences in Ca intake between the genotypes. Thus, in those with the C/C− 13910 genotype, preference for low-lactose milk and milk products may decrease the risk for inadequate Ca intake.

The association of two tryptophan hydroxylase 2 (TPH2) polymorphisms and treatment response in electroconvulsive therapy (ECT) and the risk of depression was studied. The patient sample consisted of 119 subjects with treatment-resistant major depressive disorder who were treated with ECT. Treatment response was assessed by the Montgomery and Åsberg Depression Rating Scale (MADRS) scores. Patients who had <8 scores in post-treatment MADRS were considered remitters; scores >15 indicated non-response. The polymorphisms studied (rs1386494 and rs1843809) were not associated with treatment response to ECT. However, TPH2 rs1386494 A/A genotype carrying patients had significantly higher MADRS scores before ECT than A/G + G/G genotype carriers (p < 0.001). A/A genotype carriers also had a greater decline in MADRS scores than A/G + G/G genotype carriers during the course of ECT treatment (p = 0.03). This polymorphism may be associated with the severity of treatment-resistant depression. ECT may able to counteract a putative genetically driven worse depressive phenotype.

Intrauterine exposure to SSRIs in late pregnancy can cause various serotonergic symptoms in the newborns. We associated the severity of these symptoms to neurotransmitter concentrations and genetic polymorphisms in the cytochrome P450, MAO-A and COMT enzymes. Altogether 20 children with prenatal exposure to citalopram or fluoxetine were genotyped. Infants with two high-activity alleles of the MAO-A gene had significantly higher serotonergic symptom scores than infants with at least one low-activity allele (mean 8.8 vs. 2.4, p = 0.024). These infants had also higher cord blood DHPG concentrations (p = 0.0054). Carriers of the high-activity COMT alleles had higher cord blood prolactin concentrations (p = 0.044). According to our results, the higher serotonergic symptom score and cord blood DHPG concentration in rapid MAO-A metabolizers suggest that norepinephrine may modify the severity of perinatal serotonergic symptoms. The COMT 1947G > A polymorphism may affect the occurrence of respiratory distress symptoms in infants with prenatal SSRI-exposure via a mechanism involving prolactin.

We studied the association between RGS4 (rs951436) polymorphism and treatment response in electroconvulsive therapy (ECT) as well as risk of treatment-resistant depression. The study sample consisted of 119 patients with major depressive disorder (MDD) and 384 healthy control subjects. RGS4 polymorphism was not associated with treatment response in ECT or risk of MDD. According to the present data, the impact of RGS4 genotype is not decisive in major depressive disorder. The results provide preliminary data on the impact of RGS4 polymorphism in treatment response in ECT.

Objective: The increased plasma concentrations of pro-atherogenic and cardiomyocyte hypertrophic cytokine interleukin 18 (IL-18) predict mortality inpatients with coronary heart disease (CHD) in addition to predicting the outcome of heart failure. The IL-18 gene has a functional -137 G/C polymorphism (rs187238) in the promoter region. The C allele carriage is associated with attenuated IL-18 production. The effect of IL-18 genotype on SCD is unknown. We studied the association of the IL-18 gene -137 G/C polymorphism with the occurrence of sudden cardiac death (SCD).Methods: Using the TaqMan 5' nuclease assay, we genotyped two independent consecutive and prospective autopsy series which were included in the Helsinki Sudden Death Study.Results: Of the 663 men, 359 (54.1%) had the wild-type GG-genotype, 261 (39.4%) were heterozygotes (CG) and 43 (6.5%) were CC homozygotes. Compared to the GG homozygotes, the C allele carriers (i.e. subjects having CC or CG genotypes) had a lower adjusted risk for SCD from any cause (odds ratio [OR] 0.49; 95% confidence interval [CI], 0.31-0.77, p =0.002), for SCD due to CHD (OR 0.51; 95% CI, 0.32-0.82, p=0.005), and for SCD caused by non-coronary heart diseases (OR 0.34; 95% CI 0.13-0.90, p=0.030).Conclusion: IL-18 promoter -137 G/C polymorphism, which regulates the expression of IL-18, is an important predictor of SCD from any cause as well as SCD in patients with and without underlying CHD. (c) 2007 Elsevier Ireland Ltd. All rights reserved.

OBJECTIVE:Several studies support job strain as a risk factor for coronary heart disease (CHD) but null findings also exist. Individual differences in innate stress vulnerability might in part explain the mixed findings. COMT gene influences dopamine transmission and dopaminergic activity might moderate effects of stress on CHD risk. We examine whether COMT Val158Met polymorphism moderates the association between job strain and atherosclerosis.METHODS:Participants (mean age 32.5) were 347 women and 353 men from the population-based Young Finns study. Preclinical atherosclerosis was measured using carotid intima-media thickness (IMT) ultrasound.RESULTS:COMT polymorphism moderated the job strain-IMT association in men. Job strain was associated with higher IMT in Val/Val carriers but not among others.CONCLUSIONS:Our findings support a general model in which the interaction between genotype and job strain is assumed to predispose to increased atherosclerotic processes.

In the present study, we combined 2 thoroughly studied markers of inflammation and lipid metabolism—sensitive C-reactive protein (hsCRP) and apolipoprotein E genotype (apoE)—to predict mortality in the elderly (1)(2). Plasma hsCRP concentration (1) and apoE genotype(2) are both important predictors of coronary artery disease (CAD) and stroke (1)(2). The risk of myocardial infarction in people with hsCRP concentrations in the highest third of the population range is twice that of those with hsCRP in the lowest third (1). ApoE genotype is a key regulator of lipoprotein metabolisms (2)(3), and the e4-allele has been associated with increased plasma LDL cholesterol concentration and CAD (2)(3). These 2 factors are biologically linked; low hsCRP concentrations have been measured in apoE e4-allele carriers, indicating that variation in plasma hsCRP concentration is partially determined by the common apoE (e2, e3 and e4) gene polymorphism (3)(4). ApoE e4 allele …

Background Schizophrenia is a common psychiatric disease affecting about 1% of population. One major problem in the treatment is finding the right the drug for the right patients. However, pharmacogenetic results in psychiatry can seldom be replicated. Methods We selected three candidate genes associated with serotonergic neurotransmission for the study: serotonin 2A ( 5-HT2A ) receptor gene, tryptophan hydroxylase 1 ( TPH1 ) gene, and G-protein beta-3 subunit ( GNB3 ) gene. We recruited 94 schizophrenia patients representing extremes in treatment response to typical neuroleptics: 43 were good responders and 51 were poor responders. The control group consisted of 392 healthy blood donors. Results We do, in part, replicate the association between 5-HT2A T102C polymorphism and response to typical neuroleptics. In female patients, C/C genotype was significantly more common in non-responders than in responders [OR = 6.04 (95% Cl 1.67–21.93), p = 0.005] or in the control population [OR = 4.16 (95% CI 1.46–11.84), p = 0.005]. TPH1 A779C C/A genotype was inversely associated with good treatment response when compared with non-responders [OR = 0.59 (95% Cl 0.36–0.98), p = 0.030] or with the controls [OR = 0.44 (95% CI 0.23–0.86, p = 0.016], and GNB3 C825T C/T genotype showed a trend-like positive association among the male patients with a good response compared with non-responders [OR = 3.48 (95% Cl 0.92–13.25), p = 0.061], and a clearer association when compared with the controls [OR = 4.95 (95% CI 1.56–15.70), p = 0.004]. Conclusion More findings on the consequences of functional polymorphisms for the role of serotonin in the development of brain and serotonergic neurotransmission are needed before more detailed hypotheses regarding susceptibility and outcome in schizophrenia can be formulated. The present results may highlight some of the biological mechanisms in different courses of schizophrenia between men and women.

The aim of the present study was to examine an association of brain-derived neurotrophic factor (BDNF) polymorphisms G196A and C270T and the response to electroconvulsive therapy (ECT) in major depressive disorder (MDD). The study group consisted of 119 patients consecutively admitted for ECT in the Department of Psychiatry, Tampere University Hospital. All patients fulfilled the diagnostic criteria of DSM-IV for MDD. ECT was administered three times a week with a brief pulse constant current device. The Montgomery and Åsberg Depression Rating Scale (MADRS) was used as an outcome measure of depression. Genotyping was performed using fluorescent allele-specific TaqMan probes. No association between either G196A or C270T and the response to ECT was found in the whole population. There were no significant differences in responses between men and women or between psychotic and non-psychotic patients. However, within subgroups such as in psychotic and in late-onset depression CC genotype of C270T may predict good response. BDNF may not be associated with response to ECT in general, but some association in subgroups may exist.

Objective: We investigated the association between hepatic lipase (HL) C-480T polymorphism and the risk of acute myocardial infarction (AMI) as well as pre-hospital sudden cardiac death (SCD).Methods: Seven hundred sudden or unnatural pre-hospital deaths of middle-aged (33-70 years, mean 53 years) Caucasian Finnish men were subjected to detailed autopsy (Helsinki Sudden Death Study). Genotype data were obtained for 682 men.Results: In logistic regression analysis with age, body mass index, hypertension, diabetes, smoking and alcohol consumption as covariates, men with the TT genotype had an increased risk for SCD and AMI compared to CC carriers (OR = 3.0, P = 0.011; and OR = 3.7, P = 0.003). There was a significant age-by-genotype interaction (P < 0.05) on the risk of SCD. Compared to CC genotype carriers, the association between the TT genotype and SCD was particularly strong (P = 0.001) among men <53 years of age, but this association was non-significant among older men. This was mainly due to a strong association between the TT genotype and AMI due to severe coronary disease in the absence of thrombosis. Carriers of the TT genotype were more likely to have severe coronary stenoses (>= 50%) than men with the CT or CC genotype (P = 0.019).Conclusions: The results suggest that HL C-480T polymorphism, is a strong age-dependent risk factor of SCD in early middle-aged men. (C) 2006 Elsevier Ireland Ltd. All rights reserved.

Several lines of evidence suggest that catechol-O-methyltransferase (COMT) may be associated with treatment response in depression. We conducted a study on 119 patients with treatment-refractory depression admitted consecutively for electroconvulsive therapy (ECT). The COMT high/high genotype leads to a higher enzyme activity and thus lowers dopaminergic activity in the prefrontal cortex. In the present sample, those homozygous to high-active allele of COMT responded significantly more frequently to ECT.

Background/Aims: Epidermal growth factor (EGF) has widespread effects on the developing and mature nervous system. This study examined whether genetic differences in the EGF predict differences in the self-reported level of activity temperament in adults. Methods: Two hundred and ninety-two men and women from the population-based Cardiovascular Risk in Young Finns Study were genotyped for the functional EGF gene A61G polymorphisms, and their temperamental activity was assessed 3 times in 1992, 1997 and 2001. Results: The EGF gene predicted temperamental activity (the mean of 3 assessments, p = 0.007), with the G/G genotype being associated with the highest level of activity. Additional analyses in separate years indicated that the association was robust across different measurements of activity (p ≤ 0.05 in 1992 and 1997, p = 0.008 in 2001). Conclusion: These results suggest that polymorphic variation in the EGF A61 gene may be one of the factors underlying the temperament dimension of activity.

Objective Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is a major source of the superoxide anion that contributes to decreased nitric oxide bioavailability in the vasculature. The C242T polymorphism of the CYBA gene that encodes p22phox, a component of NADPH oxidase, has been found to modulate superoxide production. We examined the relationship of the C242T polymorphism with endothelial-dependent brachial artery flow-mediated vasodilatation (FMD) in a population-based sample of young healthy adults. Methods FMD, defined as the increased percentage in brachial artery diameter after reactive hyperemia, was assessed by ultrasound and the C242T polymorphism using a 5′ nuclease assay in 2058 subjects aged 24–39 years. Results The mean values of brachial artery FMD were 8.0 ± 4.4% in all study subjects (n = 2058), and 7.8 ± 4.4, 8.2 ± 4.5, and 8.7 ± 4.5% in subjects with the CC (n = 1362), CT (n = 616), and TT (n = 80) genotypes of the C242T CYBA polymorphism, respectively (P = 0.02 for trend). The association remained significant (P = 0.019) in multivariate analyses adjusted for age, sex, obesity indices, smoking habits, blood pressure, serum glucose, lipids, and C-reactive protein. The relationship between FMD and the C242T polymorphism was stronger (P = 0.004) in overweight subjects (body mass index ≥ 25 kg/m2, n = 895) and ever-smokers (P = 0.008, n = 1082), whereas no relationship was found in normal-weight subjects and non-smokers (P = 0.824 and P = 0.438, respectively). Conclusion The C242T polymorphism of the CYBA gene seems to be related to endothelial function in a population-based sample of young healthy adults. Overweight and smoking status may modify this genetic effect.

BACKGROUNDThe present study was designed to investigate the effects of apoB XbaI and apoA-I/C-III/A-IV SstI polymorphisms to carotid artery intima-media thickness (IMT), carotid artery compliance (CAC) and brachial artery flow-mediated vasodilatation (FMD).METHODS AND RESULTSAs part of the Cardiovascular Risk in Young Finns Study, the carotid IMT, CAC and brachial FMD of 2,265 subjects (mean age +/- SD 32 +/-5 years) were measured with ultrasonography, and genotyping of the apolipoprotein polymorphisms was performed. The frequencies of the genotypes did not differ between the groups with high (above median 0.57 mm) and low (below median) IMT, CAC or FMD. The average carotid IMT differed between the 3 apoB XbaI genotypes (ANOVA, p=0.04), but not between the apoA-I/C-III/A-IV SstI genotypes (ANOVA, p=0.53). The relationship between the polymorphisms and carotid IMT was not significant in any of the covariate-adjusted logistic and linear regression analyses. CAC and FMD were not influenced by either of the polymorphisms in ANOVA and regression analyses.CONCLUSIONSThe polymorphisms apoA-I/C-III/A-IV SstI and apoB XbaI do not seem to affect carotid artery characteristics or brachial artery FMD in young adulthood.