The prevalence of hemoglobin Tacoma in Finland detected by HbA1c capillary electrophoresis.

Previous studies have identified occasional cases of heterozygous Hb Tacoma in areas that have attracted Finnish immigrants, especially in Sweden and North America, but large studies of this slightly unstable beta variant in vitro have not been carried out. Here we determined the prevalence of hemoglobin variants across Finland. A total of 5059 samples from 11 different hospital districts were analyzed using HbA1c capillary electrophoresis and reviewed for atypical profiles (HbA1c, Capillarys 3 Tera, Sebia). 38 heterozygous Hb Tacoma cases were found (0.75%). The prevalence was highest in South Ostrobothnia (2.0%), located in western Finland, and second highest in the neighboring provinces (1.0-1.4%), but only two districts were devoid of variants. Heterozygous Hb Tacoma was confirmed by genetic testing (NM_000518.5(HBB):c.93G > T (p.Arg31Ser)). In addition, five other variants were found, suggestive of HbE, Hb Helsinki (two cases) and an alpha variant, as interpreted from the electropherograms. The fifth variant, belonging to the South Ostrobothnian cohort, remained unknown at the time of the initial analyses, but was later interpreted as homozygous Hb Tacoma and confirmed by hemoglobin fraction analysis (Hemoglobin(E), Capillarys 3 Tera). In a subsequent retrospective study of the electropherograms of routine HbA1c diagnostics, altogether nine homozygous Hb Tacoma cases were identified in South Ostrobothnia. While heterozygous Hb Tacoma is usually an incidental finding, it interferes with several HbA1c assays. The present study is the first demonstration of homozygous Hb Tacoma. The clinical presentations of homozygous Hb Tacoma are not known and need to be addressed in future studies.

APOE Genotypes, Lipid Profiles, and Associated Clinical Markers in a Finnish Population with Cardiovascular Disease Risk Factors.

INTRODUCTION: The APOE ε4 allele predisposes to high cholesterol and increases the risk for lifestyle-related diseases such as Alzheimer's disease and cardiovascular diseases (CVDs). The aim of this study was to analyse interrelationships of APOE genotypes with lipid metabolism and lifestyle factors in middle-aged Finns among whom the CVD risk factors are common. METHODS: Participants (n = 211) were analysed for APOE ε genotypes, physiological parameters, and health- and diet-related plasma markers. Lifestyle choices were determined by a questionnaire. RESULTS: APOE genotypes ε3/ε4 and ε4/ε4 (ε4 group) represented 34.1% of the participants. Genotype ε3/ε3 (ε3 group) frequency was 54.5%. Carriers of ε2 (ε2 group; ε2/ε2, ε2/ε3 and ε2/ε4) represented 11.4%; 1.9% were of the genotype ε2/ε4. LDL and total cholesterol levels were lower (p < 0.05) in the ε2 carriers than in the ε3 or ε4 groups, while the ε3 and ε4 groups did not differ. Proportions of plasma saturated fatty acids (SFAs) were higher (p < 0.01), and omega-6 fatty acids lower (p = 0.01) in the ε2 carriers compared with the ε4 group. The ε2 carriers had a higher (p < 0.05) percentage of 22:4n-6 and 22:5n-6 and a lower (p < 0.05) percentage of 24:5n-3 and 24:6n-3 than individuals without the ε2 allele. CONCLUSIONS: The plasma fatty-acid profiles in the ε2 group were characterized by higher SFA and lower omega-6 fatty-acid proportions. Their lower cholesterol values indicated a lower risk for CVD compared with the ε4 group. A novel finding was that the ε2 carriers had different proportions of 22:4n-6, 22:5n-6, 24:5n-3, and 24:6n-3 than individuals without the ε2 allele. The significance of the differences in fatty-acid composition remains to be studied.

APOE Genotype Disclosure and Lifestyle Advice in a Randomized Intervention Study with Finnish Participants.

BACKGROUND: The APOE ε4 allele is associated with higher risks of cardiovascular diseases and Alzheimer disease than ε3 and ε2. OBJECTIVES: We studied the effectiveness of dietary and lifestyle guidance and personal genetic risk information [ε4 carrier (ε4+); ε4 noncarrier (ε4-)] as motivators for a healthier lifestyle. METHODS: A total of 188 healthy Finnish volunteers (82.4% women; mean ± SD age: 51.0 ± 5.6 y; BMI: 26.0 ± 3.6 kg/m2; total cholesterol: 5.2 ± 0.9 mmol/L) participated in our randomized intervention study. The participants were genotyped for APOE and divided into intervention (INT; INTε4+, n = 33; INTε4-, n = 57) and control groups (CTRL; CTRLε4+, n = 36; CTRLε4-, n = 62). Blood samples, measured observations, and questionnaire data were obtained at baseline and at 1 and 1.5 y. INT participants received their ε4 carrier status at baseline. Monthly Internet-based guidance based on the Finnish Dietary guidelines was provided for all. RESULTS: The proportion of SFAs in plasma over time fluctuated less in INTε4+ than in the other groups (P-interaction < 0.05; primary outcome). The lifestyle guidance increased vegetable consumption from 3.5 to 3.6 portions/d, improved the dietary fat quality score by 5.3%, increased the plasma n-3 (ω-3) FA proportion by 7.3%, and decreased the consumption of high-fat/high-sugar foods from 7.3 to 6.5 portions/wk and total- and LDL-cholesterol concentrations by 4.3% and 6.1%, respectively, in the entire participant population (P < 0.05; secondary outcome). Compared with the ε4- participants, ε4+ participants had 2.4% higher plasma n-6 (ω-6) FA, lower C-peptide (3.9 compared with 4.2 nmol/L × h) and sensitive C-reactive protein values, and decreased plasma malondialdehyde concentrations over time (P < 0.05; secondary outcome). CONCLUSIONS: Lifestyle guidance given to healthy Finnish participants yielded small but beneficial changes. The INTε4+ group did not seem markedly more responsive to the guidance than the other groups.This trial was registered at clinicaltrials.gov as NCT03794141.

A Long-Term Follow-Up Study on Disclosing Genetic Risk Information (APOE) to Promote Healthy Lifestyles in Finland.

AIM: This observational follow-up study was designed to assess the long-term behavioural and clinical effects of receiving personal genetic risk information. The information disclosed was the carrier status of the apolipoprotein E (APOE)alleles, which differentially contribute to the genetic risk for cardiovascular disease (CVD) and Alzheimer's disease. METHODS: This study forms a continuum with a previous 1-year intervention (2010-2011) monitoring the effects of disclosing the carrier status of the APOE ε4risk allele. The follow-up measurements, performed 5.5 years post-intervention, included clinical measurements (blood values and anthropomorphic parameters) and questionnaires (psychological and behavioural factors). The participants were healthy adult volunteers, aged 26-73 years (n = 70) who had participated in the previous intervention, and received their APOE allele status either at the beginning (former test group) or the end of the intervention (former control group). RESULTS: Personal genetic risk information resulted in a moderate health-conscious change in diet and had a slight positive long-term effect on clinical factors, particularly the serum lipids. These improvements were subsequent to the disclosure of genetic information and occurred mainly in the APOE ε4-positive members of the former control group, that is, those who were at increased genetic risk for CVD but had not been informed of their status before the end of the intervention. In contrast, changes in the values and health behaviour of the APOE ε4-positive individuals in the former test group, who had already changed their health behaviour during the previous intervention as a result of being informed of their carrier status, varied more: some continued to improve, some remained at their previously improved level, and some relapsed slightly. Both groups had nonetheless displayed an improvement immediately subsequent to the disclosure of their personal genetic risk. CONCLUSION: Receiving information on increased personal genetic risk (carrier status of APOE ε4)for CVD provided the motivation for improvements in health behaviour. The resulting changes, while modest, in most cases remained visible even after a number of years.

Serum soluble urokinase plasminogen activator receptor in alcoholics: relation to liver disease severity, fibrogenesis, and alcohol use.

BACKGROUND AND AIM: Heavy alcohol consumption may lead to development of liver disease and the need for non-invasive parameters for detecting those at risk is widely acknowledged. METHODS: We measured serum soluble urokinase-type plasminogen activator receptor (suPAR) levels from 63 patients with alcoholic liver disease (ALD), 57 heavy drinkers without apparent liver disease, and 39 controls who were either moderate drinkers or abstainers. RESULTS: The highest serum suPAR concentrations were detected in patients with ALD (P < 0.001) showing high diagnostic accuracy in differentiating ALD patients from heavy drinkers without liver disease (area under curve 0.921, P < 0.001). Levels of suPAR correlated positively with serum markers of fibrogenesis (aminoterminal propeptide of type III procollagen and hyaluronic acid) (P < 0.001), with clinical (combined clinical and laboratory index P < 0.01) and morphological (combined morphological index P < 0.05) indices of liver disease severity and with the stage of fibrosis (P < 0.01). The suPAR concentrations were also elevated in heavy drinkers when compared with healthy controls (P < 0.001). CONCLUSION: The data indicate that serum suPAR concentrations are increased as a result of heavy alcohol consumption and further with development of ALD, showing a good diagnostic performance in detecting those with liver disease. The association with the histological severity of ALD and correlation with fibrosis indicates potential of serum suPAR also as a prognostic marker in ALD.

Isolation of drugs from biological fluids by using pH sensitive poly(acrylic acid) grafted poly(vinylidene fluoride) polymer membrane in vitro.

Isolation of acidic and basic model drugs by using pH sensitive poly(acrylic acid) grafted poly(vinylidene fluoride) (PAA-PVDF) cation-exchange membrane from biological fluids was reported. Effects of drug charge and lipophilicity on adsorption were also investigated. In the present study, basic model drugs adsorbed to a considerably greater extent onto the membrane than acidic drugs. Albumin was not adsorbed onto the membrane. Results of our study exposed, that electrostatic interactions between positively charged basic drug and negatively charged PVDF-PAA membrane were the most important factor affecting drug adsorption onto the membrane. Adsorption of acidic and basic drugs onto the PVDF-PAA membrane was not related to drug lipophilicity. The results of present study demonstrated that basic drugs adsorbed extensively onto the membrane, but albumin did not, proposing that PAA-PVDF membrane may be suitable for isolating basic drugs from proteinaceous biological fluids (i.e. serum) for subsequent monitoring and evaluation.

Adsorption of drugs onto a pH responsive poly(N,N-dimethyl aminoethyl methacrylate) grafted anion-exchange membrane in vitro.

The influence of charge and lipophilicity of acidic and basic model drugs on their adsorption onto poly(N,N-dimethyl aminoethyl methacrylic acid) grafted poly(vinylidene fluoride) (DMAEMA-PVDF) membranes was evaluated. The effect of serum proteins (albumin, IgG) and hormones (cortisol, free thyroxine (T(4)F) and thyrotropin (TSH)) on drug adsorption was also studied. Acidic model drugs (antiepileptics and benzodiazepies) adsorbed to a greater extent onto the membrane from Hepes buffer at ionic strength of 25mM and pH 7.0 than basic drugs (antidepressants) did. Adsorption of acidic model drugs was based on electrostatic interactions between positively charged tertiary amino groups of DMAEMA side-chain and acidic negatively charged drug. Albumin diminished the adsorption of drugs from serum onto the membrane. Lipophilicity was related to the adsorption of acidic model drugs from serum onto the membrane. The degree of grafting had the greatest effect on adsorption of lipophilic drugs, but no influence was observed on adsorption of hydrophilic drugs. The present results showed that acidic drugs and albumin adsorbed onto the membrane, which suggests that the PVDF-DMAEMA membrane may be suitable for separating acidic drugs from protein-free substances for subsequent monitoring and evaluation.