Lovisa A. Olsson

The International Physical Activity Questionnaire modified for the elderly: aspects of validity and feasibility.

OBJECTIVE To modify the self-administered, short version of the International Physical Activity Questionnaire (IPAQ) for adults to be used in the elderly (aged 65 years and above), and to validate this modified IPAQ for the elderly (IPAQ-E). DESIGN A direct validity study using accelerometer-measured physical activity (PA) as the criterion measure, and an indirect criterion validity study using high-sensitivity C-reactive protein (hs-CRP) as a biological marker of activity. SETTING Organisations for retired persons in Sweden. SUBJECTS The direct validity study consisted of fifty-four participants and the indirect criterion validity study consisted of 359 participants. All participants were retired persons (66-91 years) living independently. RESULTS All self-reported activity domains (sitting, walking, moderate and vigorous) were positively correlated with the corresponding variable objectively assessed by an accelerometer (ρ = 0·277-0·471), but a systematic error was observed. The specificity of IPAQ-E to identify low-active participants was 85 %, and the sensitivity to identify the more active participants was 81 %. A main effect of IPAQ-E category (Low, Moderate or High) was observed for hs-CRP (P = 0·041). CONCLUSIONS We found this modified version of IPAQ, the IPAQ-E, to be well accepted by our sample of socially active elderly. It provided acceptable estimates of PA, well in line with other questionnaires, even though it had a systematic error. The IPAQ-E was able to identify an expected response of a biomarker (hs-CRP) to PA. We recommend the use of the IPAQ-E to classify participants aged 65 years and above into PA categories, to rank individuals or to identify individuals meeting certain PA criteria.

Simultaneous genotyping of the three lactose tolerance-linked polymorphisms LCT -13907C>G, LCT -13910C>T and LCT -13915T>G with Pyrosequencing technology.

Abstract Background: We required a new genotyping method for the diagnosis of adult hypolactasia, which would allow the simultaneous genotyping of three known polymorphic loci linked to lactose tolerance (LCT –13907C>G, LCT –13910C>T and LCT –13915T>G) in a single PCR/pyrosequencing test run. Method: We utilized Pyrosequencing™ technology, a DNA-sequence-by-synthesis technique. Results: The developed Pyrosequencing™ method allowed genotyping of the three loci LCT –13907C>G, LCT –13910C>T and LCT –13915T>G in a single PCR/pyrosequencing test run. A separate Pyrosequencing™ assay was developed for genotyping of the LCT –14010G>C mutation. The methods were evaluated in 116 clinical samples from patients of non-European descent, sent to the laboratory for diagnosis of adult hypolactasia. The “African” mutations LCT –13907C>G and LCT –13915T>G were found in subjects originating not only from Somalia, Ethiopia and Eritrea but also in Arabs and Iranians. Several compound heterozygotes LCT –13907CG/–13915TG were found among Ethiopian, Eritrean and Somalian subjects. No subject with the LCT –14010G>C mutation was found among the studied subjects. Advantages compared to the other genotyping methods are less staff hands-on time than, e.g., restriction fragment length polymorphism (RFLP) analyses, avoiding radioactivity as in the originally described isotope-minisequencing and in addition, Pyrosequencing™ is a direct DNA sequencing technique which gives unambiguous genotyping results as well as some redundant sequence information beyond the single nucleotide polymorphism (SNP) position, which serves as a valuable internal control obtained for each sample. Conclusions: Pyrosequencing™ is a robust genotyping modality suitable for clinical genotyping of patients not only of European, but also of African or Middle Eastern descent, who may harbor any combination of the three LCT mutations, LCT –13907C>G, LCT –13910C>T, LCT –13915T>G. Clin Chem Lab Med 2008;46:80–4.

Subjective well-being in Swedish active seniors or seniors with cognitive complaints and its relation to commonly available biomarkers

Well-being (WB) is a complex variable in its relation to physical health and other personal and social characteristics. The aim was to study subjective well-being (SWB) and its possible associations with traditional biomarkers of cardiovascular risk or dementia, in Swedish seniors. SWB was estimated by the Psychological General Well-Being (PGWB) index in two study groups. The active seniors (AS) group consisted of community-dwelling elderly Swedes leading an active life (n=389). The DGM cohort (n=300) consisted of subjects referred to the Memory Unit at the Department of Geriatrics, the cognitive problems had to be subjective, mild or moderate (MMSE≥10). There were differences in all six subdimensions of SWB or distress, and in the sum of PGWB scores, between the two study groups (p<0.001 for all), and adjustment for differences in biomarkers of somatic health (age, sex, blood pressure, BMI, HDL cholesterol, ApoB/ApoA1 ratio, creatinine, and homocysteine) did not attenuate these differences. In addition, cognition as assessed by the Clock-Drawing Test (CDT) showed independent associations with four of the PGWB subdimensions and with the PGWB sum. Among the subjects in the DGM cohort, SWB was equally low among subjects with an MCI (minor cognitive impairment) diagnosis or without a dementia diagnosis as among subjects diagnosed with dementia disorder. We conclude that the nosological grouping variable (AS vs. DGM cohort) and a cognitive factor were the main independent predictors of SWB in this sample of elderly Swedes, whereas biomarkers of somatic health played a subordinated role.

Association of common variants of UCP2 gene with low-grade inflammation in Swedish children and adolescents; the European Youth Heart Study.

We examined the associations of two functional variants 866G>A and DEL/INS polymorphisms of UCP2 gene with low-grade inflammatory proteins (C-reactive protein, fibrinogen, complement C3 [C3], and complement C4 [C4]) in 131 children (52.7% boys, aged 9.5 ± 0.4 y) and 118 adolescents (44.1% males, aged 15.5 ± 0.4 y) selected from the European Youth Heart Study. Differences in inflammatory markers among the genotype variants of the two UCP2 gene polymorphisms were analyzed after adjusting for sex, age, pubertal stage, fitness, and fatness. The results showed that fibrinogen, C3, and C4 were higher in GG carriers than in subjects carrying the A allele of the 866G>A polymorphism of the UCP2 gene (UCP2 −866G>A) polymorphism (all p < 0.05). The DEL/DEL genotype of 45nt deletion/insertion variant polymorphism of the UCP2 gene (UCP2 DEL/INS) was associated with higher C3 (p < 0.05) than DEL/INS and INS/INS genotypes. This study provides evidence of a role of UCP2 −866G>A in modifying low-grade inflammatory state in apparently healthy children and adolescents. Given the implication of complement factors on atherosclerosis process, these results contribute to explain the reduced cardiovascular risk associated with the A allele of the UCP2 −866G>A polymorphism.

Lactase persistence versus lactose intolerance: Is there an intermediate phenotype?

BACKGROUND According to the prevailing theory about the genetic background to lactose intolerance, there are three genotypes but only two adult physiological phenotypes: lactase persistence in individuals with the CT and TT genotypes and lactase non-persistence in individuals with the CC genotype. However, analysis of lactase activity from intestinal biopsies has revealed three distinct levels of activity, suggesting that an intermediate physiological phenotype may exist. AIM To assess possible disparities between different genotypes with regard to biomarkers of lactase activity and physical symptoms during an oral lactose load test. METHODS A retrospective study using an oral lactose load test (n=487). Concentrations of hydrogen in exhaled air and blood glucose were measured. Afterwards, subjects were asked to provide oral mucosa samples for genotyping and answer a questionnaire (participation rate 56%, n=274). RESULTS Mean hydrogen levels in exhaled air at 120min were significantly higher in the CT genotype than in the TT genotype. There was no significant difference in blood glucose levels between the two groups. Reported symptoms, with the possible exception of abdominal pain, were equally prevalent in both groups. CONCLUSIONS Subjects with the CT and TT genotypes, hitherto classified as lactase-persistent, differ in their physiological response to lactose intake, indicating differences in phenotype which could have clinical significance.

Subjective well-being in Swedish active seniors and its relationship with physical activity and commonly available biomarkers

Background Physical activity is claimed to be related to well-being and to a lower risk of cardiovascular disease. Therefore, the possible associations of well-being with physical activity and biomarkers of somatic health were studied in a sample of Swedish active seniors to determine the strength of these associations. Methods Three hundred and eighty-nine community-dwelling senior citizens (127 men and 262 women) of mean age 74±5 years were recruited for this cross-sectional population study. Serum samples were analyzed for lipoproteins and markers of inflammation. The Psychological General Well-Being (PGWB) index was used to measure subjective well-being. Physical activity was assessed by the International Physical Activity Questionnaire modified for the elderly. Results More than 50% of men and women rated their physical activity as high; in the women, there was a significant difference between the age groups (younger and older than the median age [median =74.1 years], respectively). The mean PGWB index indicates a high degree of subjective well-being in this group of Swedish seniors. Of the PGWB subdimensions, general health had the strongest positive relationship with physical activity (r2=5.4%). For the subdimensions of depressed mood, positive well-being, vitality, and PGWB index, physical activity had an r2 ≤4%, while the contributions of sex, age, and biomarkers were minor. Conclusion We have estimated the contribution of physical activity to the variance of subjective well-being in active seniors. Physical activity appears to play a greater role as a determinant of subjective well-being than do biomarkers of somatic health, especially in females, but most of the variance remained unaccounted for by the studied variables.

Measured glomerular filtration rate does not improve prediction of mortality by cystatin C and creatinine

Background Cystatin C may add explanatory power for associations with mortality in combination with other filtration markers, possibly indicating pathways other than glomerular filtration rate (GFR). However, this has not been firmly established since interpretation of associations independent of measured GFR (mGFR) is limited by potential multicollinearity between markers of GFR. The primary aim of this study was to assess associations between cystatin C and mortality, independent of mGFR. A secondary aim was to evaluate the utility of combining cystatin C and creatinine to predict mortality risk. Methods Cox regression was used to assess the associations of cystatin C and creatinine with mortality in 1157 individuals referred for assessment of plasma clearance of iohexol. Results Since cystatin C and creatinine are inversely related to mGFR, cystatin C - 1 and creatinine - 1 were used. After adjustment for mGFR, lower cystatin C - 1 (higher cystatin C concentration) and higher creatinine - 1 (lower creatinine concentration) were independently associated with increased mortality. When nested models were compared, avoiding the potential influence of multicollinearity, the independence of the associations was supported. Among models combining the markers of GFR, adjusted for demographic factors and comorbidity, cystatin C - 1 and creatinine - 1 combined explained the largest proportion of variance in associations with mortality risk ( R 2  = 0.61). Addition of mGFR did not improve the model. Conclusions Our results suggest that both creatinine and cystatin C have independent associations with mortality not explained entirely by mGFR and that mGFR does not offer a more precise mortality risk assessment than these endogenous filtration markers combined.

Cardiorespiratory fitness modifies the association between the UCP3-55C>T (rs1800849) polymorphism and plasma homocysteine in Swedish youth.

OBJECTIVE Whether the polymorphisms in the UCP3 gene have an influence on plasma homocysteine levels during youth is not known, and to elucidate the putative modifying role of fitness is also of clinical interest. We analysed the association between polymorphisms in the UCP3 gene and plasma homocysteine in youth and to examine whether fitness modifies this association. METHODS The study population comprised 267 Swedish children (8-10 years) and 305 adolescents (14-16 years). Fasting total plasma homocysteine was the outcome variable. We genotyped five UCP3 polymorphisms (rs1800849, rs1800006, rs2075577, rs647126, and rs591758) and one MTHFR 677C>T (rs1801133) polymorphism. Cardiorespiratory fitness was measured with a maximal ergometer bike test. RESULTS Youth homozygous or heterozygous for the T allele of the rs1800849 polymorphism had significantly higher levels of homocysteine than those carrying the CC genotype (8.56+/-4.72 micromol/L vs. 7.72+/-2.73 micromol/L, respectively, P=0.011) after adjusting for gender, age, pubertal status, folate and vitamin B(12) intake and MTHFR 677C>T polymorphism, whereas no association was observed for the other analysed polymorphisms. There was a significant interaction effect of fitnessxrs1800849 polymorphism (P=0.042). The effect of the rs1800849 polymorphism on homocysteine levels persisted in youth with low fitness, whereas it was abolished in those with moderate or high cardiorespiratory fitness (P>0.1). CONCLUSIONS Cardiorespiratory fitness modifies the association between the rs1800849 polymorphism and homocysteine so that the negative effect of the T allele does not persist in youth with moderate to high levels of fitness.

Identification of novel genetic variants in the mutational hotspot region 14 kb upstream of the LCT gene in a Mexican population

Abstract Several polymorphic loci linked to lactase persistence (LP) have been described, all located in a small mutational hotspot region far upstream (∼14 kb) of the lactase (LCT) gene. One is typically found in Europeans, LCT –13910C > T, several others are found in East Africans and Arabs, e.g. LCT –13907C > G and LCT –13915T > G. The possibility of similar loci, specific to populations in South and Central America, has not received much attention so far. To identify possible novel polymorphisms in the mutational hotspot region, we sampled 158 subjects from a rural area in South-Central Mexico. DNA was isolated from serum, and Sanger sequencing of a 501 bp region spanning the LCT –13910C > T hotspot was successfully performed in 150 samples. The frequency of the European-type LCT –13910 T-allele was q = 0.202, and 35% of the population was thus lactase-persistent (CT or TT). Sixteen novel genetic variants were found amongst 11 of the subjects, all were heterozygotes: seven of the subjects were also carriers of at least one LCT –13910 T-allele. Thus, the mutational hotspot region is also a hotspot in the rural Mexican population: 11/150 subjects carried a total of 16 previously unknown private mutations but no novel polymorphism was found. The relationship between such novel genetic variants in Mexicans and lactase persistence is worthy of more investigation.

Self-reported sitting time, physical activity and fibrinolytic and other novel cardio-metabolic biomarkers in active Swedish seniors

Background Too much sitting is linked with an increased risk of cardiovascular disease and mortality. The mediating mechanisms for these associations are largely unknown, however dysregulated fibrinolysis have emerged as a possible contributor. Objective We examined the associations of self-reported overall sitting time and physical activity with fibrinolytic and other novel cardio-metabolic biomarkers in older adults. Materials and Methods Data was analysed for 364 participants (74±7 yrs) of the Active Seniors group (retired, living independently in their own homes). Linear regression analyses examined associations of categories of categories of sitting time (≤3, 3–6, >6 hrs/day) and overall physical activity (Low, Moderate and High) with biomarkers in serum or plasma, adjusting for age, gender and smoking (with further adjustment for either overall physical activity or sitting time and BMI in secondary analyses). Results Compared to sitting ≤ 3 hrs/day, sitting >6 hrs/day was associated with higher tissue plasminogen activator (tPA) and tissue plasminogen activator/plasminogen activator inhibitor-1 complex (tPA-PAI-1 complex). These associations were not independent of overall physical activity or BMI. Compared to those in the high physical activity, low physical activity was associated with a higher BMI, high-sensitivity C-reactive protein (hs-CRP) and tPA-PAI-1 complex levels. Only the associations of BMI and hs-CRP were independent of sitting time. Conclusions These findings provide preliminary cross-sectional evidence for the relationships of sitting time with fibrinolytic markers in older adults. They also reinforce the importance of regular physical activity for cardio-metabolic health.