Biomedical subjects

U de Faire

Publications and source records attributed to U de Faire.

At least 19 recordsLinked to original sources

PubMed2006

High intake of alcohol is associated with newly diagnosed diabetes in 60 years old men and women.

BACKGROUND AND AIMS: Low or moderate alcohol intake has been found to be protective against the incidence of diabetes, while conflicting results have been found regarding high alcohol intake. This study aimed at evaluating the effect of alcohol intake on newly diagnosed diabetes among subjects aged 60 years in relation to anthropometric measurements, life-style and socio-economic factors. METHODS AND RESULTS: A population-based cross-sectional study of 4106 individuals, 1973 men and 2133 women, aged 60 years, in Stockholm County, Sweden. Medical history, socio-economic factors and life-style data were collected by a questionnaire and a medical examination including laboratory tests. High total intake of alcohol, i.e. >30 g/day vs. 0-30 g/day, was significantly noted more often in newly diagnosed diabetes in men (OR 2.72, 95% CI 1.70-4.34), even when adjusting for other factors, i.e. anthropometric measurements, life-style, socio-economic and dietary factors (adjusted OR 1.94, 95% CI 1.17-3.23); a high intake of spirits, i.e. >15 g/day vs. 0-15 g/day, was significantly more often observed among women (OR 3.97, 95% CI 1.50-10.50), however, it was not significant after adjustment (OR 2.23, 95% CI 0.67-7.42). CONCLUSION: High intake of alcohol among men was associated with increased risk of diabetes even when adjusting for other factors.

Alcohol Drinking↗

PubMed2006

Fatty acid handling protein expression in adipose tissue, fatty acid composition of adipose tissue and serum, and markers of insulin resistance.

OBJECTIVE: Proteins involved in cellular fatty acid (FA) uptake and metabolism may be of relevance in the context of disturbed FA metabolism associated with insulin resistance. Therefore this study investigated relationships between FA handling protein mRNA expression in adipose tissue, FA composition of adipose tissue and serum, and markers of insulin resistance. SUBJECTS: 75 subjects with a range of insulin sensitivities recruited from a cohort of 294 healthy 63-year-old Swedish men. MEASUREMENTS: Anthropometric and biochemical variables (e.g. waist-hip-ratio (WHR) and homeostasis model assessment (HOMA) index of insulin sensitivity), FA composition of the subcutaneous (s.c.) gluteal adipose tissue, serum nonesterified FA (NEFA) and serum phospholipid compartments (by gas-liquid chromatography; n = 294), and mRNA levels of FA handling proteins (adipocyte and keratinocyte lipid binding proteins, fatty acid transport protein (FATP) -1 and -4, CD36/fatty acid translocase, plasma membrane fatty acid binding protein, and acyl-CoA synthase-1 (ACS1)) in s.c. gluteal adipose tissue (by quantitative real-time polymerase chain reaction; n = 75). RESULTS: ACS1 expression was negatively correlated with measures of insulin resistance and central obesity (ACS1 versus HOMA: r = -0.28, P<0.05; ACS1 versus WHR: r = -0.23, P<0.05), with an opposite trend for FATP4. Further analysis of ACS1 expression levels revealed correlations with adipose tissue 16:0 (r = -0.27, P<0.05) and NEFA 16:1 (r = 0.29, P<0.05), FA composition variables which in turn correlated with HOMA index (r = 0.39, P<0.001 and r = -0.23, P<0.05, respectively, n = 75). Moreover, NEFA 16:1 predicted ACS1 expression independently of HOMA, WHR and adipose tissue 16:0 in multiple regression analysis (standardized coefficient = 0.27, P<0.05). CONCLUSION: Significant associations were found between measures of insulin sensitivity, adipose tissue FA handling protein expression, and specific FA composition variables. Although causal relationships could not be identified these findings suggest a role of FA handling proteins in relation to insulin sensitivity, via their involvement in FA trafficking and metabolism. In particular they indicate links between ACS1 activity, the distribution of 16:0 and 16:1, and insulin sensitivity, which may be of physiological relevance.

Adipose Tissue↗

PubMed2005

Association of TNF-alpha serum levels and TNFA promoter polymorphisms with risk of myocardial infarction.

Elevated levels of tumor necrosis factor-alpha (TNF-alpha), and presence of polymorphisms of the TNFA gene have been implicated in cardiovascular disease pathogenesis. We explored the relationship between polymorphisms in the TNFA gene (-1031C/T, -863C/A -857T/C, -308G/A, -238G/A), protein levels of TNF-alpha and their association to myocardial infarction (MI) using a sample of 1213 post-MI patients and 1561 healthy controls. MI risk was higher among men with elevated TNF-alpha levels, with the highest compared to the lowest TNF-alpha quartile giving a 70% risk increase (OR [95% CI]: 1.7 [1.1; 2.6]). Obese subjects who also had elevated TNF-alpha levels were at even higher risk for MI (OR [95% CI]: 3.4 [2.1; 5.6]). Higher TNF-alpha levels were seen among smokers (but not among non-smokers) carrying the -857T allele. Furthermore, a rare haplotype occurred more frequently among the cases than the controls. Elevated TNF-alpha levels are associated with increased MI risk. Obese subjects with elevated TNF-a levels, and carriers of polymorphisms in or near TNFA are particularly susceptible to the hazards of smoking, results which may have implications for cardiovascular preventive measures.

Aged↗

PubMed2005

The relation between alcohol intake and physical activity and the fatty acids 14 : 0, 15 : 0 and 17 : 0 in serum phospholipids and adipose tissue used as markers for dairy fat intake.

The relative contents of the fatty acids 14 : 0, 15 : 0 and 17 : 0 in serum and adipose tissue may be used as biological markers of dairy fat intake. However, the determinants of these fatty acids are not fully understood. This study investigates the relationship between these fatty acids and the intake of macronutrients and physical activity in a cross-sectional study of 301 healthy men aged 61-64 years. Dietary intake was assessed using a pre-coded 7 d food record, and physical activity during the previous year was recorded in an interview. Under-reporters of energy intake were identified by the Goldberg cut-off. Fatty acid composition was determined in serum phospholipids (PL) and subcutaneous adipose tissue (AT) from the upper buttock. The relative content of each of 14 : 0, 15 : 0 and 17 : 0 in PL and AT was positively associated with the intake of dairy fat. In addition, all three fatty acids were inversely correlated with alcohol intake, R ranging from -0.28 to -0.53 (P<0.001). The results were not markedly affected when under-reporters (n 88) were excluded from the analyses. In both PL and AT, the relative content of the fatty acids was approximately 5% higher in a group of high physical activity compared with a group of low physical activity, although significant trends were only seen for 14 : 0 in PL and 17 : 0 in AT. The findings suggest that adjustments should be made for alcohol intake when the fatty acids 14 : 0, 15 : 0 and 17 : 0 are applied as markers for dairy fat intake.

Adipose Tissue↗

PubMed2005

Increased risk of heart failure as a consequence of perioperative myocardial injury after coronary artery bypass grafting.

OBJECTIVE: To analyse the relation between perioperative myocardial injury (PMI) and the risk of subsequent heart failure after coronary artery bypass grafting (CABG). DESIGN AND SETTING: Clinical data were documented prospectively in all patients and stored in a computer. All hospital readmissions were identified and the registered primary diagnoses were analysed. Survival information on all patients was obtained by use of combined registers. The study was carried out at the cardiac surgical referral centre of University Hospital, Uppsala, Sweden. PATIENTS: 7493 patients discharged alive after primary CABG between 1987 and 1996 were followed up until the first hospital readmission for heart failure, death, or 31 December 1996 was reached. MAIN OUTCOME MEASURES: Hospital readmission for heart failure or late mortality. RESULTS: Of the patients studied 576 (7.7%) were readmitted for heart failure. Actuarial freedom from readmission for heart failure after four years was 93%, and after seven years, 89%. Of the 576 patients, 114 (20%) had had PMI, which increased the risk of heart failure independently (hazard ratio (HR) 2.3, 95% confidence interval (CI) 1.8 to 2.8). Increased age, female sex, diabetes, previous myocardial infarction, dyspnoea, preoperative atrial fibrillation, left ventricular dysfunction, and triple vessel disease were independent risk factors for heart failure. The use of an internal mammary artery decreased the risk. PMI implied increased mortality (HR 1.4, 95% CI 1.1 to 1.8). Late mortality was greatly increased in patients readmitted for heart failure. CONCLUSION: PMI increased the risk of heart failure and late death after CABG, and heart failure had a notable adverse effect on late survival.

Adult↗

PubMed2004

Associations between the intake of dairy fat and calcium and abdominal obesity.

OBJECTIVE: This study evaluates the association between abdominal obesity and the intake of dairy fat and calcium using information from dietary data and the relative content of the fatty acids 14:0, 15:0, and 17 : 0 in serum phospholipids (PL) and adipose tissue (AT), which are suggested biological markers for dairy fat intake. This study also explores how the associations were affected when under-reporters (URs) were separated from the analyses. DESIGN: Cross-sectional study. SUBJECTS: In all, 301 healthy 63-y-old men with different degrees of fasting-insulin concentrations. METHODS: Sagittal abdominal obesity (SAD), dietary intake assessed by a 7-day food registration, and the fatty acid composition in serum PL and AT were measured. URs (n=88) and non-under-reporters (non-URs, n=213) were identified by Goldberg's equation, which compares energy intake with energy expenditure, both expressed as multiples of the basal metabolic rate. RESULTS: The intake of dairy fat, expressed as g/100 g fat, was inversely correlated with SAD; however, this association was only observed in the URs (r=-0.36, P=0.001) and not in the non-URs (r=-0.04, P=0.59). The intake of calcium was inversely correlated with SAD in both groups, although the association was weaker in the non-URs. The intake of dairy fat was related to the relative content of the fatty acids 14:0, 15:0, and 17 : 0 in serum PL and AT (r ranging between 0.32 and 0.55). When these fatty acids were correlated to SAD, inverse associations were seen except for 14:0 in PL (r ranging between -0.17 and -0.29. CONCLUSION: If there is a true inverse association between the intake of dairy fat and SAD, it remains to explain why this association was not seen in the non-URs. The data gave some indications of an inverse association between SAD and the intake of calcium. The diverse findings observed when the URs and non-URs were separated highlight the question of how to use and interpret dietary data in URs when diet-disease relationships are investigated.

Adipose Tissue↗

PubMed2004

Office blood pressure underestimates ambulatory blood pressure in peripheral arterial disease in comparison to healthy controls.

Patients with peripheral arterial disease (PAD) constitute a subgroup of high-risk hypertensives, but controlled studies on 24-h blood pressure (BP) and diurnal variation of BP are lacking. This study was performed in order to test the hypothesis that office BP (OBP) may underestimate 24-h BP in PAD patients in comparison to a matched control group. In all, 98 male patients (mean age 68 years) with a history of intermittent claudication and an ankle/brachial index less than 0.9, and 94 controls matched for age but without PAD or ischaemic heart disease performed 24-h recordings of ambulatory BP. A total of 59 patients had a history of hypertension and 69 were on treatment with BP-lowering drugs as compared to 17 and 23 of the control subjects, respectively. Office as well as 24-h systolic BP (SBP) were higher in patients as compared to controls (151 +/- 22 vs 140 +/- 20 mmHg, P < 0.001 and 142 +/- 14 vs 133 +/- 15 mmHg, P < 0.001, respectively), but did not differ with regard to diastolic BP. In an analysis of covariance with the continuous factors age, office SBP and the categorical factor antihypertensive treatment, 24-h SBP was higher in PAD patients compared to controls (P < 0.05). The difference between office and night SBP was lower in PAD patients with antihypertensive treatment compared to controls (P = 0.01). In conclusion, Male patients with PAD had higher systolic but not diastolic BP than age-matched control subjects. In PAD patients, 24-h SBP was higher than expected from OBP compared to controls. Night SBP was higher only in patients with antihypertensive treatment. In PAD patients, especially when on antihypertensive treatment, the severity of hypertension may be underestimated when based on OBP only.

Aged↗

PubMed2003

TNF-alpha: a link between hypertriglyceridaemia and inflammation in SLE patients with cardiovascular disease.

Patients with systemic lupus erythematosus (SLE) are at high risk of cardiovascular disease (CVD). Tumour necrosis factor-alpha (TNF-alpha) has been implicated in the pathophysiological processes of both SLE and CVD. This study focuses on the role of TNF-alpha and its soluble receptors in SLE-related CVD. In summary, 26 women (52 +/- 8.2 years) with SLE and a history of CVD (SLE cases) we compared with 26 age-matched women with SLE and no clinical manifestations of CVD (SLE controls) and 26 age-matched population-based control women (population controls). Plasma concentrations of circulating TNF-alpha, TNF-alpha receptor 1 (sTNFR1) and TNF-a receptor 2 (sTNFR2) were determined by ELISA. TNF-alpha, sTNFR1 and sTNFR2 were raised in SLE cases as compared to SLE controls (P = 0.009; P = 0.001; P = 0.001, respectively), and SLE controls had higher levels than population controls (P = 0.001; P = 0.02; P = 0.001, respectively). Exclusively in the SLE case group there was a striking positive correlation between TNF-alpha and plasma triglycerides (r = 0.57, P < 0.002), VLDL triglycerides (r = 0.54, P = 0.004) and VLDL cholesterol (r = 0.58, P = 0.002). Furthermore, TNF-alpha correlated with the waist-hip ratio but not with estimated insulin resistance. TNF-alpha may thus be a major factor in SLE-related CVD acting both by contributing to hypertriglyceridaemia and by promoting atherosclerosis-related inflammation. sTNFR1 and sTNFR2 are strongly associated with CVD in SLE but their exact roles in disease development remain to be elucidated.

Autoantibodies↗

PubMed2002

Plasma tumour necrosis factor-alpha and early carotid atherosclerosis in healthy middle-aged men.

AIMS: Tumour necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine, which is implicated in some metabolic disorders and may play a role in the development of cardiovascular disease. We examined whether plasma TNF-alpha is related to established cardiovascular risk indicators, plasma levels of soluble cellular adhesion molecules and carotid artery intima-media thickness determined by ultrasound examination in a population-based cohort of 96 healthy 50-year-old men. METHODS AND RESULTS: TNF-alpha and cellular adhesion molecules were measured with enzyme-linked immunosorbent assays. Plasma TNF-alpha concentration was associated with systolic and diastolic blood pressure, degrees of alimentary lipaemia, plasma very low density lipoprotein triglyceride, low density lipoprotein (LDL) cholesterol concentrations and peak LDL particle size. Two indices of insulin resistance as well as all soluble cellular adhesion molecules correlated positively with TNF-alpha. The plasma TNF-alpha concentration was associated with common carotid intima-media thickness in univariate analysis. In contrast, soluble E-selectin and postprandial triglycerides, but not TNF-alpha, were independent determinants of common carotid intima--media thickness. CONCLUSION: The plasma TNF-alpha concentration is associated with degrees of early atherosclerosis and correlates with metabolic and cellular perturbations that are considered important for the vascular process.

ATPases Associated with Diverse Cellular Activitie↗

PubMed2002

Cardiac valvular abnormalities are frequent in systemic lupus erythematosus patients with manifest arterial disease.

The objective of this study was to study cardiac valve morphology and function and ventricular function in systemic lupus erythematosus (SLE) patients with and without co-existing cardiovascular disease (CVD) and in population controls. Twenty-six women (52 +/- 8.2 years) with SLE (SLE cases) and a history of CVD (angina pectoris, myocardial infarction, cerebral infarction or intermittent claudication) were compared with 26age-matched women with SLE but without manifest CVD (SLE controls) and 26 age-matched control women (population controls). Echocardiographywas performed to assess valvular abnormalities and manifestations of ischaemic heart disease. Thirteen of the 26 SLE cases but only one of the SLE controls and one of the population controls had cardiac valvular abnormalities. Three of the SLE cases had already undergone valve replacement and another had significant aortic insufficiency; the other nine had thickening of mainly mitral leaflets without hemodynamic significance. Among SLE cases, patients with valvular abnormalities had higher homocysteine (P < 0.001) and triglyceride (P = 0.02) concentrations than patients without valvular disease. In contrast atherosclerosis as determined by IMT, oxidized LDL as measured by the monoclonal antibody E06, autoantibodies against epitopes of OxLDL (aOxLDL) or phospholipids (aPL), disease duration or activity, or acute phase reactants did not differ between SLE cases with or without valvular abnormalities. Valvular abnormalities were not more common in SLE cases with stroke as compared to those with myocardial infarction, angina or claudication. In conclusion, valvular abnormalities are strongly associated with CVD in SLE. Raised levels of homocysteine and triglycerides characterize patients with cardiac valve abnormalities.

Acute-Phase Reaction↗

PubMed2001

Comparative effects of ramipril on ambulatory and office blood pressures: a HOPE Substudy.

In the HOPE-trial, the ACE inhibitor ramipril significantly reduced cardiovascular morbidity and mortality in patients at high risk for cardiovascular events. The benefit could only partly be attributed to the modest mean reduction of office blood pressure (OBP) during the study period (3/2 mm Hg). However, because according to the HOPE protocol ramipril was given once daily at bedtime and blood pressure was measured during the day, the 24-hour reduction of blood pressure may be underestimated based on OBP. Thirty-eight patients with peripheral arterial disease enrolled in the HOPE study underwent 24-hour ambulatory blood pressure (ABP) measurement before randomization and after 1 year. OBP was measured in the sitting position immediately before fitting the ABP measuring equipment to the patients. Ramipril did not significantly reduce OBP (8/2 mm Hg, P=NS) or day ABP (6/2 mm Hg, P=NS) after 1 year. Twenty-four-hour ABP was significantly reduced (10/4 mm Hg, P=0.03), mainly because of a more pronounced blood pressure lowering effect during nighttime (17/8 mm Hg, P<0.001). The night/day ratio was also significantly lowered in the ramipril group. ABP shows greater falls, especially at night, than OBP during treatment with ramipril given once daily at bedtime. Although, OBP is the correct comparator when comparing with previous large intervention trials and epidemiological studies, the effects on cardiovascular morbidity and mortality seen with ramipril in the HOPE study may, to a larger extent than previously ascribed, relate to effects on blood pressure patterns over the 24-hour period.

Aged↗

PubMed2001

Risk factors for cardiovascular disease in systemic lupus erythematosus.

BACKGROUND: Cardiovascular disease (CVD) is overrepresented in patients with systemic lupus erythematosus (SLE). We determined the prevalence of traditional and nontraditional risk factors for CVD in SLE patients with and without CVD compared with controls. METHODS AND RESULTS: Twenty-six women (aged 52+/-8.2 years) with SLE and a history of CVD (SLE cases) were compared with 26 age-matched women with SLE but without manifest CVD (SLE controls) and 26 age-matched population-based control women (population controls). Common carotid intima-media thickness (IMT) was measured by B-mode ultrasound as a surrogate measure of atherosclerosis. SLE cases had increased IMT compared with SLE controls (P=0.03) and population controls (P=0.001), whereas IMT of SLE controls did not differ from population controls. SLE cases had raised plasma concentrations of circulating oxidized LDL (OxLDL; P=0.03), as measured by the monoclonal antibody EO6, and autoantibodies to epitopes of OxLDL (P<0.001); dyslipidemia with raised triglycerides (P<0.001) and lipoprotein(a) (P=0.002) and decreased HDL-cholesterol concentrations (P=0.03); raised alpha-1-antitrypsin (P=0.002), lupus anticoagulant (P=0.007), and homocysteine levels (P=0.03); more frequent osteoporosis (P=0.03); and a higher cumulative prednisolone dose (P=0.05) compared with SLE controls. Disease duration, smoking, blood pressure, body mass index, and diabetes mellitus did not differ significantly between the groups. CONCLUSIONS: alpha set of distinct CVD risk factors separate SLE cases from SLE controls and population controls. If confirmed in a prospective study, they could be used to identify SLE patients at high risk for CVD in order to optimize treatment.

Autoantibodies↗

PubMed2001

Human evidence that the apolipoprotein a-II gene is implicated in visceral fat accumulation and metabolism of triglyceride-rich lipoproteins.

BACKGROUND: Apolipoprotein (apo) A-II is a major structural protein of plasma HDLs, but little is known regarding its functions. METHODS AND RESULTS: To investigate the physiological role of apoA-II in humans, we screened the promoter region of the apoA-II gene for a functional polymorphism and used this polymorphism as a tool in association studies. A common, functional polymorphism in the promoter region of the apoA-II gene, a T to C substitution at position -265, was found. Electrophoretic mobility shift assays demonstrated that the -265T/C polymorphism influences the binding of nuclear proteins, whereas transient transfection studies in human hepatoma cells showed a reduced basal rate of transcription of the -265C allele compared with the -265T allele. The -265C allele was associated with decreased plasma apoA-II concentration and decreased waist circumference in healthy 50-year-old men. In addition, oral fat tolerance tests provided evidence that the -265C allele enhances postprandial metabolism of large VLDLs. CONCLUSIONS: ApoA-II appears to promote visceral fat accumulation and impair metabolism of large VLDLs.

Adipose Tissue↗

PubMed2001

Relation between drug treatment and cancer in hypertensives in the Swedish Trial in Old Patients with Hypertension 2: a 5-year, prospective, randomised, controlled trial.

BACKGROUND: Is cancer related to hypertension and blood pressure? Do antihypertensive drugs promote cancer? Do antihypertensive drugs protect against cancer? We previously analysed the frequency of cardiovascular mortality and morbidity in elderly people who participated in the Swedish Trial in Old Patients with Hypertension 2 (STOP-Hypertension-2). We have also looked at the frequency of cancer in these patients. METHODS: We randomly assigned 6614 elderly patients with hypertension (mean age 76 years, median time of follow-up 5.3 years) to one of three treatment strategies: conventional drugs (diuretics or b-blockers), calcium antagonists, or ACE inhibitors. We matched the patients to the Swedish Cancer Registry and compared our findings with expected values based on age, sex, and calendar-year-specific reference frequencies for the general Swedish population. We also compared the number of cancers between the three treatment groups. FINDINGS: At baseline, 607 (9%) patients had previous malignant disease. Diagnoses were closely similar to the distribution of cancer types that might be seen in elderly patients. During follow-up, there were 625 new cases of cancer in 590 patients. The frequency of cancer did not differ significantly between the treatment strategies, including all cancers and those at individual sites. The standardised incidence ratios (SIRs) for all cancers were also close to unity: 0.92 (95% CI 0.80-1.06) for conventional drugs, 0.96 (0.83-1.10) for calcium antagonists, and 0.99 (0.86-1.13) for ACE inhibitors. INTERPRETATIONS: No difference in cancer risk was seen between patients randomly assigned to conventional drugs, calcium antagonists, or ACE inhibitors. Thus, the general message to the practising physician is that more attention should be given to getting the blood pressure down than to the risk of cancer.

Aged↗

PubMed2001

Variation in genetic and environmental influences in serum lipid and apolipoprotein levels across the lifespan in Swedish male and female twins.

The contribution of genetic and environmental factors to variation in lipids and apolipoproteins has been estimated in previous twin and family studies. However, it is unclear whether there are sex and/or age differences in parameter estimates. We investigated a sample selected from the population-based Swedish Twin Registry of 725 like- and unlike-sex twin pairs, ages 17-85. Quantitative genetic methods were used to evaluate sex and age differences in genetic and environmental variation in lipid and apolipoprotein levels in three age groups, 17-49, 50-69, and 70-85. Heritabilities for lipids and apolipoproteins ranged from 35%-74%. Consistent sex differences were found in triglycerides. Females had higher heritabilities (56%) than males (35%) across the age groups. Total phenotypic variation increased across the age groups for cholesterol and apolipoprotein B due to an increase in unique environmental variance components. In contrast, in apolipoprotein A1 variance was highest in the middle age group and no differences were found in the phenotypic variance between age groups for triglycerides. We concluded that differences in phenotypic variation for cholesterol and apolipoprotein B were almost entirely due to the accumulation of environmental experiences throughout life, whereas there were no consistent patterns of differences in phenotypic variance for apolipoprotein A1 and triglycerides.

Adolescent↗

PubMed2001

Birthweight, early environment, and genetics: a study of twins discordant for acute myocardial infarction.

BACKGROUND: Epidemiological studies that used birthweight as a crude marker of fetal growth have suggested that low birthweight is associated with increased risk of coronary heart disease. Through investigation of this association within same-sexed twin pairs, confounding by genetic and early environmental factors can be greatly decreased. We undertook a case-control study in twins discordant for acute myocardial infarction (AMI). METHODS: The case-control study was nested within the population-based Swedish Twin Registry and linked with the national cause-of-death and hospital-discharge registries. We manually retrieved birth records containing information on birth and maternal characteristics for 132 same-sexed twin pairs discordant for AMI and 118 individually matched control twin pairs. FINDINGS: In comparisons between AMI cases and external matched control twins, cases had significantly lower birthweight (mean 2556 [SD 500] vs 2699 [530] g, p=0.04), birth length (47.1 [2.8] vs 47.9 [2.7] cm, p=0.04), and head circumference (33.0 [1.8] vs 33.5 [2.0] cm, p=0.03) than controls. In within-pair comparisons between AMI cases and healthy co-twins, no significant differences in birth measurements were found (birthweight 2458 [510] vs 2534 [530] g, p=0.73; birth length 47.1 [2.8] vs 47.2 [2.8] cm, p=0.91; head circumference 33.0 [1.7] vs 33.0 [1.8] cm, p=0.92). INTERPRETATION: The lack of an association between birth characteristics and AMI within twin pairs suggests that previously reported associations may be influenced by genetic and early environmental factors, or possibly, by unmeasured maternal factors that operate independently of birthweight.

Birth Weight↗

PubMed2001

Oxidative stress, human genetic variation, and disease.

Oxidative stress has been implicated in numerous pathophysiological conditions and also aging. The tools for studying oxidative stress are now expanding as a result of the human genome effort and, in particular, expanding knowledge on human genetic variation. A few genetic variants, mostly in the form of single nucleotide polymorphisms of relevance to oxidative stress are already studied by a molecular epidemiologic approach. A review of the current knowledge on variant human genes that are directly implicated in human protection against oxidative stress is presented.

Animals↗

PubMed2001

A common functional C-T substitution polymorphism in the promoter region of the human catalase gene influences transcription factor binding, reporter gene transcription and is correlated to blood catalase levels.

Oxidative stress is implicated in disease and aging. In order to obtain molecular genetic tools that can be used to determine the potential impact of oxidative stress we examined the human catalase gene promoter for possible variation. Genomic DNA isolated from 10 individuals was screened for polymorphisms in the 5'-flanking region by direct sequence analysis of PCR products (nt -307 to -46 from the transcription start site). A common C/T polymorphism -262 base pairs from the transcription start site was detected. Computer analysis indicated that the two variants bound different transcription factors. Indeed, gel retardation analysis revealed different protein binding patterns to the two variants. Expression studies with reporter constructs showed significantly higher transcriptional activity of the T variant in HepG2 and K562 cells (1.5-fold,p <.05 Wilcoxon test). Thus a higher expression in human liver and blood cells is possible. In order to test this hypothesis, catalase levels in red blood cells were determined in 29 donors. The corresponding genotype was determined with a restriction enzyme-based assay. It was found that catalase levels were significantly higher in donors carrying the T allele in comparison to donors homozygous for the C allele (p <.03). In conclusion, we report here the first common (allele frequency in a Swedish population, 28%) genetic variant in a fundamental oxidative stress protection gene with a defined phenotype.

Alleles↗