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Biomedical subjects

M Koskenvuo

Publications and source records attributed to M Koskenvuo.

At least 181 records · Page 10Linked to original sources

Cigarette smoking as a cause of lung cancer and coronary heart disease. A study of smoking-discordant twin pairs.

Despite increasing scientific evidence for a causal role of tobacco smoking in lung cancer and coronary heart disease, an alternative hypothesis was put forward several decades ago. The constitutional hypothesis has stated that there are genetic or other common factors, which predispose both to smoking and disease. A critical test of this hypothesis was considered the pattern of occurrence of disease in monozygotic (MZ) twin pairs in which one is a smoker and the other never has been a smoker. Initial twin studies found only small differences in the mortality of smoking and nonsmoking twins of discordant pairs. In the Finnish Twin Cohort, a population-based panel of adult like-sexed twin pairs, a questionnaire study carried out in 1975 permitted identification of 2488 twin pairs discordant for cigarette smoking. Analyses of total mortality and mortality due to coronary heart disease and lung cancer indicate that the smoking members of discordant MZ pairs are at higher risk than their nonsmoking cotwins; increased mortality of smoking cotwins was also found on 21-year follow-up of smoking-discordant pairs in Sweden. Incidence data and noninvasive studies of atherosclerosis in the Finnish sample provide confirmatory evidence for the causal role of smoking in the etiology of coronary heart disease and lung cancer.

Cohort Studies↗

Study of gene-environment effects on development of hyperopia: a study of 191 adult twin pairs from the Finnish Twin Cohort Study.

The Finnish Twin Cohort material was used to estimate genetic and environmental effects in the etiology of hyperopia (farsightedness). All twin pairs in the cohort born before year 1927 (age 60 years and over at the time of the study), with both members alive, were sent a questionnaire. The questionnaire included questions of past and present eye diseases, visits to ophthalmologists, use of glasses and other vision-related questions. The hyperopia was assessed by asking the patients to send their last prescription for glasses to the authors. Twins with any eye disease affecting refraction (cataract, corneal damage), operation or trauma to their eyes were discarded from the present study. In 191 pairs (80 monozygotic and 111 dizygotic pairs) one or both members of the pair had a hyperopic refractive error. The correlations of refraction between right and left eyes of both MZ and DZ pairs were high (Spearman Rank Correlations of 0.86-0.89). The intrapair correlations among MZ pairs were higher (0.44 for right and 0.45 for left eyes) than intrapair correlations among DZ pairs (0.24 for right and 0.15 for left eyes). The variances were not significantly different among MZ and DZ pairs. The classical analysis of heritability gave an estimate of 0.75 for hyperopia. The result suggests that genetic factors are important in hyperopia and especially in hyperopia of higher degree.

Adult↗

MS and SLE in twins of successive generations.

During a nationwide twin study on multiple sclerosis (MS) in Finland a dizygotic pair discordant for MS was found. The affected co-twin had dizygotic twin daughters. The affected co-twin of the second generation had systemic lupus erythematosus (SLE). Both pairs were thoroughly examined. No evidence of CNS involvement in the healthy co-twins was found. In pairwise comparisons, virus-specific IgG antibodies to measles and mumps were significantly increased in the MS patient whereas the same was true for rubella in the SLE patient. Both MS and SLE patient expressed HLA alleles most often found to be associated with these disorders. Reversed CD4/CD8 ratios were observed in both MS and SLE patient. No difference in interleukin-2 receptor expression were found but gamma-interferon secretion in the MS patient showed marked increase whereas that of the SLE patient was of the same magnitude as in the healthy members. A different triggering stimulus rather than the dissimilarity in the immunogenetic predisposition may be decisive as to whether or not they develop MS or SLE.

Adult↗

Serum selenium concentration, glutathione peroxidase activity and lipid peroxides in a co-twin control study on multiple sclerosis.

Serum selenium concentration, glutathione peroxidase activity and lipid peroxides were determined in patients with multiple sclerosis (MS). The series consisted of 13 same-sexed twin pairs derived from the Finnish Twin Cohort of 15,815 pairs. Fourteen subjects had a definite and 1 a probable MS, and their 11 co-twins showed no evidence of central nervous system disease. No statistical differences were observed, but the 3 patients with active progressive MS had a higher mean level of lipid peroxides than the rest of the patients. We suggest that serum lipid peroxidation may be involved in the activity of MS.

Adult↗

Twins, smoking and mortality: a 12-year prospective study of smoking-discordant twin pairs.

Despite the increasing scientific evidence for a causal role of tobacco smoking in lung cancer and coronary heart disease, critics, several decades ago, put forward an alternative hypothesis. The constitutional hypothesis has stated that there are genetic or other common factors, which predispose both to smoking and disease, but that the two are not causally related. A critical test of this hypothesis is the study of disease in monozygotic (MZ) twin pairs in which one smokes and the other never has. Earlier twin studies found only small differences in the mortality of smoking and nonsmoking twins of discordant pairs. In the Finnish Twin Cohort, a population-based panel of adult like-sexed twin pairs, a questionnaire study carried in 1975 permitted identification of twin pairs discordant for cigarette smoking. The nonsmoking cotwins had never been regular smokers. The smoking twins were divided into 1278 current smokers [CS; 143 MZ and 598 dizygotic (DZ) males and 171 MZ and 585 DZ females] and 1210 former smokers (FS; 129 MZ and 408 DZ males and 113 MZ and 341 DZ females). Exposure to tobacco was much higher among males; over 25% of men smoked 20 or more cigarettes daily compared to less than 10% of women. Follow-up of mortality yielded data on time and cause of death. Analyzing on first deaths from concordant pairs, there were 13 deaths in the smokers of male CS MZ pairs and 1 death in the nonsmoking cotwins (relative risk = 13.0, P less than 0.01). Excess mortality was also found for male CS DZ smokers (RR = 2.43, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Genetic and environmental effects on oculometric traits.

Twenty twin pairs (9 monozygotic and 11 dizygotic) were examined to test the effect of genetic and environmental factors on the etiology of refractive error, axial length of the eyeball, and total astigmatism. The twins pairs were ascertained from the nationwide Finnish Twin Cohort Study (FTCS). The monozygosity was confirmed for nine pairs by a blood group analysis adopted for paternity testing procedures. The mean ages of the monozygotic twin pairs was 69 years and of the dizygotic twin pairs 63 years. Spherical equivalent of refractive error and axial length of the eyeball showed higher intrapair correlations among monozygotic pairs than among dizygotic pairs. This suggests, at least in part, a genetic etiology of these traits. Total astigmatism measured by retinoscopy did not show a significant difference in intrapair correlations between monozygotic and dizygotic twin pairs.

Aged↗

Biliary lipid composition in monozygotic and dizygotic pairs of twins.

The relative contribution of genetic factors to biliary and serum lipid composition was studied in 17 monozygotic and 18 dizygotic middle aged male pairs of twins. Cholesterol precursors, squalene and Methylated sterols which reflect the activity of cholesterol synthesis were also measured. Pairwise intraclass correlations were determined for monozygotic and dizygotic twin pairs and heritability estimates were calculated. Molar % of biliary cholesterol and percentage distribution of biliary cholic acid and particularly deoxycholic acid showed significant pairwise correlations within the monozygotic but not the dizygotic pairs. Similar correlations were found for total biliary methylsterols and of the methylsterol subfractions for the two methostenols but not for squalene, lanosterol and dimethylsterols. In serum, the precursor sterols, but not squalene, showed even higher pairwise correlations in the monozygotic twins than the corresponding precursors in bile. Molar per cent of bile acids and phospholipids and cholesterol saturation index were not correlated significantly in either twin pairs, but the pairwise correlations tended to be higher in the monozygotic than in the dizygotic pairs. Gall stones were found in seven monozygotic and three dizygotic subjects. Two monozygotic twin pairs were concordant for gall stones; all the dizygotic pairs were discordant. Overall, these data suggest that molar percentage of biliary cholesterol, bile acid composition, cholesterol synthesis, bile cholesterol saturation, and gall stone formation may be under a significant genetic control.

Adult↗

Multiple sclerosis and occupational exposure to chemicals: a co-twin control study of a nationwide series of twins.

From the Finnish Twin Cohort (n = 27,100 pairs with known zygosity) all cases of diagnosed multiple sclerosis (MS) were reviewed and those with clinically verified MS were invited for further examinations at the Institute of Occupational Health, Helsinki, with their co-twins. Twenty one cases (19 pairs, of which 17 were discordant) fulfilled the strict criteria of MS. Detailed occupational history showed exposure to a mixture of solvents in six subjects, to lead in one, and to trichloroethylene in one. Of these seven, two monozygotic twins had MS whereas the other five cases were healthy co-twins. These results do not support a causal association between occupational exposure to chemicals and the aetiopathogenesis of MS.

Adult↗

Carotid arteriosclerosis in identical twins discordant for cigarette smoking.

From a nationwide twin panel, identical twin pairs with highest discordance in cigarette smoking were selected for a study of arteriosclerosis (49 pairs with a mean age of 52 years). Smoking history was obtained in 1975, 1981, and 1986. The mean life-long smoking dose of the smoking cotwins was 20 package-years. The smoking and nonsmoking cotwins had similar systolic and diastolic blood pressures, total plasma cholesterol level, body mass index, and some psychosocial factors; the only difference was found in use of alcohol, which was greater among smoking cotwins. Duplex sonography of carotid arteries was performed. Carotid artery stenoses (narrowing of area of the lumen with 15-60%) were found in nine pairs: in nine smoking twins and in two of their nonsmoking cotwins (p = 0.036). The total area of carotid plaques was 3.2 times larger in smoking cotwins (p less than 0.001). The thickness of the inner layer of carotid arteries was more marked in smoking cotwins (p less than 0.001). The size of plaques and the degree of inner layer thickening correlated with the dose of smoking (NS). The association of smoking with carotid arteriosclerosis was highly significant even after the adjustment for age, total plasma cholesterol level, diastolic blood pressure, and body mass index in multiple logistic regression analyses.

Carotid Arteries↗

Genetic and environmental factors in sciatica. Evidence from a nationwide panel of 9365 adult twin pairs.

The relative roles of genetic and environmental factors in sciatica were studied in the nationwide Finnish twin panel consisting of 9365 adult pairs of the same gender. Morbidity was analysed from two sources of data: the life-long cumulative incidence was measured by a postal questionnaire, and the rate of hospital admission during a 14-year period was measured by record-linkage of the twin panel and the nationwide hospital registry. Altogether 2220 individuals reported sciatica diagnosed by a doctor and 304 were admitted to hospital with a diagnosis of sciatica. The proportion of concordant pairs (calculated from affected pairs) was 17.7% for monozygotic and 12.0% for dizygotic pairs in the life-long cumulative incidence of reported sciatica, and correspondingly 4.6% and 1.9% for those admitted to hospital (a 14-year period) because of sciatica. The estimated heritability was 20.8% for those with reported sciatica and 10.6% for those admitted to hospital. The results show that environmental factors account for more than 80% of the etiology of sciatica, and more than 90% in the case of patients admitted to the hospital. Genetic factors, however, were relatively more significant in individuals under 40.

Adult↗

Vasoactive and atherogenic effects of cigarette smoking: a study of monozygotic twins discordant for smoking.

The mechanism by which atherosclerotic disease is induced by cigarette smoking has not yet been identified unequivocally. Chronic cigarette smoking and the generation of vasoactive prostanoids and the size of carotid atherosclerotic plaques were studied in nine pairs of identical male twins discordant for smoking for over 20 years. The urinary excretion of 2,3-dinor-thromboxane B2 (thromboxane B2 metabolite) of the smoking twin was significantly higher (on average 1.8 times higher) in every pair and that of 2,3-dinor-6-keto-prostaglandin F1 alpha (prostacyclin metabolite) was significantly higher (on average 1.3 times higher) in eight of the nine pairs. The ratio of excretion of these metabolites was significantly higher, being 4.0 (95% confidence interval 2.7 to 5.4) among the smokers compared with 2.9 (2.1 to 3.8) among the non-smokers, thus favouring a mechanism of vasoconstriction. Excretion of the thromboxane B2 metabolite was related to the urinary concentrations of nicotine metabolites. Atherosclerotic plaques detected by ultrasonography in the carotid arteries were significantly larger among smokers but did not correlate with the urinary excretion of prostacyclin and thromboxane B2 metabolites or intensity of smoking. Smoking was concluded to induce activation of platelets by an effect mediated by nicotine. The increased prostacyclin production, on the other hand, suggested a compensatory mechanism for the general vasoconstrictive properties of cigarette smoking.

6-Ketoprostaglandin F1 alpha↗

Genetic susceptibility to multiple sclerosis. A co-twin study of a nationwide series.

The problems of differentiation between environmental and genetic influences on the development of multiple sclerosis are well known. Twin studies may provide valuable information on this question. However, most published twin series are selected and no through clinical twin studies based on epidemiologic series have been carried out. In this study, all available same-sex twin pairs with clinically definite multiple sclerosis derived from the Finnish Twin Cohort of 15815 pairs were studied by clinical evaluation, magnetic resonance imaging, and visual and auditory evoked responses. The mean length of follow-up of the pairs after the onset of symptoms of multiple sclerosis was 20 years. Two of the seven monozygotic pairs were concordant; one was definitely so, and in the other, the co-twin of the index case had, in addition to clinical findings, white matter changes suggestive of multiple sclerosis in magnetic resonance imaging and abnormal visual evoked responses. All six dizygotic pairs were discordant. The frequency of the HLA antigen DR2 in probands (69%) was significantly increased, but the distribution among the healthy subjects and patients showed nonsignificant differences. The results indicate a genetic influence on the susceptibility to multiple sclerosis, although still unknown genetic determinants are possible involved.

Adult↗

A prospective study of psychological and socioeconomic characteristics, health behavior and morbidity in cigarette smokers prior to quitting compared to persistent smokers and non-smokers.

Psychosocial factors influencing smoking cessation were studied in current smokers prior to quitting. Two questionnaires were sent in 1975 and 1981 to adult members of the Finnish Twin Cohort. The 1975 response rate was 89%, and 89% of those eligible replied again in 1981. Analysis was done on data from one twin pair member only. Three groups were identified: 3617 never smokers, 2654 persistent smokers, and 823 quitters (i.e. current smokers in 1975, former smokers in 1981). Univariate and multivariate comparisons of baseline psychosocial variables for quitters and persistent smokers were performed in men aged 20-34 and 35-54 and women aged 20-39. Among women and young men quitters were better educated and scored lower on neuroticism. Young male quitters also slept longer, had been less often unemployed and drank less alcohol and coffee. Among middle-aged men quitters were more often married, slept longer, and had higher life satisfaction. The possibility that the influence of psychosocial factors on chronic disease may be mediated in part through changes in smoking behavior is discussed.

Adult↗

Shared genes, shared experiences, and similarity of personality: data from 14,288 adult Finnish co-twins.

Similarities for Extraversion (E) and Neuroticism (N) scale scores from the Eysenck Personality Inventory were evaluated in 7,144 adult twin pairs, drawn from the population-based Finnish Twin Cohort, as a function of the co-twins' genetic resemblance, gender, age, and the frequency of their social interaction with each other. To separate effects of shared genes from those of shared experience, we performed hierarchical multiple regressions of double-entry data matrices. Results establish the predictive significance of both genetic and experiential influences: Genetic effects remained significant when tested after the effects of social contact were first removed; conversely, for N scores, the effects of social contact remained significant when assessed after genetic influences were first removed. These findings establish genetic variance in major dimensions of adult personality but assign a significant role to common experience as well. The first finding constructively replicates reports by others; the second challenges the widespread assumption that shared experiences have a negligible impact on sibling similarity in adult personality.

Adult↗

Prospective study of asthma in relation to smoking habits among 14,729 adults.

The prevalence and incidence of asthma in relation to cigarette smoking habits was studied in a population of 14,729 Finnish adult men and women who participated in a postal health survey in 1975. Of those invited to participate in a new survey in 1981, 89.7% replied. Asthma was diagnosed on the basis of self reporting of asthma diagnosed by a physician and by record linkage to a national register of hospital admissions to all general and tuberculosis hospitals during 1972 and 1983. The prevalence of diagnosed asthma in 1975 was significantly higher among male smokers than among male non-smokers (relative risk (RR) = 1.73); no significant difference was observed for women (RR = 1.33). People with asthma were slightly but not significantly more likely to stop smoking during the six year follow up period (RR = 1.23). The incidence of asthma among those who had neither reported asthma in 1975 nor been admitted to hospital for asthma before the 1975 questionnaire study was not significantly higher among smokers than among non-smokers during follow up. Although possible mechanisms exist to explain how smoking could have a role in the aetiology of asthma, this study suggests that smoking is not a strong risk factor for asthma.

Adult↗

Decreased beta-adrenergic receptor density and catecholamine response in male cigarette smokers. A study of monozygotic twin pairs discordant for smoking.

The effect of long-term cigarette smoking on beta-adrenoceptor density and catecholamine response was studied in 10 monozygotic male twin-pairs discordant for smoking, with an average discordance time for smoking of 23 years (range, 12-35 years). The density of beta-adrenergic receptors was 40% lower in the lymphocytes of smoking twins compared with their nonsmoking cotwins (beta-receptor density, 6.7 +/- 1.2 and 11.1 +/- 1.8 fmol/10(6) cells, respectively; p less than 0.05). The corresponding apparent Kd values were 31.7 +/- 5.5 and 26.7 +/- 5.4 pM, respectively. Stimulation of the lymphocyte beta-receptors resulted in significantly lower levels of cyclic adenosine monophosphate in the smokers compared with the nonsmokers (16.2 +/- 3.3 vs. 29.2 +/- 6.5 pmol/10(6) cells, p less than 0.05). When subjected to submaximal exercise, the smokers had a lower level of cyclic adenosine monophosphate in plasma (25.9 +/- 1.2 vs. 28.6 +/- 1.0, p less than 0.05) and a net decrease was seen in plasma free fatty acids in the smokers compared with a net increase in the nonsmokers (-15% vs. +19%, p less than 0.01). The total plasma catecholamine level was, in the basal state, significantly higher in smokers compared with nonsmokers (74.8%, p less than 0.05). The intrapair difference in plasma norepinephrine predicted well the intrapair difference in beta-receptor density (r = -0.84, p less than 0.001). We conclude that the autonomic neurohumoral response evoked by cigarette smoking results in downregulation of beta-adrenergic receptors in long-term smokers.

Adult↗

Parkinson's disease in a nationwide twin cohort.

The Finnish Twin Cohort includes all Finnish same-sexed twins born before 1958 and alive in 1967; the number of individuals alive in 1975 was 33,247. We performed a search for cases with Parkinson's disease among this cohort by linking the Twin Cohort Register with the Finnish Hospital Discharge Register and the Finnish Sickness Insurance Register. We ascertained altogether 42 cases of Parkinson's disease occurring in 41 twin including 18 monozygotic pairs, 14 dizygotic pairs, and nine pairs of undetermined zygosity. Only one dizygotic pair was concordant for Parkinson's disease; all other pairs were discordant. In 1981, the expected number of cases among the Twin Cohort, calculated according to the age- and sex-specific prevalence rates of Parkinson's disease in Finland, was 33. At the same time, the observed number of patients alive was 35. This study, further substantiating the low concordance for Parkinson's disease in monozygotic as well as in dizygotic twins and indicating that the prevalence of Parkinson's disease in twins compares with the prevalence in the general population, suggests that Parkinson's disease is an acquired disease not caused by a hereditary process.

Aged↗