Biomedical subjects

M Koskenvuo

Publications and source records attributed to M Koskenvuo.

At least 91 records · Page 5Linked to original sources

PubMed1999

Breast cancer risk in monozygotic and dizygotic female twins: a 20-year population-based cohort study in Finland from 1976 to 1995.

This population-based study investigated the occurrence of breast cancer over a 20-year period in a cohort of monozygotic (MZ) and dizygotic (DZ) twins in Finland. Altogether, 13,176 female twins of known zygosity who were living in Finland at the end of 1975 were identified from the Finnish Twin Cohort Study and followed-up for cancer through the Finnish Cancer Registry for the years 1976-1995. Standardized incidence ratios (SIRs) were calculated, based on national cancer incidence rates. The relative risk of breast cancer for MZ twins compared to DZ twins was decreased [SIR(MZ)/SIR(DZ) ratio = 0.78; 95% confidence interval (CI), 0.58-1.0]; the decreased risk for MZ twins (SIR = 0.76; 95% CI, 0.58-1.0) accounted for this result, whereas the risk for DZ twins did not differ from the general population risk (SIR = 0.98; 95% CI, 0.84-1.1). There was no risk decrease among MZ twins in other cancers related to reproductive behavior; i.e., number of children and age at first birth seem not to explain the decreased risk of breast cancer. Our results, which are in line with earlier studies on the same topic, suggest that prenatal influences or postnatal behavioral factors may protect MZ female twins from breast cancer.

Adolescent↗

PubMed1998

Intragenic polymorphisms of the vitamin D receptor gene associated with intervertebral disc degeneration.

STUDY DESIGN: A study in genetic epidemiology of disc degeneration, based on lifetime exposure data, findings on magnetic resonance imaging, and genotyping of intragenic markers. OBJECTIVES: To pursue the potential correlation between common allelic variations in the vitamin D receptor locus and degeneration of the intervertebral disc. SUMMARY OF BACKGROUND DATA: Familial aggregation has been observed in intervertebral disc degeneration, but the relative significance of the genetic component and shared environmental influences is unknown. The identification of relevant candidate genes associated with disc degeneration would specify a genetic component and increase our understanding of the etiopathogenesis of disc degeneration. METHODS: From the population-based Finnish Twin cohort, 85 pairs of male monozygotic twins were selected based on exposure to suspected risk factors for disc degeneration. Interview data were gathered on relevant lifetime exposures, and thoracic and lumbar disc degeneration was determined through quantitative and qualitative assessments of signal intensity on magnetic resonance imaging, and qualitative assessments of disc bulging and disc height narrowing. Possible associations were examined between disc degeneration measures and two polymorphisms of the coding region of the vitamin D receptor locus. RESULTS: Two intragenic polymorphisms of the vitamin D receptor gene revealed an association with disc degeneration. Quantitatively assessed signal intensities of thoracic and lumbar (T6-S1) discs were 12.9% worse in men with the Taql tt genotype and 4.5% worse in men with the Tt genotype, compared with signal intensity in men with the TT genotype (age adjusted P = 0.003). A similar pattern was found between disc signal intensity and Fokl genotypes; men with the ff and Ff genotypes had mean signal intensities that were 9.3% and 4.3% lower, respectively, than those in men with FF genotypes (age-adjusted P = 0.006). The summary scores of qualitatively assessed signal intensity, bulging, and disc height were 4.0% and 6.9% worse in men with Ff and ff genotypes, respectively, when compared with those in men with the FF genotype (age-adjusted P = 0.029). CONCLUSION: Specific vitamin D receptor alleles were associated with intervertebral disc degeneration as measured by T2-weighted signal intensity, demonstrating for the first time, the existence of genetic susceptibility to this progressive, age-related degenerative process.

Adult↗

PubMed1998

Nocturnal enuresis in a nationwide twin cohort.

We studied the occurrence of nocturnal enuresis (bedwetting) after the age of 4 years, using a questionnaire in a well-defined population, the Finnish Twin Cohort, which consists of 11,220 subjects aged 33-60 years, including 1298 monozygotic and 2419 dizygotic twin pairs. Structural equation modeling techniques were used to estimate variance components to compare different genetic models. Females reported enuresis in childhood "often" in 3.4% (males in 4.0%) and "sometimes" in 5.7% (8.0%). As adults, females had experienced enuresis "weekly" in 0.3% (males in 0.2%) and "monthly" in 0.07% (0.1%). Those who had experienced enuresis in childhood had had "at least sometimes" enuresis as adults in 5.4% of males and in 5.5% of females. Among those who reported they never had experienced enuresis as adults, 70.8% of males and in 77.9% of females had never experienced enuresis in childhood. For enuresis in childhood, the probandwise concordance rate was 0.43 for monozygotic and 0.19 for dizygotic pairs, and in adults 0.25 and 0, respectively. The proportion of total phenotypic variance attributed to genetic influences (due to dominance) was 67% in males (95% confidence interval 57-76%) and 70% in females (61-78%) in childhood enuresis. In conclusion, nocturnal enuresis is common in childhood and rare in adulthood. Our results confirm the central role of genetic liability in enuresis.

Adult↗

PubMed1998

Lifestyle, stress, and genes in peptic ulcer disease: a nationwide twin cohort study.

BACKGROUND: The familial accumulation of peptic ulcer disease observed in several studies may be attributable to genetic effects, aggregation of environmental exposure (shared environment), or both. The intrafamilial spread of Helicobacter pylori infection has raised the question whether shared environment could explain the familial aggregation of peptic ulcer disease rather than genetic similarity of family members. OBJECTIVE: To examine the contribution of genetic and environmental factors to the pathogenesis of peptic ulcer disease in a nationwide population-based cohort of adult twins. METHODS: The Finnish Twin Cohort consists of all same-sexed twin pairs born before 1958 with both twins alive in 1975. The total number of twin pairs is 13888, of whom 4307 are monozygotic (MZ) and 9581 are dizygotic (DZ) twins. Questionnaire surveys of twins were carried out in 1975, 1981, and 1990, including medical and psychosocial questions. One question asked whether a physician had ever made a diagnosis of gastric or duodenal ulcer. In addition, hospital discharge data from 1972 to 1991 were linked with the twin cohort to obtain those twin individuals who had been treated for gastric or duodenal ulcer. The prevalence of and concordance for peptic ulcer disease were examined in MZ and DZ twins. Model-fitting analysis was used to specify the relative roles of genetic and environmental factors. The contribution of lifestyle factors and stress was examined prospectively in an incidence study and by comparison of discordant pairs. RESULTS: The prevalence of peptic ulcer disease was 6.2% in men and 2.8% in women in 1975. There were 63 MZ and 86 DZ pairs concordant for peptic ulcer disease. Concordance for disease was significantly higher in MZ than in DZ twin pairs; the probandwise concordance rate was 23.6% (95% confidence interval [CI], 20.9%-26.3%) in MZ twins and 14.8% (95% CI, 13.3%-16.3%) in DZ twins. In the model-fitting analysis, a model with both additive genetic and unshared environmental effects had the best goodness-of-fit. Thirty-nine percent (95% CI, 32%-47%) of the liability to peptic ulcer disease was explained by genetic factors and 61% (95% CI, 53%-68%) by individual environmental factors. In the incidence study (logistic regression analysis of the entire cohort initially free of peptic ulcer disease, with subjects diagnosed as having peptic ulcer after 1975 as cases), current smoking (relative risk, 2.2; 95% CI, 1.5-3.2) and high stress levels (relative risk, 3.2; 95% CI, 1.4-7.6) in men and regular use of analgesics (relative risk, 3.3; 95% CI, 1.3-8.1) in women predicted peptic ulcer disease during the follow-up from 1976 to 1991. In the analysis of discordant pairs, smoking in men and regular use of analgesics in both sexes were predictors of peptic ulcer disease. CONCLUSIONS: The questionnaire and hospital usage data on peptic ulcer disease in the population-based twin cohort suggest that the familial aggregation of the disease is modest, and attributable almost solely to genetic factors. Environmental effects not shared by family members were significant predictors of disease, and they were attributable to smoking and stress in men and the use of analgesics in women. The minor effects of shared environment to disease liability do not support the concept that the clustering of risk factors, such as H pylori infection, would explain the familial accumulation of peptic ulcer disease.

Activities of Daily Living↗

PubMed1998

Relationship of leisure-time physical activity and mortality: the Finnish twin cohort.

CONTEXT: Physical activity and fitness are believed to reduce premature mortality, but whether genetic factors modify this effect is not known. OBJECTIVE: To investigate leisure physical activity and mortality with respect to familial aggregation of health habits during childhood and factors that may enable some individuals to achieve higher levels of fitness. DESIGN: Prospective twin cohort study. SETTING: Finland. SUBJECTS: In 1975, at baseline, 7925 healthy men and 7977 healthy women of the Finnish Twin Cohort aged 25 to 64 years who responded to a questionnaire on physical activity habits and known predictors of mortality. Those who reported exercising at least 6 times per month with an intensity corresponding to at least vigorous walking for a mean duration of 30 minutes were classified as conditioning exercisers, those who reported no leisure physical activity were classified as sedentary, and other subjects were classified as occasional exercisers. MAIN OUTCOME MEASURES: All-cause mortality and discordant deaths among same-sex twin pairs from 1977 through 1994. RESULTS: Among the entire cohort, 1253 subjects died. The hazard ratio for death adjusted for age and sex was 0.71 (95% confidence interval [CI], 0.62-0.81) in occasional exercisers and 0.57 (95% CI, 0.45-0.74) in conditioning exercisers, compared with those who were sedentary (Pfor trend <.001). Among the twin pairs who were healthy at baseline and discordant for death (n=434), the odds ratio for death was 0.66 (95% CI, 0.46-0.94) in occasional exercisers and 0.44 (95% CI, 0.23-0.83) in conditioning exercisers compared with those who were sedentary (P for trend, .005). The beneficial effect of physical activity remained after controlling for other predictors of mortality. CONCLUSION: Leisure-time physical activity is associated with reduced mortality, even after genetic and other familial factors are taken into account.

Adult↗

PubMed1998

The genetic epidemiology of schizophrenia in a Finnish twin cohort. A population-based modeling study.

BACKGROUND: The magnitude of heritability of schizophrenia remains controversial, due in part to limitations of estimates derived from index twin pairs exclusively. We applied structural equation modeling in a total population of twins to determine the significance and magnitudes of the genetic and environmental contributions to schizophrenia. METHODS: All monozygotic (1180 male and 1315 female pairs) and same-sex dizygotic (2765 male and 2613 female pairs) twins born from 1940 to 1957 in Finland were screened for nonorganic psychotic disorder diagnoses as recorded on an inpatient or outpatient basis or from an eligibility review for a disability pension. RESULTS: The lifetime prevalence of schizophrenia was 2.0%, with a marginally higher prevalence in men (2.2%) than women (1.8%). Model fitting indicated that 83% of the variance in liability was due to additive genetic factors, and the remaining 17% was due to unique environmental factors. Sex-limitation modeling revealed no evidence of sex-specific genetic effects and no sex difference in the magnitude of heritability. A multiple threshold model incorporating affective and other psychoses as a phenotype intermediate between schizophrenia and no diagnosis was rejected. CONCLUSIONS: In a population-based twin study of schizophrenia, heritability was estimated at 83%, with the remaining variance in liability attributed to environmental factors not shared in common among co-twins. Despite the notable limitation of using diagnoses ascertained through treatment contacts, the heritability estimate in this study is almost identical to those reported in recent studies of index pairs using standardized applications of DSM-III or later criteria.

Adult↗

PubMed1998

Response of hostile individuals to stressful changes in their working lives: test of a psychosocial vulnerability model.

BACKGROUND: According to the psychosocial vulnerability model, the health of hostile individuals is at greater risk than that of non-hostile individuals, due partly to lesser ability of the former to cope with psychosocial stress situations. We examined whether hostile individuals were more vulnerable than others to health problems when faced with stressful changes in their working lives. METHODS: Hostility, sickness absence and psychosocial stressors in 866 local government employees over a 5-year period, which included severe economic decline, were investigated. Hostility was measured by a questionnaire. Data on medically certified sickness absence were obtained from the records of the local authority. Information about exposure to psychosocial stressors after assessment of hostility was also derived from these records, and from the subjects. RESULTS: Exposure to stressors during the period of economic decline was related to increased rates of sickness absence. In men, hostility increased risk of sickness absence after exposure to stressors only in cases of absence because of trauma. In women, hostility increased risk of absence through sickness overall and absence because of musculoskeletal disorders in individuals facing stressors such as severe organizational downsizing, high or increased levels of job demands or negative change in work. Findings were adjusted for sickness absence at the beginning of the decline, socio-economic background and behavioural risk factors. CONCLUSIONS: The psychosocial vulnerability model was partly supported. However, heightened vulnerability through hostility may differ between the sexes, since it was more evident in the women studied than in the men.

Absenteeism↗

PubMed1998

Sleeptalking in twins: epidemiology and psychiatric comorbidity.

Sleeptalking is usually benign but chronic cases in adults may relate to psychopathology. We hypothesize substantial genetic influences in the liability to sleeptalking and an association between sleeptalking and psychiatric disorders. In 1990 a questionnaire sent to the Finnish Twin Cohort yielded responses from 1298 monozygotic and 2419 dizygotic twin pairs aged 33-60 years. We used structural equation modelling to estimate genetic and environmental components of variance in the liability to sleeptalking. Register data on hospitalization and long-term antipsychotic medication were used to assess psychiatric comorbidity. The occurrence of childhood and adult sleeptalking was highly correlated. A gender difference was only seen in adults, with sleeptalking being more common in males than in females. The proportion of total phenotypic variance in liability to sleeptalking attributed to genetic influences in childhood sleeptalking was 54% (95% CI, 44-62%) in males and 51% (43-58%) in females, and for adults it was 37% (27-46%) among males and 48% (40-56%) among females. An association with psychiatric comorbidity was found only in adult sleeptalking, and it was highest in those with adult-onset sleeptalking (odds ratio, 3.77; 95% CI, 2.32-6.17). Sleeptalking is quite a persistent trait, also being common in adults. There are substantial genetic effects on sleeptalking both in childhood and as adults, which appear to be highly correlated. In adults psychiatric comorbidity is about twice as common in those with frequent sleeptalking, compared to those with infrequent or no sleeptalking, but most cases of sleeptalking are not associated with serious psychopathology.

Adult↗

PubMed1998

Hereditary factors in basal cell carcinoma of the skin: a population-based cohort study in twins.

The contribution of hereditary factors in basal cell carcinoma of the skin has not been well defined at the population level. We aimed to assess the hereditary component in basal cell carcinoma by comparing its occurrence in monozygotic and dizygotic twin pairs. The Finnish Twin Cohort, comprising 12,941 adult, like-sex twin pairs with established zygosity and resident in Finland in 1975, was linked with the Finnish Cancer Registry. We identified 335 twin pairs in which at least one twin had basal cell carcinoma diagnosed between 1953 and 1996. Standardized incidence ratios, concordances, tetrachoric correlations and pairwise relative risks were computed by standard methods. Components of variance in liability were estimated by structural equation modelling. There was an elevated risk of basal cell carcinoma for the co-twin of a diseased twin, but no difference in risk by zygosity. During the prospective follow-up in 1976-96, the probandwise concordance was 7.7% in monozygotic and 7.0% in dizygotic pairs. Model fitting indicated that genetic factors were not needed to account for the distribution of basal cell carcinoma in twin pairs. These results confirm the major role of environmental factors in the aetiology of basal cell carcinoma.

Adult↗

PubMed1998

Sleep bruxism based on self-report in a nationwide twin cohort.

The relative roles of genetic and environmental factors in bruxism are not known. In 1990 a questionnaire sent to the Finnish Twin Cohort yielded responses from 1298 monozygotic and 2419 dizygotic twin pairs aged 33-60 years. We used structural equation modelling to estimate genetic and environmental components of variance in the liability to bruxism. There was a significant gender difference both in childhood (P = 0.001) and adult (P = 0.007) bruxism. Females compared to males reported childhood bruxism 'often' 5.2% vs 4.1% and 'sometimes' 17.4% vs 17.3%, and as adults 'weekly' 3.7% vs 3.8% and 'monthly' 3.9% vs 4.6%, respectively. Bruxism in childhood and adulthood is highly correlated (0.86 in males and 0.87 in females). The proportion of total phenotypic variance in liability to bruxism attributed to genetic influences in childhood bruxism was 49% (95% CI 37-60%) in males and 64% (55-71%) in females, and for adults 39% (27-50%) among males and 53% (44-62%) among females. The correlation between the genetic effects on childhood bruxism and the genetic effects on adult bruxism was estimated in a bivariate model to be 0.95 (95% CI 0.94-0.96) in males and 0.89 (0.88-0.90) in females. Bruxism appears to be quite a persistent trait. There are substantial genetic effects on bruxism both in childhood and as adults, which appear to be highly correlated.

Adult↗

PubMed1998

Chlamydia pneumoniae-specific cell-mediated and humoral immunity in healthy people.

In this work, cell-mediated immunity to Chlamydia pneumoniae was studied in 157 healthy individuals using lymphoproliferative assay and serum antibodies were analysed by microimmunofluorescence techniques. The C. pneumoniae-specific IgG antibodies were elevated more frequently and the geometric mean titres for IgG (67.5 versus 44.1; P = 0.05) and IgA (14.9 versus 11.3; P = 0.025) antibodies were significantly higher in males than in females. However, no gender-dependent differences were observed in cellular reactivity to C. pneumoniae, since the median cellular responses were similar (stimulation indices 7.5) in men and women. Although the cell-mediated and humoral responses to C. pneumoniae did not correlate clearly, elevated IgG antibodies were associated with slightly higher lymphocyte proliferation in comparison to all subjects (15.5 versus 7.5) and significantly stronger in comparison to those with persistently elevated IgA (> 80) antibodies (15.5 versus 3.5; P = 0.023). Further studies are needed to evaluate a possible role of reduced cellular reactivity in the cause of chronic C. pneumoniae infection.

Adult↗

PubMed1998

Immune responses to Chlamydia pneumoniae in twins in relation to gender and smoking.

This study investigated whether gender or smoking has an impact on immune responses to Chlamydia pneumoniae in generally healthy adults. A total of 129 twins (46 twin pairs and 37 single twins) from the Finnish Twin Cohort who had previously reported the highest discordance for smoking with their co-twins participated. C. pneumoniae-specific serum IgA and IgG antibody levels were measured by the micro-immunofluorescence test (micro-IF) at admission and 3 months later if the IgA level in the first sample was elevated. Cell-mediated immune (CMI) responses to C. pneumoniae and control antigens from heparinised blood samples were assessed by the lymphoproliferation (LP) assay. When all the subjects were pooled and analysed by gender and smoking status, marked differences in the humoral immune response between the genders were observed, irrespective of smoking status. When twin pairs solely were analysed, significantly elevated IgA antibody levels suggestive of persistent infection were found among the currently or formerly smoking men compared to their non-smoking co-twins. The CMI response showed a reciprocal trend with respect to humoral immunity. In conclusion, specific antibody levels were found to be higher in men than in women irrespective of smoking status, although smoking may further enhance the humoral response and depress the CMI response in men.

Adult↗

PubMed1998

Hay fever--a Finnish nationwide study of adolescent twins and their parents.

BACKGROUND: Like other atopic diseases, hay fever is known to cluster in families. This clustering is due either to effects of a shared family environment or to genetic inheritance. By comparing the occurrence of hay fever among monozygous (MZ) and dizygous (DZ) twin pairs, we were able to estimate the contribution of genetic and environmental factors in the development of hay fever. METHODS: A questionnaire mailed to a nationwide sample of 2483 families with 16-year-old twins furnished data for the cumulative incidence of physician-diagnosed hay fever among these adolescents and their parents. RESULTS: Among the 1765 twin pairs with data available for analysis, hay fever was reported for 14.1% of boys (95% CI=12.4-15.8%) and 10.0% of girls (95% CI=8.6-11.4%). The MZ twin pairs (probandwise concordance rate=60.3%, 95% CI =52-68%) were significantly more concordant for hay fever than were DZ twin pairs (31.5%, 95% CI=26-36%). Genetic factors accounted for 74-82% of the interindividual variability in liability to hay fever, variation in shared family environment for 7% at most, and unique (individual) environment for 18%. CONCLUSIONS: Familial occurrence of hay fever is mainly due to genes predisposing to the trait. Environmental exposures shared in common by family members but varying between families appear to account for at most a modest proportion of the variability in risk of developing hay fever.

Adolescent↗

PubMed1998

Serum lipids and apolipoprotein E phenotypes in identical twins reared apart.

Lipid and lipoprotein metabolism is controlled by genes, the environment and the gene environment interaction. We studied monozygotic twin pairs reared apart (MZA) and an age sex matched group of twins reared together (MZT) to evaluate the effects of the genotype and the rearing environment on lipids. The intraclass correlations for low density lipoprotein (LDL) cholesterol were 0.21 and 0.50 for the MZA and MZT groups, respectively, suggesting that the rearing environment possibly had an impact on the variability in LDL cholesterol later in life. The intraclass correlations for total cholesterol (0.26 and 0.47 for the MZA and MZT groups, respectively) reflected those for LDL cholesterol. The intraclass correlations for high density lipoprotein (HDL) cholesterol did not show any difference between the twin groups, suggesting that the rearing environment does not have major long-term effects on the variability of HDL levels. The intrapair differences for LDL cholesterol were smallest in the twins heterozygous for the apolipoprotein E allele epsilon2 (E2/3 and E2/4 phenotypes), intermediate in the pairs with the common E3/3 phenotype and enhanced in the pairs with E4/3 phenotype. To conclude, these data suggest that the rearing environment may play a role in the variability of LDL cholesterol levels, although variance difference between MZAs and MZTs, and the small number of available monozygotic twins reared apart limits the generalizability of the results.

Apolipoproteins E↗

PubMed1998

Distribution of insulin-dependent diabetes mellitus (IDDM)-related HLA alleles correlates with the difference in IDDM incidence in four populations of the Eastern Baltic region.

The high incidence of insulin-dependent diabetes mellitus (IDDM) in Finland contrasts strikingly with the low rates in the neighbouring populations of countries in the Eastern Baltic region: Estonia, Latvia and Russia. To evaluate the possible contribution of genetic factors to these differences, the frequencies of HLA-DQB1 alleles and relevant DQB1-DQA1 or DQB1-DRB1 haplotypes associated with IDDM risk or protection were analysed among IDDM patients and control subjects from these four populations. An increased frequency of HLA-DQB1*0302, DQB1*02-DQA1*05 and DQB1*0302-DRB1*0401 was observed in subjects with IDDM in all studied populations, whereas the prevalence of DQB1*0301 and DQB1*0602 and/or *0603 was decreased among patients. The degree of IDDM risk associated with HLA alleles analysed here did not differ significantly between the populations. Comparisons of the distribution of IDDM-related HLA alleles and haplotypes in the background populations revealed its consonance with IDDM incidence. The combined frequency of high risk genotypes was significantly higher among Finns than in other populations studied. Our data support the hypothesis that variance in the dispersion of HLA alleles is the genetic basis of variation of IDDM incidence observed in the Eastern Baltic region.

Alleles↗

PubMed1998

Environmental differences in twin pairs discordant for Alzheimer's disease.

The aim of this study was to examine the contribution of environmental factors to the pathogenesis of Alzheimer's disease by comparing environmental differences in twin pairs discordant for Alzheimer's disease. Seventy four twin pairs discordant for Alzheimer's disease were found by linking the Finnish twin cohort and the Hospital Discharge Register from years 1972-91. In 50 pairs (25 monozygotic and 25 dizygotic pairs), both co-twins had responded to a questionnaire survey in 1975. Exposure differences were compared between these pairs. A reduced risk of Alzheimer's disease was significantly associated with a higher level of schooling (relative risk 0.3; 95% confidence interval 0.1-0.9, p=0.029). In addition, a reduced risk was suggestively associated with ambidextrousness or left handedness (p=0.083) and an increased risk with marriage (p=0.052), widowhood (p=0.074), and a history of cholelithiasis (p=0.071). In conclusion, a reduced risk of Alzheimer's disease was associated with a higher level of schooling.

Aged↗

PubMed1998

Importance of genetic factors in adolescent asthma: a population-based twin-family study.

Gene-environment interactions and inheritance of asthma were studied in 16-yr-old twins and their parents who participated in the nationwide Finnish Twin Cohort Study. Between 1991 and 1994, questionnaires, including a question on physician-diagnosed asthma, were mailed to the members of 2,483 twin families. The individual response rate ranged from 82 to 93%. Information on parental asthma status allowed the genetic modeling of asthma data in two different groups of twins. In families where one of the parents was asthmatic, as much as 87% of the variation in susceptibility to asthma in twins was explained by genetic factors. On the other hand, for twins whose parents were unaffected, a model including environmental effect alone was sufficient to explain the development of asthma. Genetic influences could not be totally excluded, but their role was significantly smaller. These results indicate that the presence of asthma in successive generations is more likely caused by shared genes than shared environmental risk factors; however, substantial heterogeneity among families may exist. Genetic analysis, especially among the families with an obvious familial component in development of asthma, may enhance the chances of revealing the pathogenetic mechanisms

Adolescent↗

PubMed1998

Serum lipids, lipoproteins, and lipid metabolizing enzymes in identical twins discordant for obesity.

Obesity is associated with adverse changes in plasma lipoprotein metabolism, but it is not known completely how this association is modified by genetic factors. We assessed the contribution of obesity to serum lipid and lipoprotein levels and lipid metabolizing enzyme activities by examining 23 identical twin pairs (9 male, 14 female) who had, on the average, an 18-kg intrapair difference in BW. Compared with lean co-twins, obese co-twins had approximately 20% higher low-density lipoprotein (LDL) cholesterol (P < 0.01), 20% lower high-density lipoprotein2 cholesterol (P = 0.010), and 90% (men) or 35% (women) higher (P < or = 0.06) total, very-low-density lipoprotein and LDL triglycerides. The pairs were divided into subgroups by the gender-specific median value of abdominal visceral fat (AVF) area in the obese co-twin and by apolipoprotein E 4 phenotype. The intrapair differences in serum cholesterol fractions were similar in twin pairs with high or low AVF, whereas only high AVF pairs showed significant differences in triglyceride fractions. The greatest intrapair differences in total, very-low-density lipoprotein and LDL triglycerides were observed in apolipoprotein E 4-positive pairs expressing high AVF. Compared with lean co-twins, lecithin cholesterol acyltransferase activity was 18% higher (P < 0.001) and hepatic lipase activity was 38% higher (P = 0.016) in obese co-twins with high AVF. When genetic factors are identical, obesity is associated with an atherogenic lipid profile, especially in subjects with high visceral fat accumulation.

Apolipoprotein E4↗