Genetic influences on cervical and lumbar disc degeneration: a magnetic resonance imaging study in twins.
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OBJECTIVE: Degenerative intervertebral disc disease is common; however, the importance of genetic factors is unknown. This study sought to determine the extent of genetic influences on disc degeneration by classic twin study methods using magnetic resonance imaging (MRI). METHODS: We compared MRI features of degenerative disc disease in the cervical and lumbar spine of 172 monozygotic and 154 dizygotic twins (mean age 51.7 and 54.4, respectively) who were unselected for back pain or disc disease. An overall score for disc degeneration was calculated as the sum of the grades for disc height, bulge, osteophytosis, and signal intensity at each level. A "severe disease" score (excluding minor grades) and an "extent of disease" score (number of levels affected) were also calculated. RESULTS: For the overall score, heritability was 74% (95% confidence interval [95% CI] 64-81%) at the lumbar spine and 73% (95% CI 64-80%) at the cervical spine. For "severe disease," heritability was 64% and 79% at the lumbar and cervical spine, respectively, and for "extent of disease," heritability was 63% and 63%, respectively. These results were adjusted for age, weight, height, smoking, occupational manual work, and exercise. Examination of individual features revealed that disc height and bulge were highly heritable at both sites, and osteophytes were heritable in the lumbar spine. CONCLUSION: These results suggest an important genetic influence on variation in intervertebral disc degeneration. However, variation in disc signal is largely influenced by environmental factors shared by twins. The use of MRI scans to determine the phenotype in family and population studies should allow a better understanding of disease mechanisms and the identification of the genes involved. (+info)
Marmoset species variation in the humoral antibody response: in vivo and in vitro studies.
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A comparison of the in vivo and in vitro antibody response capabilities of two marmoset species, Saguinus fuscicollis and Saguinus oedipus oedipus, revealed the former to be superior in elaborating humoral antibody. In vivo challenges with Escherichia coli lipopolysaccharide (LPS) and Salmonella typhi flagella consistently yielded higher antibody titres in S. fuscicollis; indeed, with LPS antigen, multiple inoculations of S.o. oedipus marmosets led ultimately to a decrease in antibody formation, in contrast to the anamnestic response of S. fuscicollis. This species differential in immune competence was also suggested in the in vitro stimulation of peripheral blood leucocytes (PBL) and spleen cells with sheep red blood cells (RBC). None of 55 S.o. oedipus PBL cultures and 49 of 89 (55%) S. fuscicollis cultures responded to the test antigen. A similar differential in response to sheep RBC was noted with the spleen cells of each species, although this report contrasts the antibody-forming potential of two marmoset species, a comparison of the immunological response profile of marmosets to those of other laboratory animals challenged with similar antigens suggests these primates may be relatively incompetent. The possible relationship between the haemopoietic chimerism of marmosets and a diminished immune competence is discussed. (+info)
Genetic determination of islet cell autoimmunity in monozygotic twin, dizygotic twin, and non-twin siblings of patients with type 1 diabetes: prospective twin study.
(3/905)
OBJECTIVE: To test the hypothesis that non-diabetic dizygotic and monozygotic twin siblings of patients with type 1 diabetes have a similar high prevalence of islet cell autoantibodies, thus suggesting that islet cell autoimmunity is mainly environmentally determined. DESIGN: Prospective twin study. SETTING: Two specialist centres for diabetes in the United States. PARTICIPANTS: Non-diabetic monozygotic twin (n=53), dizygotic twin (n=30), and non-twin (n=149) siblings of patients with type 1 diabetes; 101 controls. MAIN OUTCOME MEASURES: Analysis of progression to diabetes and expression of anti-islet autoantibodies. RESULTS: Monozygotic twin siblings had a higher risk of progression to diabetes (12/53) than dizygotic twin siblings (0/30; P<0.005). At the last follow up 22 (41.5%) monozygotic twin siblings expressed autoantibodies compared with 6 (20%) dizygotic twin siblings (P<0.05), 16 (10.7%) non-twin siblings (P<0.0001), and 6 (5.9%) controls (P<0.0001). Monozygotic twin siblings expressed multiple (>/=2) antibodies more often than dizygotic twin siblings (10/38 v 1/23; P<0.05). By life table analysis the probability of developing positive autoantibodies was higher among the monozygotic twin siblings bearing the diabetes associated HLA DQ8/DQ2 genotype than in those without this genotype (64.2% (95% confidence interval 32.5% to 96%) v 23.5% (7% to 40%) at 10 years of discordance; P<0.05). CONCLUSION: Monozygotic and dizygotic twins differ in progression to diabetes and expression of islet cell autoantibodies. Dizygotic twin siblings are similar to non-twin siblings. These two observations suggest that genetic factors play an important part in determination of islet cell autoimmunity, thus rejecting the hypothesis. In addition, there is a high penetrance of islet cell autoimmunity in DQ8/DQ2 monozygotic twin siblings. (+info)
Breast cancer risk in monozygotic and dizygotic female twins: a 20-year population-based cohort study in Finland from 1976 to 1995.
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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. (+info)
Genetic effects on weight change and food intake in Swedish adult twins.
(5/905)
BACKGROUND: Obesity is influenced by genetic and environmental factors. Additionally, synergistic effects of genes and environments may be important in the development of obesity. OBJECTIVE: The aim of this study was to test for genetic effects on food consumption frequency, food preferences, and their interaction with subsequent weight gain. DESIGN: Complete data on the frequencies of consumption of 11 foods typical of the Swedish diet were available for 98 monozygotic and 176 dizygotic twin pairs aged 25-59 y who are part of the Swedish Twin Registry. The data were collected in 1973 as part of a questionnaire study. Body mass index was measured in 1973 and again in 1984. RESULTS: There was some evidence that genetic effects influenced the frequency of intake of some foods. Similarity among monozygotic twins exceeded that among dizygotic twins for intake of flour and grain products and fruit in men and women, intake of milk in men, and intake of vegetables and rice in women, suggesting that genes influence preferences for these foods. Analyses conducted for twins reared together and apart also suggested greater monozygotic than dizygotic correlations, but cross-twin, cross-trait correlations were all insignificant, suggesting that the genes that affect consumption frequencies are not responsible for mediating the relation between the frequency of intake and weight change. CONCLUSIONS: Genetic effects and the frequency of intake are independently related to change in body mass index. However, there was no suggestion of differential genetic effects on weight gain that were dependent on the consumption frequency of the foods studied. (+info)
Fetal and infant death in mono- and dizygotic twins in England and Wales 1982-91.
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AIM: To quantify the level of risk for stillbirth and infant death in singleton compared with twin pregnancies, using national data; to determine the independent effects of zygosity, sex, and birthweight on these risks in twin pregnancies. METHODS: A retrospective national study was carried out of all singleton and twin birth and death registrations in England and Wales 1982-91, according to sex and birthweight group. Weinberg's rule was applied to the twin pairs to differentiate mono- from dizygotic twins. Relative risks for mono- compared with dizygous twins for both twins being stillbirths and for one of the pair being a stillbirth were determined. For twins where one was stillborn and the other live born, the relative risk of neonatal and infant mortality in the surviving co-twin was determined. RESULTS: There were 6 563 834 registered singletons and 70772 registered twin pairs for the period under study. Monozygotic twins had a relative risk of: 18.91 (95% CI 12.48-28.64) for both twins being stillborn; 1.63 (95% CI 1.48-1.79) for one twin being a stillbirth; and 2.26 (95% CI 1.45-3.52) for the live born co-twin dying as a neonate. When both twins were live born and among singletons, the odds ratio for neonatal mortality of being male was 1.41 (95% CI 1.37-1.45) and there was a highly significant negative association with birthweight. After adjusting for birthweight group and sex, twins had a reduced neonatal mortality compared with singletons: odds ratio 0.91 (95% CI 0.85-0.96). CONCLUSIONS: Fetal death in one of monozygotic twins has serious implications for survival of the co-twin. Monochorionicity is probably the essential feature of the increased risk to the co-twin. It is imperative that all fetal deaths in multiple pregnancies are recorded and chorionicity determined if parents are to be adequately counselled. (+info)
QT interval is linked to 2 long-QT syndrome loci in normal subjects.
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BACKGROUND: The rate-corrected QT interval (QTc) is heritable, and the discovery of quantitative trait loci that influence the QTc would be an important step in identifying the genes responsible for life-threatening arrhythmias in the general population. We studied 66 pairs of unselected normal dizygotic (DZ) twin subjects and their parents in a sib-pair analysis. We tested for linkage of gene loci harboring genes known to cause the long-QT syndrome (LQT) to the quantitative trait QTc. METHODS AND RESULTS: We found genetic variance on QRS duration, QRS axis, T-wave axis, and QTc. Women had a longer QTc than men. Microsatellite markers were tested in the vicinity of the gene loci for the 5 known LQT genes. We found significant linkage of QTc with the loci for LQT1 on chromosome 11 and LQT4 on chromosome 4 but not to LQT2, LQT3, or LQT5. We also found linkage of the QRS axis with LQT2 and LQT3. CONCLUSIONS: We suggest that these quantitative trait loci may represent the presence of variations in LQT genes that could be important to the risk for rhythm disturbances in the general population. (+info)
Does zygosity influence the metabolic profile of twins? A population based cross sectional study.
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OBJECTIVE: To study the influence of zygosity on the metabolic variables involved in the pathophysiology of type 2 diabetes. DESIGN: Population based cross sectional study. SETTING: Odense University Hospital, Denmark. PARTICIPANTS: 125 monozygotic twin pairs and 178 dizygotic twin pairs of the same sex born between 1921 and 1940. MAIN OUTCOME MEASURES: Clinical characteristics of monozygotic and dizygotic twins with or without a family history of type 2 diabetes. RESULTS: Absolute prevalences of type 2 diabetes and impaired glucose tolerance according to the World Health Organisation criteria were similar in both the monozygotic and the dizygotic twins as were measurements of height, weight, body mass index, waist to hip ratio, and fasting plasma glucose and insulin concentrations. During the oral glucose tolerance test, monozygotic twins had a higher incremental plasma insulin area under the curve than dizygotic twins (10.05 (SD 0.68) v 9.89 (0.72) pmol/lxminutes, P<0.01) indicating insulin resistance. In twins with normal glucose tolerance and without first degree relatives or co-twins with type 2 diabetes or impaired glucose tolerance, both the glucose and insulin areas under the curve were higher among monozygotic twins (glucose 214.4 (88.3) v 189.8 (78.4) mmol/lxminutes, P<0.05; insulin 20 040 (14 865-32 554) v 17 625 (12 330-23 640) pmol/lxminutes, P=0.08). CONCLUSION: Zygosity influences both plasma glucose and plasma insulin concentrations during an oral glucose tolerance test. This supports an intrauterine influence on glucose homeostasis and perhaps on insulin resistance in humans. (+info)