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Biomedical subjects

Kaare Christensen

Publications and source records attributed to Kaare Christensen.

At least 73 records · Page 4Linked to original sources
PubMed2004

Genetic influence on inflammation variables in the elderly.

BACKGROUND: Inflammation variables (C-reactive protein [CRP], fibrinogen, and soluble intercellular adhesion molecule-1 [sICAM-1]) have been identified as risk factors for cardiovascular disease. It is still not known how much the regulation of inflammatory risk factors is determined by genetic factors, and the aim of this study was to determine the heritability of these inflammation variables and of the acute phase regulating cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) at older ages. METHODS AND RESULTS: The heritability of CRP, fibrinogen, sICAM-1, IL-6, and TNF-alpha was determined in a twin study consisting of 129 monozygotic twin pairs and 153 dizygotic same-sex twins aged 73 to 94 years who participated in the Longitudinal Study of Aging of Danish Twins. Furthermore, we determined the influence of selected genetic polymorphisms on the plasma level variations. Genetic factors accounted for 20% to 55% of the variation in plasma levels of the inflammation variables. The highest heritability was found for sICAM-1. The genetic polymorphisms we studied explained only a small, insignificant part of the heritability. CONCLUSIONS: This study in elderly twins provides evidence for a substantial genetic component of inflammatory cardiovascular risk factors among the elderly.

Acute-Phase Proteins↗
PubMed2004

Interferon regulatory factor 6 (IRF6) gene variants and the risk of isolated cleft lip or palate.

BACKGROUND: Cleft lip or palate (or the two in combination) is a common birth defect that results from a mixture of genetic and environmental factors. We searched for a specific genetic factor contributing to this complex trait by examining large numbers of affected patients and families and evaluating a specific candidate gene. METHODS: We identified the gene that encodes interferon regulatory factor 6 (IRF6) as a candidate gene on the basis of its involvement in an autosomal dominant form of cleft lip and palate, Van der Woude's syndrome. A single-nucleotide polymorphism in this gene results in either a valine or an isoleucine at amino acid position 274 (V274I). We carried out transmission-disequilibrium testing for V274I in 8003 individual subjects in 1968 families derived from 10 populations with ancestry in Asia, Europe, and South America, haplotype and linkage analyses, and case-control analyses, and determined the risk of cleft lip or palate that is associated with genetic variation in IRF6. RESULTS: Strong evidence of overtransmission of the valine (V) allele was found in the entire population data set (P<10(-9)); moreover, the results for some individual populations from South America and Asia were highly significant. Variation at IRF6 was responsible for 12 percent of the genetic contribution to cleft lip or palate and tripled the risk of recurrence in families that had already had one affected child. CONCLUSIONS: DNA-sequence variants associated with IRF6 are major contributors to cleft lip, with or without cleft palate. The contribution of variants in single genes to cleft lip or palate is an important consideration in genetic counseling.

Cleft Lip↗
PubMed2004

Fecundity and twinning. A study within the Danish National Birth Cohort.

BACKGROUND: Decreased fecundity has been hypothesized as one of the causes of the widespread decline in twin rates in the 1960s and 1970s. The association between high fecundity and twinning is not, however, well documented. METHODS: In the Danish National Birth Cohort, we identified 56 295 births (including 729 twin deliveries) with data on pregnancy planning and time to pregnancy (TTP) and no report of infertility treatment. We estimated the odds ratio (OR) of twinning as a function of TTP and having planned a pregnancy. RESULTS: Increasing TTP correlated with decreased twinning rates. Compared with women who conceived within 2 months of trying, women who took longer than 1 year had an OR of 0.55 (95% confidence interval 0.39-0.77) of giving birth to twins. The association was slightly stronger for opposite sex twins. Women not planning a pregnancy had a lower rate of opposite sex twins than planners, but a comparable rate of same sex twins. We saw an excess of same sex pairs in women conceiving despite contraception. CONCLUSIONS: A long TTP is associated with a reduced risk of twinning. The marked decline observed in the 1960s and 1970s may derive from a widespread decrease in fecundity.

Adult↗
PubMed2004

Long term follow up study of survival associated with cleft lip and palate at birth.

OBJECTIVE: To assess the overall and cause specific mortality of people from birth to 55 years with cleft lip and palate. DESIGN: Long term follow up study. SETTING: Danish register of deaths. PARTICIPANTS: People born with cleft lip and palate between 1943 and 1987, followed to 1998. MAIN OUTCOME MEASURES: Observed and expected numbers of deaths, summarised as overall and cause specific standardised mortality ratios. RESULTS: 5331 people with cleft lip and palate were followed for 170 421 person years. The expected number of deaths was 259, but 402 occurred, corresponding to a standardised mortality ratio of 1.4 (95% confidence interval 1.3 to 1.6) for males and 1.8 (1.5 to 2.1) for females. The increased risk of mortality was nearly constant for the three intervals at follow up: first year of life, 1-17 years, and 18-55 years. The participants had an increased risk of all major causes of death. CONCLUSIONS: People with cleft lip and palate have increased mortality up to age 55. Children born with cleft lip and palate and possibly other congenital malformations may benefit from specific preventive health measures into and throughout adulthood.

Adolescent↗
PubMed2004

Genetic and environmental contributions to back pain in old age: a study of 2,108 danish twins aged 70 and older.

STUDY DESIGN: Self-reported 1-month prevalence of back pain in older twins assessed at intake in a population-based longitudinal survey. OBJECTIVES: To determine the relative contribution of genetic and environmental factors to back pain in old age. SUMMARY OF BACKGROUND DATA: To date, genetic contributions to back pain in old age have not been assessed, to the authors' best knowledge. METHODS: Interview data given at entry into a nationwide cohort-sequential population-based survey of Danish twins aged 70 years and older in 1995, 1997, 1999, and 2001 form the basis of this analysis. Analysis of twin similarity was estimated using probandwise concordance rates, odds ratios, and tetrachoric correlations for back pain. Heritability (proportion of the population variance attributable to genetic variation) was estimated by bivariate probit estimation and adjusted for known significant environmental factors. Odds ratios for known environmental effects were estimated after controlling for age, sex, and genetic effects. RESULTS: Modest and nonsignificant differences between monozygotic and dizygotic twin pairs were found for probandwise concordance rates, odds ratios, and tet-rachoric correlations for both men and women. In the bivariate probit estimation, a current or previous diagnosis of osteoporosis, degenerative joint disease, or lumbar disc prolapse was found to significantly affect the risk of back pain. Additive genetic effects explained approximately one fourth of the liability to report back pain in men and none of the occurrence in women. Individual environmental effects were found to explain roughly 75% of the occurrence of back pain in men and 100% in women. CONCLUSIONS: Additive genetic effects are modest contributors to back pain in older men but not in women. A current or previous medical diagnosis of osteoporosis, degenerative joint disease, or lumbar disc prolapse is-strongly associated with back pain, also when genetic factors are controlled for. Because of inherent methodologic issues, this estimate of the genetic influence on back pain in old age is probably conservative.

Age Distribution↗
PubMed2004

Back and neck pain exhibit many common features in old age: a population-based study of 4,486 Danish twins 70-102 years of age.

STUDY DESIGN: Cross-sectional and longitudinal analysis of data comprising 4486 Danish twins 70-102 years of age. OBJECTIVES: To describe the 1-month prevalence of back pain, neck pain, and concurrent back and neck pain and the development of these over time, associations with other health problems, education, smoking, and physical, and mental functioning. SUMMARY OF BACKGROUND DATA: Back pain and neck pain are prevalent symptoms in the population; however, there is little research addressing these conditions in older age groups. METHODS: Extensive interview data on health, lifestyle, social, and educational factors were collected in a nationwide cohort-sequential study of 70+-year-old Danish twins. Data for back pain, neck pain, lifetime prevalence of a comprehensive list of diseases, education, and self-rated health were based on self-report. Physical and mental functioning were measured using validated performance tests. Data including associated factors were analyzed in a cross-sectional analysis for answers given at entry into the study, and longitudinal analysis was performed for participants in all four surveys. RESULTS: The overall 1-month prevalence for back pain only was 15%, for neck pain only 11%, and for concurrent back and neck pain 11%. The prevalence varied negligibly over time and between the age groups, and 63% of participants in all surveys had no episodes or only one episode of back or neck pain. Back pain and neck pain were associated with a number of other diseases and with poorer self-rated health. Back and neck pain sufferers had significantly lower scores on physical but not cognitive functioning. CONCLUSIONS: Back pain and neck pain are common, intermittent symptoms in old age. Back pain and neck pain are associated with general poor physical health in old age.

Aged↗
PubMed2004

Evidence for an association of methylene tetrahydrofolate reductase polymorphism C677T and an increased risk of fractures: results from a population-based Danish twin study.

Osteoporotic fractures are some of the major causes of morbidity and health care expenditure among the elderly. Identifying subjects at risk could be of major importance since several preventive treatments are now available. A large genetic component in the development of osteoporosis has been established. Previous studies concerning association of the common point mutation C677T in methylentetrahydrofolate reductase (MTHFR) and osteoporosis have revealed contradictory results. The aim of this study was to test the association between the MTHFR polymorphism, homocysteine, and fractures in a population-based sample of Danish twins aged 73+. In total, 689 subjects, with a mean age of 78 years, participated. Genotype and data of fractures are available from 687 subjects--144 with a previously diagnosed fracture. The genotype distribution is as follows: CC, CT, and TT genotypes, 317 (46.1%), 298 (43.3%), and 73 (10.6%), respectively. Using the proportional odds-ratio model adjusted for age, gender, and body mass Index, the odds-ratio of fracture was 1.5 per number of T alleles--meaning that fracture risk is 1.5 times higher in the CT group compared with the CC group and again 1.5 times higher in the TT group compared with the CT group. Homocysteine, smoking, and self-reported hormone use provided no significant contribution to fracture risk. Using biometrical modelling, the heritability of the liability to fractures was found to be approximately 0.10, when the effect of the MTHFR locus was included, and 0.07 when it was omitted. But both confidence intervals include zero and the estimates are therefore not significant. In conclusion, we here provide evidence for a significant impact of the MTHFR genotype on the occurrence of fractures in an elderly Danish population.

Aged↗
PubMed2004

Application of kinetic polymerase chain reaction and molecular beacon assays to pooled analyses and high-throughput genotyping for candidate genes.

BACKGROUND: The addition of DNA analysis to epidemiologic studies that have traditionally incorporated demographic and interview data can provide additional power and open new avenues for investigation. DNA can be obtained from a variety of tissues, but each has attendant variation in sample quantity, quality, and cost of acquisition. Analytic approaches for DNA genotyping are under constant development, but current applications allow small amounts (less than 2 ng per assay) of DNA to be used for genotyping. METHODS: In this report, we designed effective assays for a spectrum of genes using either kinetic polymerase chain reaction (PCR) or molecular beacon applications. We also investigated the extent to which DNA use and reagent cost could be minimized. Kinetic PCR assays were also applied to investigate the potential of pooled sample analysis. RESULTS: Our results show that small amounts of DNA can be successfully amplified in a high-throughput fashion using both kinetic PCR and molecular beacon methods. Greater than 97% of the genotype results from these two methods are consistent. In addition, error rates in allele frequency measurements using DNA pools of 100 or more samples were often less than 1% and usually less than 3%, which provides another option for substantially minimizing the costs of genotyping in studies involving large numbers of individuals. CONCLUSIONS: Effective assays have been designed for a spectrum of genes widely studied in birth defects, including: MTHFR, NAT1, TGFA, RFC1, PAX9, EPHX1, and SKI. An efficient assay has been designed for the detection of the presence of X and Y chromosomes, which can be applied to the studies of sex chromosome abnormalities or sample quality control.

Carrier Proteins↗
PubMed2004

Genetic influence on prolonged gestation: a population-based Danish twin study.

OBJECTIVE: The purpose of this study was to test a possible genetic component to prolonged gestation. STUDY DESIGN: The gestational duration of single, first pregnancies by both female and male twins was obtained by linking the Danish Twin Registry, The Danish Civil Registration System, and the Danish Medical Birth Register. A total of 2588 same-sex twin pairs of whom both cotwins became parents during 1978 to 1996 were identified. RESULTS: The concordance rate for female twin pairs for a gestation of > or =41 weeks and > or =42 weeks was higher for monozygotic twin pairs than for dizygotic twin pairs, which indicates genetic effects. Biometric modeling suggested that genetic factors account for 23% to 30% of the liability to prolonged gestation. The difference in concordance rate between monozygotic and dizygotic male twin pairs was small, and the best fitting model indicated no genetic factors. CONCLUSION: Maternal genes influence prolonged gestation. However, a substantial paternal genetic influence through the fetus was not found.

Denmark↗
PubMed2004

Heritability of biochemical kidney markers and relation to survival in the elderly--results from a Danish population-based twin study.

BACKGROUND AND AIM: We performed a twin study to assess the relative contribution of genetic and environmental factors to serum levels of urea, creatinine, urate and sodium in a population of 688 elderly twins (73-95 years). Furthermore, we tested the association between these biochemical values and mortality to examine the consequence of an abnormal biochemical kidney parameter in an aging population. RESULTS: A third to a half of the variation in the biochemical kidney tests is due to genetic factors except for creatinine in males. Survival analysis show that all four parameters influence mortality and values below reference interval for urea and urate have a more pronounced impact on survival [hazard ratios (95% confidence interval): 2.32 (1.03-5.26) and 3.56 (1.46-8.69), respectively] than values above [1.20 (0.87-1.64) and 1.50 (1.11-2.02), respectively]. Increased creatinine (above 130 micromol/l) and decreased sodium (below 136 mmol/l) also have a significant impact on survival with hazard ratios on 1.83 (1.13-2.95) and 1.56 (1.22-1.99), respectively. Between 5% and 44% of the measured values are outside the established reference interval. CONCLUSION: This study provides evidence for the importance of genetic factors in determining the biochemical kidney parameters in an aging population. Furthermore, our data shows that abnormal kidney parameters are common in older adults and results in a significant increase in mortality risk.

Aged↗
PubMed2004

A polymorphic marker in the first intron of the Werner gene associates with cognitive function in aged Danish twins.

Werner's syndrome is a premature aging syndrome with many features common to normal aging. The possible association between phenotypic markers for normal aging and SNP's in the WRN gene was investigated in 426 dizygotic, Danish twins age 70-90 years. All participants were scored every second year using a number of physical and cognitive tests. In addition their self-rated health was registered as well as self reported status with regards to nine diseases. Blood was drawn from all participants and purified DNA was typed for four SNP's in the WRN gene. The four SNP's were located in intron 1, exon 6, exon 9 and exon 34. In an unpaired analysis of this material a significant association between the intron 1 SNP and cognitive function was demonstrated. Our finding, which will need corroboration in independent samples, therefore may suggest that the t-allele of the intron 1 SNP is beneficial to cognitive function. However, since the t-allele of this SNP is very rare, we did not encounter any tt-homozygous individuals for this allele.

Activities of Daily Living↗
PubMed2004

Association between low self-rated health and heterozygosity for -110A > C polymorphism in the promoter region of HSP70-1 in aged Danish twins.

We have studied the possible association between the -110A > C polymorphism in the promoter region of one of the heat shock protein genes HSP70-1 with human longevity in a cohort of aged Danish twins. This cohort includes individuals aged between 70 and 91 years (mean = 75.6 years), who are categorized according to the presence or absence of various diseases and according to the various, age-related parameters for which a genetic component has already been defined. Four hundred DNA samples from the cohort were genotyped using real-time PCR. Aging phenotypes (diseases, physical and cognitive functioning) were compared with regard to genotype. Of all the aging phenotypes studied, self-rated health and relative self-rated health, which represent an individual's overall sense of physical well-being and which have been shown to be both predictors of survival at older ages and better indicators of future survival than objectively measured health status, were associated with the polymorphism. An association was found between low self-rated health and heterozygosity for -110A > C polymorphism in the promoter region of HSP70-1 in aged Danish twins.

Aged↗
PubMed2004

Apolipoprotein E genotype frequency patterns in aged Danes as revealed by logistic regression models.

Although the ApoE gene has been intensively studied in aging research, most of the studies conducted so far have been based on the traditional case-control design with subjects consisting of young controls and long-lived cases. The genotype frequency pattern in and between the two age-groups has been rarely investigated due to limitations in either research design or data analytical method. In this study, we genotyped 748 individuals (including both twin pairs and unrelated individuals) aged from 73 to 95 with aim at examining the genotype frequency trajectory of ApoE gene at high ages. Binomial and multinomial logistic regression models have been applied to model the gene frequency as a function of age and to investigate the modes of gene function (dominant, recessive, additive). The generalized estimation equations (GEEs) are introduced to account for the intra-pair genotype correlation in the twin pairs included in the data. Both the observed and the fitted frequencies show a constantly declining pattern of ApoE epsilon4 allele as age advances indicating a significant and steadily deleterious effect of the dominant allele that increases the hazard of death at high ages.

Aged↗
PubMed2004

The catalase -262C/T promoter polymorphism and aging phenotypes.

A low level of the central antioxidant enzyme catalase has been suggested to be a risk factor for diseases influenced by oxidative stress. In this study, we investigated the possible association of the catalase -262C/T polymorphism with survival, physical and cognitive functioning, and a number of oxidative stress-mediated disorders. The study population was 2223 Danish individuals, aged 45-93 years, drawn from three population-based surveys. The results suggest that the catalase -262C/T polymorphism is not associated with either survival, or the majority of the age-related phenotypes investigated. However, our data indicate a statistical significant association of TT homozygosity with improved physical functioning as well as a trend of the T allele conferring an improved general cognitive functioning, although these results did not remain significant after correcting for multiple testing. The results raise the hypothesis that the catalase -262T allele serves as protection against neurodegenerative and physical decline, although replication in other studies is warranted for confirmation of these findings.

Aged↗
PubMed2004

Reproducibility and validity of simple questions to identify urinary incontinence in elderly women.

BACKGROUND: Epidemiologic studies are dependent on simple and valid questions to assess the prevalence and type of urinary incontinence. OBJECTIVE: To examine the reproducibility and validity of two standardized questions seeking to identify stress and urge incontinence among elderly women. METHODS: A random sample of 421 women 75 years or older living in the center of Odense, Denmark, were invited to participate, and 223 (53%) accepted a first interview in their home. A sample of 154 women were selected for a second interview with the same questions [accepted by 144 (94%)]. The second visit also included a long open interview about incontinence and was followed by a prospective registration of leakages. RESULTS: In the first interview 39% (95% confidence interval (CI) 34-47%) of the elderly women reported incontinence. The reliability of the questions was acceptable [kappa of 0.81 (95% CI 0.34-0.89)] with percent agreement of 90% (95% CI 84-95%) between first and second interviews for all incontinence (stress and/or urge). When the open interview was used as a "gold standard," the questions showed acceptable validity: a sensitivity of 0.91 (95% CI 0.86-0.96) and a specificity of 0.86 (95% CI 0.80-0.92) for all incontinence. CONCLUSION: Standardized questions about incontinence give reproducible answers and produce information that is comparable to a long open interview.

Aged↗
PubMed2004

Genetic and environmental influences on urinary incontinence: a Danish population-based twin study of middle-aged and elderly women.

BACKGROUND: Familial clustering has been reported for urinary incontinence (stress and urge), but different etiologies for the two types of incontinence have been suggested. OBJECTIVE: The aim of this study was to estimate the relative influence of genetic and environmental factors on stress, urge, and mixed incontinence among elderly and middle-aged women. METHODS: This is a population-based classical twin study of 1168 female twin pairs [548 monozygotic (MZ) and 620 dizygotic (DZ)] from a middle-aged (46-68 years) and an old (70-94 years) cohort identified in the Danish Twin Registry. Urinary incontinence was assessed with the help of two validated questions identifying stress and urge incontinence in interviews. RESULTS: For urge incontinence, the tetrachoric correlation was significantly higher for MZ twins, compared to that for DZ twin pairs in both middle-aged [0.51 (95% CI: 0.26-0.71) versus -0.22 (95% CI: -0.59-0.18)] and elderly [0.50 (95% CI: 0.27-0.68) versus 0.28 (95% CI: 0.02-0.42)], indicating genetic effects. The heritability of urge incontinence was 42% (95% CI: 16-63%) among middle-aged women and 49% (95% CI: 29-65%) among the elderly. Moreover, mixed incontinence had a substantial genetic component. The role of genetic factors was less clear in stress incontinence. CONCLUSIONS: Genetic factors play a substantial role in the development of urge and mixed incontinence, whereas the role of genetic factors in stress incontinence is less prominent.

Aged↗