Bernard Jeune

Estimation of apolipoprotein E genotype-specific relative mortality risks from the distribution of genotypes in centenarians and middle-aged men: apolipoprotein E gene is a "frailty gene," not a "longevity gene"

We developed a method to estimate genotype‐specific average relative mortality risk, R, from genotype distributions in cross‐sectional studies of people belonging to different age‐groups, and applied the method to new data from a study of apolipoprotein E genotypes (apoE) in 177 Danish centenarians and data from a study of 40‐year‐old Danish men. Twenty‐one percent of the centenarians were ϵ2‐carriers (genotypes ϵ2ϵ2 and ϵ3ϵ2) and 15% were ϵ4‐carriers (genotypes ϵ4ϵ4 and ϵ4ϵ3) compared to 13 and 29%, respectively, of the young men. The R‐values were 0.95 (95% CI 0.88 to 1.02) for ϵ2‐carriers and 1.13 (95% CI 1.05 to 1.22) for ϵ4‐carriers, using ϵ3ϵ3‐ and ϵ4ϵ2 genotypes as reference. Corresponding values for ϵ4‐carriers were obtained by using published data from a French and a Finnish study of centenarians, whereas the values for ϵ2‐carriers were about 0.90 with these data. The method to estimate mortality risk and the results associate with the view that the apoE gene is a “frailty gene.” On the other hand, if odds ratios are used to summarize data from studies of this kind, they are more impressive and may propagate the misconception that apoE is a “longevity gene”. Genet. Epidemiol. 19:202–210, 2000.

A tooth per child

same social status but who had different numbers of children and who fell into different dental categories. In 28 of these pairs, the twin with more children had fewer teeth (p<0·001). No such relationship was found for male twin pairs. In historic and prehistoric populations, caries and loss of teeth increased the risk of death. The long-term costs of childbearing on women’s health may have been substantial and they may still be significant.

Apolipoprotein E genotypes: Relationship to cognitive functioning, cognitive decline, and survival in nonagenarians

OBJECTIVES: To evaluate the extent to which relationships between apolipoprotein E, cognitive functioning, and survival in people aged 60 to 80 persist into advanced old age.

Genotypes for the cytochrome P450 enzymes CYP2D6 and CYP2C19 in human longevitY. Role of CYP2D6 and CYP2C19 in longevity.

AbstractObjective: To test whether some genotypes for CYP2D6 or CYP2C19 could contribute to longevity, we genotyped 241 Danish nonagenarians and centenarians for CYP2D6 and CYP2C19.nn Methods: For CYP2D6 we identified the alleles CYP2D6*1, CYP2D6*3 and CYP2D6*4 with allele-specific polymerase chain reaction (PCR). The CYP2D6*5 alleles were identified with a long PCR method. For CYP2C19 we identified the alleles CYP2C19*1, CYP2C19*2 and CYP2C19*3 with an oligonucleotide ligation assay. nn Results: The four alleles for CYP2D6 did not occur in Hardy-Weinberg proportions. The frequency of poor metabolism was slightly higher (10.2%) than expected [7.7%; odds ratio (OR) = 1.36 (0.75–2.40)]. The genotypes for CYP2C19 occur in Hardy-Weinberg proportions. The frequency of poor metabolism (3.8%) was not significantly different from a young control group [3.1%; OR = 1.21 (0.26–5.75)]. nn Conclusion: CYP2D6 could play a role in human longevity due to the lack of Hardy-Weinberg proportions. If CYP2D6 only plays a role in longevity by protecting the poor metabolizers from cancer, we should expect a rise in the frequency in these genotypes in Denmark from 7.7% among young adults to 10–11% among very old people. We found a frequency of poor metabolism of 10.2% in the very old group. CYP2C19 is – due to the occurrence of Hardy-Weinberg proportions and the expected number of poor metabolizers – unlikely to contribute to human longevity.

Thyroid Function, Morphology and Prevalence of Thyroid Disease in a Population‐Based Study of Danish Centenarians

OBJECTIVES: To investigate thyroid function, morphology, and autoimmunity in relation to physical function in an unselected population of centenarians.

Aspects of comfort and safety of condom A study of two thousand intercourses among volunteer couples

Aspects of comfort and safety of comdom. A study of two thousand intercourses among volunteer couples. Boldsen J. L., Jeune B. and Madsen P. C. Institute of Community Health, University of Odense, J. B. Winsløws Vej 17, DK-5000 Odense C, Denmark. In nearly 2000 intercourses 14 different types of condoms were tested by 80 heterosexual and seven homosexual volunteer couples. The test couples were generally quite experienced in the use off condoms. It appears that the condoms rarely (1.3%) ruptured or slipped of during the actural intercourse. This means that emphasis must be put on consistency and skill in the use of condoms rather on technical improvements in the promotion of condoms as a means of preventing the spread of sexually transmitted infections like HIV. Lubricated condoms and condoms that were not too small were preferred by both users and their partners. Other condom properties were significant but of minor concern for the participants of the study.

Survival experience of semi-skilled disability pensioners in Denmark

The purpose of this study was to estimate the survival prognosis of semi-skilled disability pensioners. The survival experience of 1353 invalid male members of the Danish Semiskilled Workers Union (SID) awarded disability pensions in 1975 was compared with a control group of members of the same union, matched geographically and by age. The two groups were followed until Nov. 30, 1978. For the follow-up period as a whole, the mortality risk among disability pensioners was estimated to be 6.8 times as high as that of controls. The relative risk of mortality was higher at the periods inception than at the end. A very high mortality level was found among disability pensioners awarded the highest level of disability pension, but no differences in mortality were found between disability pensioners awarded the lower levels of disability pension and the corresponding control group. The significance of medical and social factors in reducing the ability to work is discussed, as it relates to grounds for the awarding of disability pensions. The prognosis of one category of disability pensioners is very poor, while the survival prognosis of another is not significantly worsened, despite a considerable deterioration in the ability to work.

Biology and Genetics of Human Longetivity

Abstract. Human longevity is a multifactorial trait, which includes a network of genes combined with strong environmental factors. Biological and clinical characteristics of human beings are the result of the interaction between genes and the environment. Until about 1950 centenarians were quite rare in low‐mortality countries. Since then the number has more than doubled every 10 years and even the number of 105+ year old people is now increasing. This proliferation of centenarians is mainly a result of the decrease in oldest‐old mortality and probably due to changes of lifestyle and health care. Although studies of Danish twin pairs seem to indicate that genetic influence on human lifespan is only moderate, several gene loci contribute to longevity. Data are evident from the Italian Centenarian Study for apoproteinB, tyrosine hydroxylase and mitochondrial DNA loci among others studied (superoxide dismutases, ie. SOD1 and SOD2, poly(ADP‐ribose)polymerase and thyroid peroxidase). The data from the Danish Centenarian Study confirm the findings from the studies of French and Finnish centenarians on apolipoprotein E genotype with a higher frequency of epsilon‐2 and lower frequency of epsilon‐4. However, the apoE genotype seems not to be a key determinant of exceptional longevity: in 105+ year olds the epsilon‐4 allele was found in 4 out of 19 persons. Italian centanarians have a paradoxically marked hypercoagulability as demonstrated also by genetic markers. Also the von Willebrand factor was increased independently of the blood group. Studies on such atherosclerosis risk factors as lipoprotein(a) and homocysteine revealed that these two parameters may be high in Italian centenarians, but their genetic control possibly attenuates with age, and environmental factors may play a major role in the oldest‐old persons. Also interaction among genes is possible. All these studies suggest that longevity is a phoenomenon depending on multiple genetic and environmental factors. Further studies are needed for a better understanding of the complex interactions which allow people to reach a very old age.

Age of partners at first intercourse among Danish males and females

In 1984–1985 a representative sample of 286 Danish women (response rate = 75.3%) and 336 Danish men (response rate = 77.8%), ages 16–20 years, was interviewed about their first sexual intercourse. A cumulative frequency function was constructed and the median age at sexual debut was estimated at 16.8 years for both male and female. Generally the age difference between the partners at first intercourse was only a few years. However, the young women almost never reported their first sexual partner as younger than themselves. A cross-check was made of the information given by two homogeneous subsamples of the 47 young women and 80 young men who had their first sexual intercourse with a partner who was also a debutant. Self-reported age among the males differed significantly from the age of the first sexual partner as stated by the females in these subsamples. Therefore, there is bias in the reporting of age of partner at first intercourse. As the self-reported age at first sexual intercourse by young women agrees with the age of first partner as stated by young men, the bias seems to manifest itself predominantly as a systematic misreporting in the age of male partners of debutant females.

Prevalence of Smoking and Oral Contraception in a Sample of Danish Young Women

A representative sample of 286 Danish females aged 16-20 years were interviewed during the period April 1984 - February 1985. The response rate was 75%. Both use of oral contraception (OC) and smoking were common; 46.6% used OC, 34.2% smoked and 19.6% combined smoking and OC. The prevalence of smoking was significantly higher (42.0%) among OC-users than among nonusers (27.2%). The combination of smoking and OC was especially prevalent among young women with sexual debut before 16 years (36.8%). The association between smoking and the use of OC was significant both when tested unstratified (p < 0.05) and stratified by age at sexual debut (p < 0.01). Smoking was also associated with early debut of intercourse (p < 0.001). It has been reported that the combination of these two factors in adult women increase the risk for cardiovascular mortality. However, the health consequences later in life of combining smoking and OC at young ages have not been illuminated in the literature. These findings indicate the necessity for prospective studies of young women.