Offspring Of Men Research Articles

Do the Transmissible Liability Index (TLI) and Adolescent Cannabis Use Predict Paranoid and Schizotypal Symptoms at Young Adulthood?

Background : Adolescent cannabis use is an established risk factor for the development of psychosis, but the premorbid vulnerability factors and specificity versus generality of the psychotic symptom domains affected in cannabis-psychosis relationships remain incompletely understood. To improve our understanding of these relationships, we used longitudinal data to examine the individual and interactive effects of preadolescent transmissible liability to substance use disorders (SUD), measured via the transmissible liability index (TLI), and adolescent cannabis use on the development of two distinct psychotic symptom domains, paranoid and schizotypal personality traits in young adulthood. Methods: We performed secondary analysis of data from the Center for Education and Drug Abuse (CEDAR) study, which longitudinally assessed offspring of men with (N = 211) and without (N = 237) lifetime history of SUD at ages 10-12, and across adolescence as they transitioned to young adulthood. TLI scores were calculated at age 10-12, self-reported cannabis use was assessed at age 16, and paranoid and schizotypal symptoms were assessed at age 19. Results: Cannabis use at age 16 and family history of SUD were significantly associated with paranoid and schizotypal symptoms at age 19, but TLI scores were not. The interactive effect of TLI x cannabis use was also not significant. Paranoid and schizotypal symptoms showed different dose-dependent sensitivities to cannabis exposure at age 16. Conclusions: These findings indicate that adolescent cannabis use and family history of SUD differentially contribute to the development of paranoid and schizotypal personality traits through mechanisms that do not include behavioral disinhibition.

Do paternal semen parameters influence the birth weight or BMI of the offspring? A study from the Utah Population Database.

To study the role of individual semen parameters on the offspring birth weight and body mass index (BMI) from a population of men evaluated in an assisted reproduction technology (ART) clinic compared to fertile controls. We performed a retrospective study using a cohort with fertile, age-matched controls of men evaluated with semen analysis at the University of Utah Andrology Clinic from 1996 to 2011 and Intermountain Healthcare from 2002 to 2011. We use the offspring from both our sub-fertile cohort and controls using the Utah Population Database. The two main outcomes of interest were offspring birth weight and adolescent BMI. The offspring of men with impaired sperm parameters had significantly lower birth weight compared to fertile control offspring. Low-concentration offspring weighed 158g less (95% CI - 278~- 38; p = 0.01), low total count weighed 172g less (95% CI - 294~- 51; p = 0.005), and low total motility weighed 155g less (95% CI - 241~- 69; p < 0.001) compared to those of the controls. When we controlled for the use of ART within the sub-fertile group, we found that there was a significant trend of increasing birth weight across levels of total motile count and total sperm count compared to the azoospermic group. We did not find any consistent significant differences between the subject and control adolescence BMI based on semen parameters. Despite limitations within our population-based dataset, we found that poor quality semen analysis parameters pointed towards an association with low birth weight in the offspring of sub-fertile men compared to the offspring of normal fertile controls. However, in contrast to studies of ART effects on offspring, we did not find evidence of long-term associations between semen quality and offspring BMI.

Birth rates among male cancer survivors and mortality rates among their offspring: a population-based study from Sweden

BackgroundWith improvements in treatment of cancer, more men of fertile age are survivors of cancer. This study evaluates trends in birth rates among male cancer survivors and mortality rates of their offspring.MethodsFrom the Swedish Multi-generation Register and Cancer Register, we identified 84,752 men ≤70 years with a history of cancer, for which we calculated relative birth rates as compared to the background population(Standardized Birth Ratios, SBRs). We also identified 126,696 offspring of men who had cancer, and compared their risks of death to the background population(Standardized Mortality Ratio, SMRs). Independent factors associated with reduced birth rates and mortality rates were estimated with Poisson modelling.ResultsMen with a history of cancer were 23 % less likely to father a child compared to the background population(SBR 0.77, 95 % Confidence Interval[CI] 0.75–0.79). Nulliparous men were significantly more likely to father a child after diagnosis (SBR 0.81, 95 % CI 0.79–0.83) compared to parous men (SBR 0.68, 95 % CI 0.66–0.74). Cancer site(prostate), onset of cancer during childhood or adolescence, parity status at diagnosis(parous), current age(>40 years) and a recent diagnosis were significant and independent predictors of a reduced probability of fathering a child after diagnosis.Of the 126,696 children born to men who have had a diagnosis of cancer, 2604(2.06 %) died during follow up. The overall mortality rate was similar to the background population(SMR of 1.00, 95 %CI 0.96–1.04) and was not affected by the timing of their birth in relation to father’s cancer diagnosis.ConclusionMale cancer survivors are less likely to father a child compared to the background population. This is influenced by cancer site, age of onset and parity status at diagnosis. However, their offspring are not at an increased risk of death.

OP0199 No Increased Risk of Congenital Malformations after Preconception Paternal Exposure to Dmards

BackgroundThe risk of congenital malformations in offspring of men with inflammatory joint diseases (IJD) treated with disease modifying antirheumatic drugs (DMARDs) before conception is largely unknown.ObjectivesTo study the occurrence of...

Risk of Birth Abnormalities in the Offspring of Men With a History of Cancer: A Cohort Study Using Danish and Swedish National Registries

BackgroundThe potential mutagenic effects of cancer therapies and the growing number of young male cancer survivors have given rise to concern about the health of their offspring.MethodsWe identified all singleton children born alive in Denmark between 1994 and 2004 and in Sweden between 1994 and 2005 (n = 1 777 765). Of the 8670 children with a paternal history of cancer, 8162 were conceived naturally and 508 were conceived using assisted reproductive technologies (ARTs) (in vitro fertilization or intracytoplasmatic sperm injection). Of the 1 769 0795 children without a paternal history of cancer, 25 926 were conceived using ARTs. Associations between paternal history of cancer and risk of adverse birth outcomes of children conceived naturally or by ARTs were investigated using log-linear binomial models, yielding risk ratios (RRs) with 95% confidence intervals (CIs). All statistical tests were two-sided.ResultsThe offspring of male cancer survivors were more likely to have major congenital abnormalities than the offspring of fathers with no history of cancer (RR = 1.17, 95% CI = 1.05 to 1.31, P = .0043, 3.7% vs 3.2%). However, the mode of conception (natural conception or ARTs) did not modify the association between paternal history of cancer and risk of congenital abnormalities (natural conception, RR = 1.17, 95% CI = 1.04 to 1.31; ARTs, RR = 1.22, 95% CI = 0.80 to 1.87, Pinteraction = .84).ConclusionWe observed a statistically significant but modest increase in the risk of major congenital abnormalities among offspring of males with a history of cancer, independent of the mode of conception.

Effect of Paternal Alcohol and Drug Dependence on Offspring Conduct Disorder: Gene—Environment Interplay

Not only are substance-use disorders and externalizing disorders frequently comorbid, they often co-occur in families across generations. The current study examined the role of genetic and environmental influences in the relationship between paternal histories of drug dependence or alcohol dependence and offspring conduct disorder using an offspring-of-twins design. Participants were male twins (n = 1,774) from the Vietnam Era Twin Registry, their offspring (n = 1,917), and mothers of the offspring (n = 1,202). Twins had a history of drug dependence, alcohol dependence, or neither. Based on the father's and his co-twin's drug-dependence or alcohol-dependence history and zygosity, risk groups were constructed to reflect different levels of genetic and environmental risk that were then used to predict offspring conduct disorder. After controlling for potentially confounding variables, the offspring of men with a history of drug dependence or alcohol dependence had significantly higher rates of conduct disorder, compared with offspring of men without this history. Offspring at higher genetic risk had higher rates of conduct disorder. High-risk offspring at lower environmental risk had lower rates of conduct disorder but only in the case of paternal drug-dependence risk. Lower environmental risk did not influence rates of offspring conduct disorder when the father had an alcohol-dependence history. Genetic risk associated with both paternal drug-dependence and paternal alcohol-dependence histories predicted offspring conduct-disorder risk, but only risk associated with paternal drug-dependence history was mitigated by having a low-risk environment. These results demonstrated a significant gene-environment interaction effect.

Paternal Age and Risk of Schizophrenia in Adult Offspring

Most past studies have affirmed a relationship between having an older father and the risk of a schizophrenic disorder; many, however, are limited methodologically. Older paternal age has been linked with several congenital disorders, ostensibly because of new autosomal dominant mutations in the male germ-cell line. For these reasons the investigators looked at data from the birth cohort of the Prenatal Determinants of Schizophrenia study to learn whether the risk of schizophrenia does increase with advancing paternal age. Unlike other studies, biological paternity was confirmed in a majority of cases. The cohort of 12,094 individuals, members of the Kaiser Foundation Health Plan after 1980, included 71 persons diagnosed as having schizophrenia or other disorders in the schizophrenia spectrum. The risk of these disorders increased as paternal age increased. Modeling paternal age as a continuous variable related to disease risk in adult offspring, a strong trend toward an association was evident. A significant association remained after adjusting for maternal age. The adjusted rate ratio associated with each 10-year increase in paternal age was 1.86, indicating a near doubling in the rate of adult schizophrenia-spectrum disorders in the offspring of men who were 10 years older at the child's birth. Adjusting for paternal race/ethnicity, paternal education, and parity did not appreciably alter the association. Limiting the outcome to schizophrenia proper, the rate ratio for each 10-year increase in paternal age, adjusting for maternal age, was 1.89. This prospective birth cohort study points to a significant and dose-dependent relationship between older paternal age and the risk that a child will have schizophrenia or a related disorder. Should the concept of de novo mutations be confirmed, it is conceivable that candidate genes for schizophrenia will be discovered.

Reproductive outcome according to semen quality in couples with infertility problems

Reproductive outcome according to semen quality in couples with infertility problems

Suicidality in Offspring of Men with Substance Use Disorder: Is There a Common Liability?

SUMMARY Suicide is the outcome of a discrete behavioral act which may precede or emerge consequent to a substance use disorder (SUD). A question that has yet to be empirically addressed pertains to the extent to which SUD and suicide have a common liability. The results reported herein indicate that psychological dysregulation in childhood is a risk factor for SUD but not suicidality. Offspring of men with SUD do, however, report a higher rate of suicidal ideation and attempts compared to offspring of psychiatrically normal men. These findings indicate that the risk for suicide and SUD do not completely map to each other but that there may be as yet unidentified factors which are associated with both outcomes.

Transmission of Neglect in Substance Abuse Families: The Role of Child Dysregulation and Parental SUD

SUMMARY Paternal and maternal models of transmission of child neglect were tested separately in 10–12 year old offspring of men with a substance use disorder (SUD) and psychiatrically normal men (n = 156). The model hypothesizes that childhood neglect experienced by parents is related to their neglectful parenting moderated by psychological dysregulation in the child and by parental SUD. The paternal model was not confirmed. However, it was found that a history of childhood neglect in the mother was related to seventy of neglect of her offspring. Child dysregulation was independently related to neglect severity and also enhanced the magnitude of association between history of neglect experienced by the mother and the severity of her neglectful parenting. In addition, SUD in the mother directly correlated with severity of neglectful parenting. Maternal SUD also moderated the association between her history of childhood neglect and severity of neglectful parenting. The ramifications of these results for understanding the etiology and impact of child neglect on the risk for SUD are discussed.

Unilateral renal agenesis associated with congenital bilateral absence of the vas deferens: phenotypic findings and genetic considerations

An association between congenital bilateral absence of the vas deferens (CBAVD), normal renal anatomy and cystic fibrosis (CF) gene mutations is well established (CF/CBAVD). We postulate that unilateral renal agenesis (URA) and CBAVD (URA/CBAVD) may have a non-CF mutation-mediated genetic basis that leads to abnormal development of the entire mesonephric duct at a very early stage in embryo development (< or =7 weeks). The physical, laboratory and radiographic findings of men with URA/CBAVD (n = 17) and CF/CBAVD (n = 97) were compared; the fertilization and pregnancy rates in the URA/CBAVD population calculated, and the incidence of renal agenesis in immediate family members and offspring of men with URA/CBAVD analysed. No statistical differences could be identified within any of the above comparisons. The fertilization rate for the URA/CBAVD group was 58.2 +/- 26.3%. Eight infants and two fetuses had normal renal anatomy, while one terminated male fetus had bilateral renal and vasal agenesis. Thirty first-order relatives had normal renal units. Anatomical expression of the reproductive ductal derivatives in men with URA/CBAVD and CF/CBAVD was similar, but the phenotypic outcome of the renal portion of the mesonephric duct was different. The potential for transmission of this fatal anomaly reinforces the need for prenatal ultrasounds with all pregnancies involving URA/CBAVD men.

Fetal death and congenital malformation in babies born to nuclear industry employees: report from the nuclear industry family study

There is some concern about the genetic effects of exposure to low-level ionising radiation, but the evidence is sparse and conflicting. Most work has concentrated on cancer in offspring and little has been done on adverse reproductive outcome. We aimed to assess whether the offspring of men and women who are occupationally exposed to ionising radiation are at increased risk of fetal death and congenital malformation. We analysed pregnancies reported by an occupational cohort of nuclear industry workers in the UK, employed at establishments operated by the Atomic Energy Authority, Atomic Weapons Establishment, and British Nuclear Fuels. Employment and radiation monitoring data supplied by employers was linked to each pregnancy. 11,697 men and 1903 women reported one or more singleton pregnancy conceived after first employment within the nuclear industry, the men reporting a total of 23,676 singleton pregnancies and the women 3585. The risks of fetal death and congenital malformation were not related to whether the father had been monitored before conception or to the dose of radiation received. Among pregnancies reported by women, the risk of early (<13 weeks of gestation) miscarriage was higher if the mother had been monitored before conception (odds ratio [OR] 1.3, 95% CI 1.0-1.6), but there was no trend with dose. The risk of stillbirth was also higher if the mother had been monitored before conception (OR 2.2, 95% CI 1.0-4.6), but the finding was based on only 29 cases (13 exposed). The risk of any major malformation, or of specific groups of malformations, was not associated with maternal monitoring, or dose received, before conception. We found no evidence of a link between exposure to low-level ionising radiation before conception and increased risk of adverse reproductive outcome in men working in the nuclear industry. Similarly for women there was no evidence of an association between monitoring before conception and malformation in offspring. The findings relating maternal preconceptual monitoring to increased risk of fetal death are equivocal and require further investigation.

Occupational cancer research in the Nordic countries.

Occupational cancer research in the Nordic countries benefits from certain structural advantages, including the existence of computerized population registries, national cancer registries with high-quality data on cancer incidence, and a personal identification number for each inhabitant. This article outlines the utilization of this research infrastructure in Denmark, Finland, Iceland, Norway, and Sweden, together with research examples from the different countries. Future research on occupational cancer in this region requires that national legislation on electronic handling of sensitive personal information should not be stricter than the European Union Directive on individual protection with regard to personal data. A personal identification number is essential both for keeping up the high quality of data of the registers and for the high quality of the process of linking the different data sources together. Although previous occupational research has focused on male workers, a broader approach is needed in the future, including a study of how cancer risk in women may be affected by occupational activity and the question of possible cancer risk in offspring of men and women exposed to workplace carcinogens.

Familial cancer risks in offspring from discordant parental cancers.

Analysis of familial cancer risks between discordant sites provides etiologic understanding on genetic and environmental risks factors of site-specific cancers. We used the Swedish nation-wide Family-Cancer Database to analyze familial risks in discordant cancers of offspring and parents. Familial risk ratios (FRRs) were calculated for cancer in offspring aged 15 to 53 years at 22 sites, discordant from parental sites. We confirmed many reported associations. Consistent novel findings associated parental-offspring sites of pancreas-breast, breast-testis and uterus-nervous system. For these, the FRRs were modest, 1.2 to 1.5 in the whole Database, but the FRRs increased in those whose parents were diagnosed before age 50. Pancreas and liver cancers showed FRRs of 2.5 to 3.3 in offspring of women and of 1.3 in offspring of men. One or both of these cancers was/were associated with cancers of stomach, colon, breast, uterus, ovary and prostate. Melanoma was associated with pancreas, breast, skin and nervous-system cancers and with leukemias. Myeloma showed a concordant FRR of about 4.0 and was associated with prostate cancer and non-thyroid endocrine-gland cancers. Mutations in known cancer-related genes may explain some of these findings, but new susceptibility genes are yet to be found. For melanoma, pancreatic and liver cancer, environmental factors are important etiologic factors and may contribute to the familial effects observed.

Male proportion in offspring of parents exposed to strong static and extremely low-frequency electromagnetic fields in Norway.

Reduced male proportion in offspring of male carbon setters prompted a study into whether offspring of workers exposed to strong static and extremely low-frequency electromagnetic fields (ELF) had a deviant sex ratio. The study was based on all births in Norway 1970-1993. The reference population was offspring of parents not exposed to ELF. The male proportion in offspring of men in aluminum works was 50.38%, RR 0.98 (0.94-1.03), in manganese works 47.32%, RR 0.92 (0.83-1.02), in factories producing iron 50.03%, RR 0.97 (0.93-1.02), in nickel works 48.27%, RR 0.94 (0.84-1.05), and in electric wire production 47.20%, RR 0.92 (0.80-1.05). In the offspring of women in aluminum works, the male proportion was 37.04%, RR 0.72 (0.59-0.90), in all smelter works grouped together, 45.13%, RR 0.88 (0.79-0.99). The male proportion in the reference population was 51.42%. The male proportion in offspring of men in industries with ELF, was slightly reduced, while offspring of women was significantly reduced.

Management of patients and subjects at risk for multiple endocrine neoplasia type 1: MEN 1. GENEM 1. Groupe d'Etude des Néoplasies Endocriniennes Multiples de type 1.

Multiple endocrine neoplasia type 1 (MEN 1) is characterized by the combined occurrence, to variable degree, of hyperparathyroidism (HPT) (85.7% of cases according to the French Registry of GENEM 1), tumors of the endocrine pancreas (49.6%), pituitary adenomas (38.4%) and, less frequently, adrenal tumors (9.6%) and neuroendocrine tumors (5.8%). Currently, diagnosis of MEN 1 is done in the fourth decade of life, but familial screening (using genetic tools whose diagnostic accuracy approaches 100%) has lowered the age of diagnosis. Screening for MEN 1 in a patient harboring an apparently sporadic tumor will depend on the endocrine gland involved. Extensive screening for MEN 1 in the presence of HPT will be conducted only when the familial history is suggestive, when parathyroid glands are hyperplastic or when multiple parathyroid adenomas have been found at surgery. All patients with an endocrine pancreas tumor need to be investigated for the presence of other endocrine lesions of MEN 1. Extensive screening for MEN 1 is only recommended when a patient with a pituitary tumor or an adrenal tumor has a familial history suggestive of MEN 1. Otherwise regular measurement of blood calcium and PTH levels seem sufficient. Extensive screening for endocrine lesions when MEN 1 is suspected involves hormone measurements and imaging procedures. For the diagnosis of HPT, calcemia and PTH 1-84 must be measured. In the absence of clinical symptoms, basal measurement of serum gastrin, glucose, insulin, glucagon, VIP, somatostatin and pancreatic polypeptide levels are combined with abdominal ultrasonography. When symptoms suggest the Zollinger-Ellison syndrome, the secretin stimulation test is recommended. The diagnosis of a pituitary tumor is made by pituitary imaging and selected hormone assays (mainly PRL). To detect an adrenal tumor, CT scan is recommended, combined with serum potassium, urinary free cortisol and androgen measurement. When the diagnosis of MEN 1 is made, clinical and hormonal follow-up (once a year) and imaging surveillance (every 3-5 years) may be sufficient to detect new other endocrinopathies (unless suggestive clinical symptoms arise). Surgical management of each endocrine lesion must be done by skilled surgeons according to therapeutic protocols which have been discussed in detail. Genetic screening is an integral part of familial screening which may be conducted in collateral and in the offspring of MEN 1 patients. Obviously ethical principles (informed consent, etc.) must be respected. As it is now possible to detect presymptomatic gene carriers with a high degree of accuracy, follow-up is needed to make appropriate management decisions. The marked anxiety provoked by screening in an overtly asymptomatic healthy subject must not be underestimated. Conversely, a negative genetic diagnosis helps to reassure the subject and avoid repetitive and costly follow-up.

Plasminogen Activator Inhibitor 1 Is Elevated in the Children of Men with Premature Myocardial Infarction

To assess whether plasminogen activator inhibitor 1 (PAI-1) activity is elevated in the progeny of young coronary men, 193 young subjects were recruited and divided into two groups. Group A consisted of 104 children whose fathers had suffered a myocardial infarction before the age of 55 ("cases"). Eighty-nine young subjects matched for age, sex, body mass index (BMI) and smoking habits without familial history of coronary artery disease (CAD) served as controls (group B). Children with a family history of diabetes mellitus or hypertension were excluded from both groups. We measured PAI-1 activity, tissue-type plasminogen activator (t-PA) antigen, a2-antiplasmin, fibrinogen, lipids and apolipoproteins in both groups. PAI-1 activity levels were also determined in the men who suffered a premature myocardial infarction 4 months after their discharge. PAI-1 activity levels were higher in cases compared to controls (3.13 +/- 1.9 vs 2.17 +/- 1.9 U/ml, p = 0.0014). t-PA antigen and a2-antiplasmin did not differ significantly between the two groups, while fibrinogen, total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B and lipoprotein(a) were significantly higher in group A. PAI-1 was positively correlated with triglycerides (r = 0.22, p = 0.024), apolipoprotein B (r = 0.21, p = 0.039) and fibrinogen (r = 0.22, p = 0.029) in cases and with BMI in both cases (r = 0.37, p = 0.0003) and controls (r = 0.23, p = 0.044). In stepwise multiple regression analysis, only apolipoprotein B (p = 0.008) and BMI (p = 0.0014) were significant determinants of PAI-1 activity in cases. There was also a positive correlation between PAI-1 activity levels of the affected fathers and their children (r = 0.30, p = 0.01). The present data support the hypothesis that elevated PAI-1 levels in the offspring of men with premature myocardial infarction impair their fibrinolytic capacity contributing to their familial predisposition to CAD.

Fibrinogen in the offspring of men with premature coronary artery disease.

We examined whether the levels of fibrinogen are elevated in the offspring of middle-aged coronary patients. One hundred and seventy-six young subjects were divided into two groups. Group A consisted of 100 children and youngsters (mean age 17 +/- 6 years) whose fathers had sustained a myocardial infarction under the age 55 years without associated history of diabetes mellitus or hypertension. Seventy-six healthy young subjects (mean age 18 +/- 5 years) matched for gender, dietary and smoking habits without familial history of coronary artery disease, diabetes mellitus or hypertension served as the control group (group B). Fibrinogen, total cholesterol, triglycerides, high and low density lipoprotein cholesterol, apolipoprotein A-1, apolipoprotein B and lipoprotein (a) were measured. Sons and daughters with a history of premature paternal myocardial infarction had higher levels of fibrinogen compared with control subjects (304.1 +/- 60 vs 274 +/- 53 mg. dl-1, P < 0.001). This difference was maintained when the above groups were divided into single sex groups. Total cholesterol, low density lipoprotein cholesterol, apolipoprotein B and lipoprotein (a) were also significantly higher in group A. Children of affected individuals who had a good lipid profile also had significantly higher fibrinogen levels compared to control group. The results support the hypothesis that the higher plasma levels of fibrinogen in the offspring of middle-aged coronary men could partially explain their predisposition for coronary artery disease. Since the levels of fibrinogen have a major genetic component, they could be a useful marker in identifying children at high risk for coronary artery disease, especially among those with no lipid abnormalities.

Apo(a) phenotypes and Lp(a) concentrations in offspring of men with and without myocardial infarction. The EARS Study. European Atherosclerosis Research Study.

In the European Atherosclerosis Research Study, genetic and environmental markers of risk of premature coronary heart disease were compared in offspring of men with and without myocardial infarction before the age of 55 years. Cases were 682 students with a paternal history of myocardial infarction, and control subjects were 1312 students without such a history. The students were enrolled in 14 universities in five European regions (Finland, Great Britain, and northern, middle, and southern Europe). Lipoprotein(a) [Lp(a)] concentrations were skewed towards lower concentrations in both cases (median, 7.3 mg/dL; 95% confidence interval, 6.3 to 8.1 mg/dL) and control subjects (median, 6.6 mg/dL; 95% confidence interval, 6.1 to 7.2 mg/dL) (P = .37). Significantly more northern European male cases than control subjects had Lp(a) levels exceeding 30 mg/dL (P = .040), but this did not pertain to females (P = .29), and overall, there was no difference between cases (16.5%) and control subjects (15.5%) in the frequency of Lp(a) concentrations above 30 mg/dL (P = .63). As expected, there was a significant (P < .01) inverse relationship between apo(a) molecular size and Lp(a) concentration. In Great Britain there was a significant difference in phenotype distribution between cases and control subjects (P = .035), due mainly to a high frequency of the apo(a) S2 isoform in cases. A similar but statistically insignificant tendency was seen in northern Europeans. In the three other regions, however, the distribution of apo(a) phenotypes among cases and controls was similar, and in the study population overall, the distribution of apo(a) phenotypes did not differ significantly (P = .74) between cases and control subjects.

The distribution of fasting plasma lipid concentrations in the offspring of men with premature coronary heart disease in Europe. The EARS Study.

Fasting plasma total cholesterol, high density lipoprotein (HDL)-cholesterol, low density lipoprotein (LDL)-cholesterol and total triglyceride was measured in 682 university students with a positive paternal history of coronary heart disease before the age of 55 years and 1312 age- and sex-matched controls recruited from 14 European centres. In male subjects, significant regional differences were observed for triglyceride (P < 0.005) and HDL-cholesterol (P < 0.05) but not for total or LDL-cholesterol. In female subjects, significant regional differences were observed for triglyceride (P < 0.05) and cholesterol (P < 0.05) but not for HDL- or LDL-cholesterol. Significant differences were observed between male cases and controls for cholesterol (P < 0.005) LDL-cholesterol (P < 0.005) and triglycerides (P < 0.005) but not for HDL-cholesterol. In females a significant difference was observed between cases and controls for LDL-cholesterol (P < 0.05) but not for total cholesterol, HDL-cholesterol or triglyceride.