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Biomedical subjects

J D Kark

Publications and source records attributed to J D Kark.

At least 19 recordsLinked to original sources
PubMed2005

Possible association of the human KCNE1 (minK) gene and QT interval in healthy subjects: evidence from association and linkage analyses in Israeli families.

QT interval prolongation is associated with increased risk of sudden and non-sudden cardiac death. Potassium channel gene variants are associated with inherited long QT syndromes. Using linkage and association analyses, we investigated whether variants in the potassium channel subunit KCNE1 are associated with QTc intervals in an unselected population sample of 80 kindreds living in kibbutz settlements in Israel. Variance-component linkage analysis revealed weak evidence of linkage of KCNE1 polymorphisms with QTc intervals. Family-based association analysis showed a significant association between the G38S polymorphism and QTc interval. Further quantitative trait association analysis demonstrated a significant residual heritability component (h(2)= 0.33), and that the effect of the G38S variant allele is modified by gender. Estimated maximum likelihood parameters from these models indicated that male gender, age, hypertension, diabetes, hypercholesterolemia, fibrinogen and BMI were positively associated with QTc interval; level of education and cigarette smoking showed an inverse association. Both erythrocyte membrane n-6 and n-3 fatty acids showed a significant inverse association with QTc interval. While more than 15.8% of QTc variability was contributed by covariates, another 4.7% was explained by dietary factors, the G38S polymorphism explained 2.2%, and approximately 36% was explained by polygenes. An in silico analysis showed also that the novel V80 SNP, another KCNE1 synonymous variant, abolishes the recognition for a splicing enhancer, which may lead to an increased effect of the G38S mutation. These results demonstrate that, in addition to polygenic background, dietary factors and other covariables, the KCNE1 G38S variant is involved in determining QTc levels in this population-based sample of families.

Adult↗
PubMed2004

Ethnic variations in female vulnerability after an acute coronary event.

OBJECTIVE: To determine the ethnic variation of short and long term female vulnerability after an acute coronary event in a population of Chinese, Indians, and Malays. DESIGN: Population based registry. PATIENTS: Residents of Singapore between the ages of 20-64 years with coronary events. Case identification and classification procedures were modified from the MONICA (monitoring trends and determinants in cardiovascular disease) project. MAIN OUTCOME MEASURES: Adjusted 28 day case fatality and long term mortality. RESULTS: From 1991 to 1999, there were 16 320 acute coronary events, including 3497 women. Age adjusted 28 day case fatality was greater in women (51.5% v 38.6%, p < 0.001), with a larger sex difference evident among younger Malay patients. This inequality between the sexes was observed in both the pre-hospitalisation and post-admission periods. Among hospitalised patients, women were older, were less likely to have suffered from a previous Q wave or anterior wall myocardial infarction, and had lower peak creatine kinase concentrations. Case fatality was higher among women, with adjusted hazard ratios of 1.64 (95% confidence interval (CI) 1.43 to 1.88) and 1.50 (95% CI 1.37 to 1.64) for 28 day and mean four year follow up periods. There were significant interactions of sex and age with ethnic group (p = 0.017). The adjusted hazards for mortality among Chinese, Indian, and Malay women versus men were 1.30, 1.71, and 1.96, respectively. The excess mortality among women diminished with age. CONCLUSION: In this multiethnic population, both pre-hospitalisation and post-admission case fatality rates were substantially higher among women. The sex discrepancy in long term mortality was greatest among Malays and in the younger age groups.

Acute Disease↗
PubMed2003

Ethnic differences in acute myocardial infarction in Singapore.

AIMS: We compare the myocardial infarction (MI) event and mortality rates among Chinese, Malay and Indian residents of Singapore. METHODS: Residents, aged 20 to 64 years, with an MI event were identified from hospital discharge listings, postmortem reports, and the Registry of Births and Deaths. All pathology laboratories flagged patients with elevated creatine phosphokinase (CPK) levels. Modified MONICA (multinational monitoring of trends and determinants in cardiovascular disease) criteria were used for determining MI events. RESULTS: From 1991 to 1999, 12 481 MI events were identified. Chinese patients were older and less likely to have typical symptoms or previous MI. Malays had the highest peak CPK level. Among all three ethnic groups, MI event and age-adjusted case-fatality rates declined. Compared with Chinese, MI event rates were >2-fold and >3-fold higher, and age-standardized coronary mortality rates were 2.4 and 3.0 higher times for Malays and Indians, respectively. Malays have the highest 3.1-year case-fatality, with an adjusted hazard ratio of 1.26 (95% confidence interval, 1.14 to 1.38) compared with Chinese. CONCLUSION: We found strong ethnic differences in MI event, case-fatality and coronary mortality rates among the three ethnic groups in Singapore. While Indians have the greatest MI event rates, Malays have the highest case-fatality.

Adult↗
PubMed2003

Relation of parental history of coronary heart disease to obesity in young adults.

OBJECTIVE: To assess the association between obesity and parental coronary heart disease (CHD) history. DESIGN: Analysis of data from an ongoing, large-scale survey on medical status, health behaviour and attitudes. SUBJECTS: Representative samples of Israeli military personnel upon discharge from compulsory service at age 20-22 y. Overall 14297 men and 11638 women were interviewed and examined upon release from military service between 1989 and 1999. MEASUREMENTS: Data on demographic characteristics, family history of CHD, lifestyle, weight and height were collected. Analysis of variance and logistic regression were used. RESULTS: Higher mean body mass index (BMI) and obesity (BMI>30 kg/m(2)) were associated with paternal CHD history in both sexes, and with maternal CHD history among men. Offspring of a parent with a positive CHD history had a higher mean BMI (23.22 vs 22.86 kg/m(2), P<0.001) and were more likely to be obese (5.4 vs 3.7%, P<0.001) than offspring of parents with no history of CHD. Multivariate adjustment for demographic and behavioural variables associated with obesity attenuated the association (adjusted odds ratio for obesity 1.37, 95% confidence interval: 1.15, 1.64). When stratified by sex, this association remained statistically significant only among males. CONCLUSION: Young adults with a parental history of CHD are more likely to be overweight. This high-risk group should be targeted for early preventive activities.

Adult↗
PubMed2003

Combined segregation and linkage analysis of fibrinogen variability in Israeli families: evidence for two quantitative-trait loci, one of which is linked to a functional variant (-58G > A) in the promoter of the alpha-fibrinogen gene.

The association of alpha- and beta-fibrinogen polymorphisms with plasma fibrinogen levels was examined in a sample of 452 family members from 80 Israeli kindreds. The measured genotype analysis indicated that the beta-fibrinogen -455G > A polymorphism was not associated with fibrinogen levels, while the alpha-fibrinogen -58G > A locus showed a significant association with fibrinogen levels (chi2= 17.7; df = 3; p < 0.001), with the -58A allele being associated with higher levels. Segregation analysis in this sample suggested a recessive quantitative-trait locus (QTL) with a major effect that controlled the sex- and age-adjusted fibrinogen levels. Results from a combined segregation/linkage analysis indicated that a single QTL influencing plasma fibrinogen is in gametic equilibrium with the beta-fibrinogen -455G > A and alpha-fibrinogen -58G > A polymorphisms. An extended analysis with a two-QTL model significantly improved the fit of the model (p < or = 0.001), and gave support for linkage between the fibrinogen QTL and the alpha-fibrinogen polymorphism. In vitro analysis with a DNA fragment containing this variant, linked to a reporter gene, showed 2-fold higher expression of the A allele compared to the G allele in the liver cell line HepG2, both under basal conditions and after stimulation with interleukin 6. These results demonstrate that two QTLs are jointly involved in determining plasma fibrinogen levels in this sample of families, one of which is located close to a functional variant in the alpha-fibrinogen locus.

Cell Line↗
PubMed2003

Myocardial infarction risk in relation to zinc concentration in toenails.

Zn is an essential mineral. The role of Zn in atherosclerosis is not clear. Epidemiological studies, which have reported contradictory results, are limited by the use of serum Zn levels as a marker of intake. We assessed the association of toenail Zn, which integrates dietary Zn intake over 3 to 12 months, with the risk of a first myocardial infarction. Toenail Zn concentrations were determined by neutron activation analysis in the European multi-centre case-control study on antioxidants, myocardial infarction and breast cancer. This multi-centre case-control study included 684 cases and 724 controls from eight European countries and Israel. Toenail Zn levels of controls (adjusted for age and study centre) were positively associated with age, alpha-tocopherol and Se, but not with additional dietary variables or with classical risk factors for CHD. Average toenail Zn was 106.0 mg/kg in cases (95 % CI 103.1, 108.9) and 107.5 mg/kg in controls (95 % CI 104.5, 110.7). After controlling for cardiovascular risk factors and for centre, the adjusted odds ratios of myocardial infarction for quintiles 2-5 of toenail Zn with respect to the first quintile were 0.97 (95 % CI 0.59, 1.58), 1.15 (95 % CI 0.72, 1.85), 0.91 (95 % CI 0.56, 1.50), and 0.85 (95 % CI 0.52, 1.39). The P for trend was 0.45. In conclusion toenail Zn levels (reflecting long-term dietary intake) were not significantly associated with acute myocardial infarction.

Adipose Tissue↗
PubMed2002

Plasma homocysteine and parental myocardial infarction in young adults in Jerusalem.

BACKGROUND: A causal role for mildly elevated plasma homocysteine (tHcy) in cardiovascular disease remains undetermined. To address the unresolved issue of the antecedent-consequent directionality of the relationship, we assessed the familial association of tHcy with parental myocardial infarction (MI) in young Israeli men and women. We also compared tHcy concentrations in Jerusalem, where rates of coronary heart disease (CHD) are high, with the United States Third National Health and Examination Survey (NHANES III). METHODS AND RESULTS: A total of 8646 17-year-olds and 6952 parents were examined from 1976 to 1979 in Jerusalem. At ages 28 to 32 years, offspring of parents who experienced a documented MI during a 10-year follow-up (n=133 men, 62 women; 72% response) and offspring of CHD-free parents (n=389 men, 208 women; 71% response) were reexamined. tHcy levels were determined by the same laboratory for the NHANES non-Hispanic white population aged 25 to 34 years (n=379) and the Jerusalem population sample (n=858). Men from Jerusalem, but not women, had clearly higher tHcy levels than the sample from the United States (90th percentile, 23 versus 14 micromol/L). This difference was largely attributable to lower plasma vitamin B12 levels in the Israeli population. Male case offspring had higher adjusted tHcy than did controls (1.9 micromol/L, P=0.002). Logistic modeling revealed a graded increase in risk of parental MI across quintiles of offspring tHcy, with an adjusted odds ratio of 2.7 in the 5th quintile (P=0.0026 for trend). CONCLUSIONS: The higher tHcy in young male offspring of parents with CHD suggests that elevated tHcy precedes manifestation of CHD. The elevated population tHcy in men may contribute to the high incidence of CHD in Israel.

Adolescent↗
PubMed2001

Determinants of short-period heart rate variability in the general population.

Decreased heart rate variability (HRV) is associated with a worse prognosis in a variety of diseases and disorders. We evaluated the determinants of short-period HRV in a random sample of 149 middle-aged men and 137 women from the general population. Spectral analysis was used to compute low-frequency (LF), high-frequency (HF) and total-frequency power. HRV showed a strong inverse association with age and heart rate in both sexes with a more pronounced effect of heart rate on HRV in women. Age and heart rate-adjusted LF was significantly higher in men and HF higher in women. Significant negative correlations of BMI, triglycerides, insulin and positive correlations of HDL cholesterol with LF and total power occurred only in men. In multivariate analyses, heart rate and age persisted as prominent independent predictors of HRV. In addition, BMI was strongly negatively associated with LF in men but not in women. We conclude that the more pronounced vagal influence in cardiac regulation in middle-aged women and the gender-different influence of heart rate and metabolic factors on HRV may help to explain the lower susceptibility of women for cardiac arrhythmias.

Age Factors↗
PubMed2000

Coronary heart disease mortality among Arab and Jewish residents of Jerusalem.

Information on coronary heart disease (CHD) in the Palestinian population is sparse. We compared mortality rates in the largely Palestinian Arab population of Jerusalem with the Jewish population of the district between 1984 and 1997 based on official Israeli statistics. CHD mortality and all-cause mortality rates were significantly higher among Arab residents than among Jewish residents aged 35-74 years. Whether the excess CHD mortality reflects increased incidence of events, higher case fatality, or both remains to be established. Possible explanations include a higher prevalence of conventional risk factors such as diabetes, obesity, and smoking in Palestinians, stress effects related to the complex political situation and socioeconomic inequalities, and suspected differences in medical care.

Adult↗
PubMed2000

Taq1B CETP polymorphism, plasma CETP, lipoproteins, apolipoproteins and sex differences in a Jewish population sample characterized by low HDL-cholesterol.

Mean high-density lipoprotein cholesterol (HDL-C) concentrations are low in the Jewish population of Israel. With this in mind we assessed the association of the Taq1B CETP polymorphism, plasma CETP mass and plasma lipid, lipoprotein and apolipoprotein concentrations in a sample of 884 Jerusalem residents aged 28-32. The allele frequency (0.435 +/- 0.017(S.E.)) is similar to that reported elsewhere. There was a strong (apparently codominant) association of the Taq1 B allele with plasma CETP in both sexes, and an inverse association with HDL-C and apo A-1, significant in women and undiminished upon adjustment for plasma CETP. There was evidence in this population for an admixture of two plasma CETP distributions, with 9% belonging to a distribution with the higher mean, pointing to a possible major gene effect. Mean plasma CETP was higher in women than men. Plasma CETP was inversely associated with HDL-C in men but not in women (P< 0.05 for the sex difference, multivariate analysis), inversely related to the HDL-C/apo A-1 ratio in men and positively related in women (P < 0.005 for the sex difference), and was positively associated with total cholesterol (TC) and low-density lipoprotein cholesterol in both sexes, and with the TC/HDL-C ratio and apo B in men alone. The sex differences may reflect dissimilarities in the regulatory function of CETP in lipid exchange. The absence of an unusual allele frequency of the Taq1B CETP polymorphism and its relatively modest association with HDL-C argue against an important role for this or strongly linked sites in determining the low population levels of HDL-C in Israel.

Alleles↗
PubMed2000

Helicobacter pylori infection and subsequent peptic duodenal disease among young adults.

BACKGROUND: Evidence for a causal relationship between presence of Helicobacter pylori (H. pylori) in gastric mucosa and development of peptic disease is based largely on intervention studies in which eradication of H. pylori led to healing of the lesion. The aim of this study was to assess the importance of H. pylori seropositivity for subsequent development of peptic disease in a prospective study design in young Israelis. METHODS: A nested case-control serum bank study based on a systematic sample of male and female inductees to the Israel Defense Force. Twenty-nine cases of duodenal ulcer or duodenitis of moderate or higher severity, diagnosed between 1986 and 1995, were individually matched for age, sex, ethnicity, education and year of induction, with five healthy controls each. Presence of anti-H. pylori antibodies in the frozen stored sera was determined by ELISA. RESULTS: The geometric mean titre of anti-H. pylori antibodies at baseline was significantly higher in cases (18. 3 U/ml) than controls (6.9 U/ml; P = 0.009). The matched odds ratio for peptic ulcer disease by seropositivity was 3.8 (95% CI : 1.4-10. 2). A stronger association was evident for subjects diagnosed > or =2 years after induction than those diagnosed earlier. The population attributable fraction was 56.6% (95% CI : 15.7-81.1). CONCLUSIONS: Pre-existing infection with H. pylori, as determined by seropositivity, is an important determinant of development of duodenal ulcer or duodenitis in young Israelis, supporting the generalizability of an apparent causal association to diverse populations.

Adolescent↗
PubMed1999

Nonfasting plasma total homocysteine level and mortality in middle-aged and elderly men and women in Jerusalem.

BACKGROUND: Elevated plasma total homocysteine level has been associated with cardiovascular disease in many studies, mostly in Europe and North America. Data on persons from other areas and on associations with overall mortality are sparse. OBJECTIVE: To determine the relation of plasma homocysteine level to all-cause and cause-specific mortality. DESIGN: Prospective observational study with 9- to 11-year follow-up. SETTING: A free-living, multiethnic Jewish population in western Jerusalem, Israel. PARTICIPANTS: 1788 residents of Jerusalem (808 men and 980 women) who were at least 50 years of age and were examined between 1985 and 1987 as part of the Kiryat Yovel Community Health Study. MEASUREMENTS: Nonfasting plasma homocysteine level was determined in frozen stored samples. Deaths during follow-up were identified by linkage with the national population registry. RESULTS: Plasma homocysteine levels exceeded 14 micromol/L in 28% of men and 20% of women. During the study period, 405 deaths occurred. In multivariate Cox models that controlled for possible confounders, a nonmonotonic increase in mortality hazard ratios was associated with ascending quintile of homocysteine level: 1.0, 1.4, 1.3, 1.5, and 2.0 (P < 0.001 for trend). The relation was similar for cardiovascular and noncardiovascular causes of death (excluding cancer). The association was weaker when deaths that occurred during the first 5 years of follow-up were excluded; corresponding hazard ratios for ascending quintile of homocysteine level were 1.0, 1.0, 1.2, 1.1, and 1.6 (P = 0.063 for trend). Age- and sex-adjusted percentages of deaths "attributable" to elevated plasma homocysteine level (> or = 14 micromol/L) were 12.5% (95% CI, 6.7% to 18.8%) for all deaths, 16.0% (CI, 7.2% to 25.6%) for deaths during the first 5 years of follow-up, and 8.3% (CI, 1.5% to 16.1%) for later deaths. CONCLUSIONS: A mildly to moderately elevated nonfasting plasma homocysteine level is a substantial risk marker for death from all causes. The association seems to be stronger during the first 5 years of follow-up.

Aged↗
PubMed1999

Inheritance of LDL peak particle diameter: results from a segregation analysis in Israeli families.

Genetic and environmental determinants of LDL peak particle diameter (LDL-PPD) were investigated in a sample of 80 kindreds residing in kibbutz settlements in Israel. The sample included 182 males and 191 females ages 15-93 years. LDL-PPD levels were first adjusted for variability in sex and age. Commingling analysis demonstrated that a mixture of two normal distributions fit the adjusted LDL-PPD levels better than did a single normal distribution. Complex segregation analysis was first applied to these sex and age adjusted data but was not conclusive. However, when the regression model for sex and age allowed coefficients to be ousiotype (class) specific, the mixed environmental model was rejected while a major Mendelian model was not. These results suggest that the particular genotypes determined by the major gene, which are associated with different phenotypic variances, are likely to be more realistic, and that this analytic approach can contribute to improving our understanding of the genetics of LDL particle size.

Adolescent↗
PubMed1999

Inheritance of heart rate variability: the kibbutzim family study.

Heart rate variability (HRV) measures are associated with coronary heart disease incidence and mortality. Therefore insight into the genetic and environmental determinants of these measures may have clinical relevance. We assessed the role of genetic and environmental factors of time domain and frequency domain HRV indices. Participants were 451 kibbutz members, aged 15 and up, belonging to 80 families. HRV indices were calculated from Holter recordings measured over 5 min. Our data indicate that for the two time- and four frequency domain indices, a mixture of two normal distributions fit the data significantly better than a single normal distribution (P<0.05). We used complex segregation analysis to infer the modes of inheritance of these HRV measures. We found evidence for possible involvement of a recessive major gene in the inheritance of the root mean square of successive differences in RR intervals (RMSSD), which is predominantly vagally mediated. A putative major gene explains 28%-34% of the adjusted inter-individual variability. The SD, determined by a mixture of mechanisms, is influenced by environmental and polygenic effects, but not by a major gene. The findings regarding the heritability of the frequency domain indices were not conclusive. However, the involvement of genetic factors was not rejected. Additional studies in extended families are needed to confirm the involvement of major genes in the determination of the autonomic activity.

Adolescent↗
PubMed1999

Genetic and environmental sources of QT interval variability in Israeli families: the kibbutz settlements family study.

QT interval prolongation not attributed to long QT syndromes is reported to be associated with increased risk of sudden and nonsudden cardiac death. Genetic and environmental determinants of QTc interval were investigated in an unselected free living population sample of 80 kindreds residing in kibbutz settlements in Israel. The sample included 214 males and 227 females aged 15-97 years. There was a significant familial aggregation of adjusted QT interval levels, as indicated by inter- and intraclass correlation coefficients significantly different from zero. Complex segregation analysis applied to the sex- and age-adjusted data was not conclusive and heterogeneous etiologies for individual differences were suggested. There was evidence for a single recessive locus (q = 0.173) with a major effect in addition to polygenic effects (h2 = 0.41) that explained the mixture of distributions. In parallel, a nontransmitted environmental major factor in addition to polygenic effects that explained the adjusted variation in QTc could not be rejected. Similar results were obtained upon the adjustment for sex, age, and environmental covariables. The major factor, either genetic or environmental, and polygenic-loci accounted for about 20 and 33% of the adjusted QTc variation, respectively. Furthermore, sex, age, measured environmental covariables, the unmeasured major factor, and the unmeasured polygenes could account for 63% of the variation of QTc in these families. Our data provide evidence for a major factor, either genetic or environmental, in addition to a polygenic background, influencing QT interval levels in a population-based sample of pedigrees.

Adolescent↗
PubMed1999

Omega-3 fatty acids in adipose tissue and risk of myocardial infarction: the EURAMIC study.

Omega-3 fatty acids have potential antiatherogenic, antithrombotic, and antiarrhythmic properties, but their role in coronary heart disease remains controversial. To evaluate the association of omega-3 fatty acids in adipose tissue with the risk of myocardial infarction in men, a case-control study was conducted in eight European countries and Israel. Cases (n=639) included patients with a first myocardial infarction admitted to coronary care units within 24 hours from the onset of symptoms. Controls (n=700) were selected to represent the populations originating the cases. Adipose tissue levels of fatty acids were determined by capillary gas chromatography. The mean (+/-SD) proportion of alpha-linolenic acid was 0.77% (+/-0.19) of fatty acids in cases and 0.80% (+/-0.19) of fatty acids in controls (P=0.01). The relative risk for the highest quintile of alpha-linolenic acid compared with the lowest was 0.42 (95% confidence interval [CI] 0.22 to 0.81, P-trend=0.02). After adjusting for classical risk factors, the relative risk for the highest quintile was 0.68 (95% CI 0.31 to 1.49, P-trend=0.38). The mean proportion of docosahexaenoic acid was 0.24% (+/-0.13) of fatty acids in cases and 0.25% (+/-0.13) of fatty acids in controls (P=0. 14), with no evidence of association with risk of myocardial infarction. In this large case-control study we could not detect a protective effect of docosahexaenoic acid on the risk of myocardial infarction. The protective effect of alpha-linolenic acid was attenuated after adjusting for classical risk factors (mainly smoking), but it deserves further research.

Adipose Tissue↗