The relationship between alcohol consumption and HDL cholesterol: A study of Hispanic drinking patterns

There has been very little research that has studied the effects of alcohol on biochemical markers in ethnic populations. This particular study is designed to identify the association, if any, between drinking patterns and high density lipoprotein cholesterol (HDL-C) levels in a Hispanic population. Most of what we know about the association between alcohol and HDL-C deals specifically with volume of alcohol consumed on a daily basis. Frequency, or how often alcohol consumption occurs within a given time period, is a variable that has rarely been studied. The results of this study showed how both volume and frequency of alcohol consumption affect HDL-C levels in a predominantly middle-aged Hispanic population. Ultimately, we will be able to apply these findings to future studies concerning risk of CHD in Hispanics. ^

Total cholesterol and anthropometric measurements distributions in a cross-sectional study of school children

Cross-sectional age and sex specific distributions of serum total cholesterol were described for 1091 children age 6-18 years, in The Woodlands, Texas. Associations of serum total cholesterol with five anthropometric measurements (weight, height, body mass index, arm circumference, and triceps skinfold thickness) were examined by correlation and regression analyses. Examination of serum total cholesterol distributions showed lower levels in boys than in girls for most of the age groups studied. Mean levels of total cholesterol peaked at age 9 for boys and 8 for girls. Serum total cholesterol leveled off until age 14 for boys and 11 for girls, and then dropped through age 18 for both boys and girls. These results support the hypothesis that serum total cholesterol concentration drops at pre-adolescence.^ Age adjusted correlations were observed between serum total cholesterol and triceps skinfold thickness for both boys and girls. This association was stronger in boys. Triceps skinfold thickness and arm circumference were consistently the strongest correlates for serum total cholesterol in boys. Weight and arm circumference were consistently the strongest correlates for serum total cholesterol in girls. ^

Genetic epidemiology of gallbladder disease in Mexican Americans and cholesterol 7$\alpha$-hydroxylase gene sequence variation

Among Mexican Americans, the second largest minority group in the United States, the prevalence of gallbladder disease is markedly elevated. Previous data from both genetic admixture and family studies indicate that there is a genetic component to the occurrence of gallbladder disease in Mexican Americans. However, prior to this thesis no formal genetic analysis of gallbladder disease had been carried out nor had any contributing genes been identified.^ The results of complex segregation analysis in a sample of 232 Mexican American pedigrees documented the existence of a major gene having two alleles with age- and gender-specific effects influencing the occurrence of gallbladder disease. The estimated frequency of the allele increasing susceptibility was 0.39. The lifetime probabilities that an individual will be affected by gallbladder disease were 1.0, 0.54, and 0.00 for females of genotypes "AA", "Aa", and "aa", respectively, and 0.68, 0.30, and 0.00 for males, respectively. This analysis provided the first conclusive evidence for the existence of a common single gene having a large effect on the occurrence of gallbladder disease.^ Human cholesterol 7$\alpha$-hydroxylase is the rate-limiting enzyme in bile acid synthesis. The results of an association study in both a random sample and a matched case/control sample showed that there is a significant association between cholesterol 7$\alpha$-hydroxylase gene variation and the occurrence of gallbladder disease in Mexican Americans males but not in females. These data have implicated a specific gene, 7$\alpha$-hydroxylase, in the etiology of gallbladder disease in this population.^ Finally, I asked whether the inferred major gene from complex segregation analysis is genetically linked to the cholesterol 7$\alpha$-hydroxylase gene. Three pedigrees predicted to be informative for linkage analysis by virtue of supporting the major gene hypothesis and having parents with informative genotypes and multiple offspring were selected for this linkage analysis. In each of these pedigrees, the recombination fractions maximized at 0 with a positive, albeit low, LOD score. The results of this linkage analysis provide preliminary and suggestive evidence that the cholesterol 7$\alpha$-hydroxylase gene and the inferred gallbladder disease susceptibility gene are genetically linked. ^

Low birthweight and the risk of developing subsequent high blood pressure and/or dyslipidemia in childhood

The association between birthweight and blood pressure (BP), and birthweight and serum lipid concentrations at age 7 through 11 years was examined in 1446 black and white children. The prevalence ratio (with 95% confidence interval) for being in the race-, sex- and age-specific upper decile of diastolic BP in children born with low birthweight (LBW, $<$2500 grams) versus children with birthweight $\geq$2500 grams was for black boys, 2.66 (1.24-5.70). In the other race-sex groups for diastolic BP, and in all race-sex groups for systolic BP this ratio did not differ from one. Among white boys with LBW, but not in the other race-sex groups, higher than expected percentages of subjects were in the highest decile group of triglyceride concentrations (0.01 $<$ p $<$ 0.05). The prevalence ratio was 2.42 (1.19-4.91). When prematures were excluded only more than expected white girls with LBW were in the highest decile group of triglyceride concentrations. The prevalence ratio was 3.23 (1.16-9.00). Prevalence ratios for triglyceride concentrations in black boys and girls, and for LDL/HDL-C ratio, cholesterol and VLDL-C concentrations in all race-sex groups were not different from one in analyses including and in those excluding prematures. Mean triglyceride concentrations stratified by tertiles of Quetelet Index, race and sex showed a strongly positive association between triglyceride concentrations and Quetelet Index, and in the upper tertile of the Quetelet Index an association between LBW and raised triglyceride concentrations. Multiple linear regression analyses showed that after adjusting for sex, race and age present Quetelet Index (p $<$ 0.001) is a much stronger predictor of systolic and diastolic BP, and also of LDL-C/HDL-C ratio and triglyceride concentrations in this age group than birthweight (p $>$ 0.05). Thus, an association between LBW and subsequent risk for elevated BP was confirmed for diastolic BP in black boys, but not for the other race-sex groups, and not for systolic BP in any group. This is the first study finding an association between LBW and elevated triglyceride concentrations in boys (white and black) and girls (white). A follow-up study to assess whether the findings can be confirmed at adult age is recommended. ^

THE RELATIONSHIP BETWEEN SERUM CHOLESTEROL AND CANCER INCIDENCE IN THE POPULATION OF THE HYPERTENSION DETECTION AND FOLLOW-UP PROGRAM

The relationship between serum cholesterol and cancer incidence was investigated in the population of the Hypertension Detection and Follow-up Program (HDFP). The HDFP was a multi-center trial designed to test the effectiveness of a stepped program of medication in reducing mortality associated with hypertension. Over 10,000 participants, ages 30-69, were followed with clinic and home visits for a minimum of five years. Cancer incidence was ascertained from existing study documents, which included hospitalization records, autopsy reports and death certificates. During the five years of follow-up, 286 new cancer cases were documented. The distribution of sites and total number of cases were similar to those predicted using rates from the Third National Cancer Survey. A non-fasting baseline serum cholesterol level was available for most participants. Age, sex, and race specific five-year cancer incidence rates were computed for each cholesterol quartile. Rates were also computed by smoking status, education status, and percent ideal weight quartiles. In addition, these and other factors were investigated with the use of the multiple logistic model.^ For all cancers combined, a significant inverse relationship existed between baseline serum cholesterol levels and cancer incidence. Previously documented associations between smoking, education and cancer were also demonstrated but did not account for the relationship between serum cholesterol and cancer. The relationship was more evident in males than females but this was felt to represent the different distribution of occurrence of specific cancer sites in the two sexes. The inverse relationship existed for all specific sites investigated (except breast) although a level of statistical significance was reached only for prostate carcinoma. Analyses after exclusion of cases diagnosed during the first two years of follow-up still yielded an inverse relationship. Life table analysis indicated that competing risks during the period of follow-up did not account for the existence of an inverse relationship. It is concluded that a weak inverse relationship does exist between serum cholesterol for many but not all cancer sites. This relationship is not due to confounding by other known cancer risk factors, competing risks or persons entering the study with undiagnosed cancer. Not enough information is available at the present time to determine whether this relationship is causal and further research is suggested. ^

MARITAL STATUS AND CARDIOVASCULAR RISK (SERUM, CHOLESTEROL, CIGARETTE, SMOKING, BLOOD, PRESSURE, SYSTOLIC)

There were three purposes of this study. The first was to describe the association between stable marital status and serum cholesterol, systolic blood pressure and cigarette smoking. The second purpose was to determine whether individuals who were married at one point and became widowed or divorced/separated had higher serum cholesterol, higher systolic blood pressure or were more likely to smoke prior to the change in marital status compared with individuals who did not change marital status. The third purpose was to determine whether the changes in marital status described above were related to increases in serum cholesterol or in cigarette smoking behavior. The rationale for the study was to determine whether previously reported associations between marital status categories and cardiovascular mortality may be mediated through higher values of risk correlates for cardiovascular disease among unmarried individuals.^ The study group selected for this dissertation was a sample from the Hypertension Detection and Follow-up Program (HDFP) population. The HDFP population was aged 30-69 years at the initial visit and included blacks and whites, males and females. The population was followed five years after the initial visit and periodic measurements of serum cholesterol, blood pressure and cigarette smoking behavior were obtained.^ Serum cholesterol was not associated with stable marital status category or with marital status prior to change. Changes in serum cholesterol were associated with marital status categories after change but the serum cholesterol values deceased rather than increased. Married individuals were shown to have higher serum cholesterol values compared with unmarried. Selection of the HDFP population may have influenced an ability to detect a significant association between marital status and serum cholesterol but it is doubtful that use of a general population would alter the direction of the association.^ Systolic blood pressure was significantly higher at the initial visit among unmarried white males and females compared with their married counterparts. No association between systolic blood pressure was found among black males or females. Those individuals who were married at the initial visit who experienced a change in marital status were found to have higher systolic blood pressure prior to the change in marital status. . . . (Author's abstract exceeds stipulated maximum length. Discontinued here with permission of author.) UMI ^

Characterization of the cholesterol 7$\alpha$-hydroxylase promoter in hypercholesterolemia -resistant rabbits

Our laboratory has developed and partially characterized a strain of New Zealand white rabbits that are resistant to the hypercholesterolemia which typically occurs in normal rabbits when fed a cholesterol-enriched diet. This phenotype is most likely attributed to an increase in bile acid excretion by hypercholesterolemia-resistant (CRT) rabbits as a result of elevated enzyme activity of cholesterol 7$\alpha$-hydroxylase (C7$\alpha$H), the rate-limiting enzyme in bile acid synthesis. Northern analysis revealed that CRT rabbits, in comparison to normal rabbits, have a 7-fold greater steady-state C7$\alpha$H mRNA levels irrespective of dietary regimen. The C7$\alpha$H gene in both phenotypes was determined to be a single copy gene. The hypothesis was that the elevated C7$\alpha$H mRNA levels in CRT rabbits, in comparison to normal animals, was due to an increase in the transcription rate of the C7$\alpha$H gene as a result of a mutation in a cis-acting element and/or a trans-acting factor within the hepatocyte. To isolate the C7$\alpha$H gene from both normal and CRT rabbits, genomic libraries were prepared from both phenotypes into $\lambda$GEM12 vectors using conventional techniques. Three CRT and one normal phage clones that contained the C7$\alpha$H gene were identified by screening the library with a series of probes located within different exons of the C7$\alpha$H cDNA. Sequencing analysis confirmed that approximately 1100 bp of the C7$\alpha$H 5'-flanking region from both normal and CRT phenotypes was identical. The increase in C7$\alpha$H mRNA levels was not attributed to a cis-acting mutation within this region. Liver nuclear extracts were prepared from normal and CRT rabbits maintained either on a basal or 0.25% cholesterol-enriched diet and incubated with several radiolabeled DNA fragments from the C7$\alpha$H gene. A 37 basepair region, located between nucleotides $-$452 to $-$416 was identified that had altered binding patterns between normal and CRT rabbits as a function of diet. Two additional regions, $-$747 to $-$575 and $-$580 to $-$442, produced banding patterns which were identical, irrespective of phenotype or diet. In conclusion, these studies suggested that the increase in C7$\alpha$H mRNA in CRT rabbits was due to differences in binding of a cholesterol-responsive transcription factor to the C7$\alpha$H promoter. ^