Guanidine to adenine (G/A) substitution in the promoter region of the apolipoprotein AI gene is associated with elevated serum apolipoprotein AI levels in chinese non-smokers

The influence of the guanidine to adenine (G/A) substitution in the promoter region of the apolipoprotein (apo) AI gene (at ?75 bp) on serum lipids and apolipoproteins was studied in 287 healthy Chinese of both sexes in Singapore. Women had significantly higher levels of high-density lipoprotein cholesterol (HDLC) and apo AI and lower low-density lipoprotein cholesterol (LDLC). The distribution of genotypes was at Hardy-Weinberg equilibrium. The frequency of the A allele in the Chinese was significantly higher [0.27; 95% confidence interval (CI) 0.24–0.31] than that reported in Caucasians (0.12; 95% CI 0.09–0.14). In men, the A allele was associated with 20% higher apo AI; this association was completely absent in women. Furthermore, in men this association was only observed in those who had never smoked, and was absent in smokers. The G/A substitution explained 9% (P < 0.02) of the sample variance of apo AI in non-smoking men. The modulating influence of smoking could not be examined in women because too few women smoke. Although the impact of this polymorphism is modulated by hormones and smoking, it is of importance in determining levels of apo AI in healthy Chinese individuals. No association of the G/A substitution of the apo AI gene was observed with any other lipid traits. © 1994 Wiley-Liss, Inc.     

Role of genetic variation at the Apo AI-CIII-AIV gene cluster in determining plasma Apo AI levels in boys and girls

We have investigated the effect of the G/A substitution in the promoter region of the apolipoprotein (apo) AI gene (?75 bp) on plasma lipid, lipoprotein and apolipoprotein levels in a sample of 204 children from central Italy. The subjects included 111 boys and 93 girls, aged 8–11 years old. The frequency of the A allele was 0.19 in the total sample, and 0.21 and 0.17 in boys and girls, respectively. Using analysis of variance, we found the G/A substitution was significantly associated with plasma levels of total cholesterol, LDL cholesterol, apo B, and apo AI in boys, accounting for 7.0, 4.2, 5.3, and 4.3% of the sample variance, respectively. Individuals with an A allele had higher mean levels of these lipid traits than individuals homozygous for the G allele. A dietary intervention study had been carried out in a subset of these children, and the effect of the G/A substitution on plasma apo AI levels remained when boys changed to a low fat low cholesterol diet. However, no significant association was observed in girls between any of the lipid traits and the G/A genotypes. We have previously reported in this sample of children that the two polymorphisms detected with restriction enzyme PvuII, with variable sites in the first intron of the apo CIII gene (Pvu II–CIII) and the apo CIII–AIV intergenic region (Pvu II–AIV), were associated with significant differences on plasma apo AI levels. We found that the association reached statistical significance in boys only in this study. Taking these three polymorphisms together, the effects on plasma apo AI levels were additive in boys, accounting for 20.0% of the sample variance. Boys having the genotype GG/V^?V⁺ of the G/A substitution and the PvuII–AIV RFLP had mean apo AI levels 36 mg/dl lower than boys with the genotype GA + AA/V^?V^?. In girls, however, there was evidence of significant interaction of effects between the PvuII–AIV RFLP and the G/A substitution (P < 0.04), with the A allele being associated with higher levels of plasma apo AI only in girls having the rare allele (V⁺) of the PvuII–AIV RFLP. We conclude that genetic variation at the apo AI-CIII-AIV gene cluster is having a major impact on the determination of plasma apo AI levels in this sample of young boys, with additive effects due to functional changes at several places in this gene cluster detected directly (G/A) or in allelic association with the PvuII–CIII and PvuII–AIV polymorphisms. These effects are not modulated by diet but are modulated by other factors, possibly hormones, which are present in girls. © 1993 Wiley-Liss. Inc.     

Genetic factors influencing apolipoprotein AI and AII levels in a kindred with premature coronary heart disease

A single 51-member kindred, ascertained on the basis of a normotriglyceridemic proband with depressed high-density lipoprotein cholesterol (HDL-C) and myocardial infarctions at ages 40 and 42, was studied with respect to quantitative variation in HDL-C and apolipoprotein (apo) AI and AII levels. The results of bivariate segregation analysis suggest that the etiology of depressed HDL-C involves one or possibly two major loci: one has a pleiotropic effect on apo AI and apo AII levels and, possibly another one that affects apo AI levels. Both the major loci were characterized as having a dominant allele leading to depression of the respective trait(s). In addition, analysis of the cosegregation of HDL-C and apo AI levels gave evidence of residual nonfamilial factors common to both traits, leading to a positive covariance between them. This could reflect the role of apo AI in the transformation of nascent HDL-C particles into mature ones via its cofactor activity to lecithin cholesterol acyltransferase. The proposed two-locus model represents one possible etiology for the heterogeneous disorder of hypoalphalipoproteinemia. This analysis of a single pedigree does not completely define the genetic mechanism, but it does illustrate a useful new analytic approach.     

New MspI polymorphism at +83 bp of the human apolipoprotein al gene: Association with increased circulating high density lipoprotein cholesterol levels

We recently showed that loss of a MspI restriction site in the 5′-end (intron 1) of the apolipoprotein (apo) AI gene is due to a C to T transition (+83 bp) and/or a G to A transition (+84 bp). Since this region may be relevant to the regulation of apo AI gene expression and therefore to plasma high density lipoprotein cholesterol (HDL-C), we explored the association between this MspI polymorphic site and circulating HDL-C levels in 243 healthy Caucasians. There were 143 aged 18–67 years (60 males and 83 females) and 100 aged 6–12 years (58 males and 42 females). We also compared this association with a known MspI polymorphic site, a G to A transition at −75 bp of the apo AI gene. The rare allele (−) frequency for the polymorphism at +83 bp was 4.1% and 22.1% for the polymorphism at −75 bp. Subjects heterozygous for the loss of the MspI restriction site at +83 bp (genotype: M2+−, n = 20) had higher HDL-C levels than M2++ subjects (mean ± SD: 1.73 ± 0.31 vs. 1.41 ± 0.39 mmol/l, P < 0.05 for adults; 1.71 ± 0.33 vs. 1.34 ± 0.29 mmol/l, P < 0.01 for children). Adults with the G to A substitution at −75 bp also had higher HDL-C levels (1.56 ± 0.36 mmol/l for AA, 1.53 ± 0.38 mmol/l for GA, and 1.36 ± 0.38 mmol/l for GG, P < 0.05); this difference was not observed in the children. The MspI polymorphisms at both sites were in linkage disequilibrium. Their joint effect on the HDL-C levels was also significant and individuals with rare alleles (−) at both sites had the highest HDL-C levels. In an analysis of variance, the MspI polymorphism at +83 bp, and at −75 bp and gender independently accounted for 6.5%, 1.7%, and 5.9%, respectively, of the variance in circulating HDL-C levels when age was controlled as a covariate. We conclude that loss of the MspI site by the C to T (+83 bp) and/or the G to A (+84 bp) transitions is highly associated with increased HDL-C levels. The association appears to be more significant than that of the G to A transition at −75 bp. © 1996 Wiley-Liss, Inc.     

Genetic variation at the apolipoprotein gene loci contribute to response of plasma lipids to dietary change

Dietary intervention studies (from a low polyunsaturated/saturated fatty acid ratio P/S diet to a high P/S diet), carried out on a group of healthy individuals from North Karelia, Eastern Finland between 1981-1984, provided evidence that there may be a genetic component contributing to variation in response to dietary change. We have resampled blood from 107 individuals involved in the original studies and used Restriction Fragment Length Polymorphisms (RFLPs) to study the genetic contribution of variation at a number of candidate gene loci to the response to dietary change. The genes investigated in this study were the apolipoprotein (apo) genes: apo B, apo AII, apo E (protein polymorphism), apo AI-CIII-AIV gene cluster, and the LDL-receptor gene. On the basal diet the major effect of genotype on lipid traits was due to variation at the apo E gene locus; this protein polymorphism explained 14.6% of the phenotypic variance in LDL cholesterol levels and 12.7% of the phenotypic variance in total cholesterol levels. When switched to low fat high P/S diet, these effects of variation at the apo E gene locus on the phenotypic variation of LDL and total cholesterol levels disappeared. The major effect on the response to dietary change, delta, was seen on the difference in apo AI levels mediated by variation at the apo B gene locus (MspI RFLP) explaining 6.3% of the phenotypic variance in apo AI change. For the RFLPs of the apo AI-CII-AIV gene cluster, small but not significant differences on delta were found. Our results indicate that within the limits of the candidate genes studied, the major effects in response to dietary change was on apo AI levels mediated through variation at the apo B gene locus.     

Apolipoprotein E polymorphism and plasma lipid, lipoprotein, and apolipoprotein levels in Italian children.

We have investigated the effect of apolipoprotein (apo) E polymorphism on serum lipid, lipoprotein, and apolipoprotein levels in a sample of 195 children, aged 8-11 years, from Sezze, Central Italy. The relative frequencies of e2, e3, and e4 alleles were 0.062, 0.867, and 0.072, respectively. Variation at the apo E gene locus explained 5.1% of the sample variance in serum total cholesterol levels, 7.6% in low-density lipoprotein (LDL) cholesterol levels, 7.3% in apo B levels, and 14.1% in high-density lipoprotein-apo E (HDL-E) levels. The effect of the e2 allele was to lower levels of total cholesterol, LDL-cholesterol, and apo B and to raise levels of HDL-E, while the effect of the e4 allele was the opposite. Variation at the apo E gene locus was not associated with differences in serum triglyceride, HDL-cholesterol, or apo AI levels. The effects of common apo E polymorphisms and genetic variation associated with the PvuII RFLP of the apo B gene on serum apo B levels were additive, explaining 11.3% of the phenotypic variance in this sample. When the effect of apo E polymorphism on serum lipid traits was estimated in boys and girls separately, variation at the apo E gene locus explained 10.4, 13.3, 13.3, and 13.5% of the phenotypic variance in serum total cholesterol, LDL-cholesterol, apo B, and HDL-E levels, respectively, in boys, while in girls only the effect on HDL-E levels (19.3%) reached statistical significance. This study has demonstrated that genetic variations at the apo E locus contribute to the determination of serum lipid, lipoprotein, and apolipoprotein levels in youths and that the effects are gender specific.     

No common major gene for apolipoprotein A‐I and HDL3‐C levels: Evidence from bivariate segregation analysis

Apolipoprotein A‐I (apo A‐I) is the most abundant protein in high‐density lipoprotein (HDL) particles, and it plays an important role in HDL metabolism. Both apo A‐I and HDL cholesterol (HDL‐C) levels are inversely associated with risk of cardiovascular disease. Segregation analyses suggest apo A‐I levels are under the control of one or more major loci. Since HDL particles are heterogeneous in their composition and size, genetic influence on its subfractions (i.e., HDL₂ and HDL₃) could vary. A previous report showed evidence of a major locus controlling HDL₃‐C levels in a subset of the current study population. Because quantitative trait loci involved in complex diseases are likely to have pleiotropic effects on several related traits, it is possible to have a common major gene involved in regulating apo A‐I and HDL₃‐C levels. We performed a bivariate segregation analysis of apo A‐I and HDL₃‐C levels in 1,006 individuals from 137 families ascertained through probands undergoing elective, diagnostic coronary angiography at the Johns Hopkins Hospital. The results showed significant genetic correlation between these two traits, but the hypothesis of a common major gene was rejected. Bivariate segregation analysis favored a model with two genes controlling apo A‐I and a third gene independently controlling HDL₃‐C, and the genetic correlation between these two traits is due to residual additive polygenes. Overall, results from this study suggest that there are distinct genetic mechanisms for apo A‐I and HDL₃‐C levels. Future studies, especially linkage analysis, should consider distinct genetic mechanisms and multiple major gene loci. Genet. Epidemiol. 16:54–68, 1999. © 1999 Wiley‐Liss, Inc.     

Dietary fat saturation affects apolipoprotein AII levels and HDL composition in postmenopausal women.

Increased HDL-cholesterol levels have been associated with lower coronary heart disease (CHD) risk. However, HDL are heterogeneous lipoproteins, and particles enriched in apolipoprotein (Apo) AII have been associated with increased CHD risk. We examined the effect of dietary intervention on HDL composition in 14 postmenopausal women subjected to two consecutive diet periods, i.e., an oleic acid sunflower oil diet followed by a palmolein diet, each lasting 4 wk. The linoleic acid was kept at 4% total energy and the cholesterol intake at 400 mg/d. The palmolein diet increased serum total cholesterol (TC) (P < 0.001), phospholipids (P < 0.001), Apo AII (P < 0.001), HDL cholesterol (P < 0.05), HDL lipids (P < 0.05), HDL proteins (P < 0.01) and the HDL total mass (P < 0.05). The HDL cholesterol/Apo AI ratio was increased 22.0% (P < 0.05), whereas the HDL cholesterol/Apo AII and the Apo AI/Apo AII ratios were decreased 19.4% (P < 0.01) and 30.4%, (P < 0.001), respectively. When the effects of the dietary intervention were examined according to the cholesterolemia status (< or >6.2 mmol/L), the most significant changes (P < 0.001) were related to Apo AII levels. Moreover, a significant dietary oil by cholesterol level interaction was found for Apo AII and the HDL cholesterol/Apo AII ratio. In summary, a palmolein diet increased TC and HDL cholesterol compared with oleic acid sunflower oil diet; however, the increase in Apo AII but not in Apo AI suggests the impairment of reverse cholesterol transport and potentially an increase in CHD risk. This effect was more marked in women with serum TC > 6.2 mmol/L.     

Dietary intake and gene variation influence the response of plasma lipids to dietary intervention.

We have examined whether variation at the apolipoprotein (apo) B, apo E, apo AII, and apo AI-CIII-AIV genes affected the relationship between dietary intake and serum lipid traits in individuals who had participated in dietary intervention from a basal high fat diet to a low fat diet followed by a return to their natural diet, the switchback. On both the basal and switchback diets where the variance of dietary intake was great, there was a significant correlation between P/S ratio and serum total, low-density lipoprotein (LDL) cholesterol, and apo AI levels. In addition dietary cholesterol (dchol) levels correlated significantly with serum apo AI levels on the basal diet. Comparing the difference between basal and intervention (delta 1) and between switchback and intervention diets (delta 2), changes in dchol and P/S ratio correlated significantly with changes in serum total, high-density lipoprotein (HDL) and LDL cholesterol, and apo B levels. There was a significant correlation between monounsaturated fatty acid (MUFA) and apo AI levels during both changes. Furthermore we have examined whether the relationship between variables was homogeneous among genotypes of candidate gene polymorphisms. A heterogeneous effect (P less than 0.01) was seen among genotypes of the PvuII-AIV restriction fragment length polymorphism (RFLP) on the correlation of serum LDL cholesterol levels and dietary MUFA during both dietary changes (delta 1 and delta 2). A heterogeneous effect among genotypes of the apo B XbaI RFLP on the correlation between dchol versus total and LDL cholesterol during the change delta 1, but not delta 2, was observed. Thus our results show that both dietary components and genetic variation affect the response of serum lipid, lipoprotein, and apolipoprotein levels to dietary change.     

Fructose intake increases hyperlipidemia and modifies apolipoprotein expression in apolipoprotein AI-CIII-AIV transgenic mice

Fructose intake has increased steadily during the past two decades. The objective of this study was to determine the effect of fructose intake on lipid metabolism in apolipoprotein (apo) AI-CIII-AIV transgenic (Tg) mice that have severe hypertriglyceridemia and moderate hypercholesterolemia. Tg and control mice were fed for 9 mo a commercial nonpurified diet and had free access to water or 250 g/L fructose solution. In Tg mice, fructose intake increased triglycerides and cholesterol but did not induce insulin resistance. There were no differences in human hepatic apo AI and apo CIII mRNA levels in fructose-fed mice compared with untreated mice, but apo AIV mRNA was greater, indicating a differential expression of the apo AI and apo AIV genes in response to dietary perturbations. Interestingly, the plasma concentration of the three human apolipoproteins was enhanced in fructose-fed Tg mice compared with untreated Tg mice. Our data suggest that long-term fructose consumption had strong adverse effects in this hyperlipidemic mouse model.     

Multivariate genetic analysis of apo AI concentration and HDL subfractions: Evidence for major locus pleiotropy

A major locus influencing apolipoprotein AI (apo AI) serum levels was detected using data from the Donner Laboratory Family Study. This locus accounts for 46% of the phenotypic variability in apo AI levels. Multivariate segregation analysis revealed that this major locus also has significant pleiotropic effects on the relative distribution of high density lipoproteins. © 1993 Wiley-Liss, Inc.     

Genetic polymorphism of MTHFR G1793A in Chinese populations

5,10-methylenetetrahydrofolate reductase (MTHFR) is an important enzyme in folate metabolism. A novel polymorphic site in MTHFR (G1793A) could influence the homocysteine levels and was first described in 2002. Investigations revealed that this allele was associated with susceptibility to several cancers, but its distribution around the world was not adequate. To study the prevalence of the mutant frequency in Chinese populations, 923 healthy individuals from 13 Chinese populations distributing widely from north to south were collected. DNA samples were isolated from peripheral blood samples and genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), with the digestion of restriction endonuclease BsrBI. Of the 923 individuals, 82.1% were GG homozygous, 17.2% were GA heterozygous and 0.7% were AA homozygous. The frequency of the MTHFR 1793A allele in all tested individuals was 9.3%, which was slightly lower than indicated by HapMap (10%, Beiing Han, 45 samples). The frequencies of A allele were generally higher in southern China than that in northern China, and the frequencies had significant variance in 13 Chinese populations (X² = 26.315, P = 0.010). Summarizing of the MTHFR G1793A allele polymorphism, including control groups in the case–control studies, we found only 20 normal peoples with AA homozygous (7 Chineses, 1 Caucasian, 2 Java Indonesias, 2 non-Hispanic whites, 6 Irish women, 2 Indians). The Java Indonesias and Ashkenzai Jevish had the highest (26.6%) and the lowest (1.3%) 1793A frequency, respectively. Together with our previous data, the MTHFR G1793A polymorphism was in linkage disequilibrium with both C677T and A1298C polymorphism sites in Chinese population, but not as strong as presented by HapMap.     

The emerging evidence for vitamin D-mediated regulation of apolipoprotein A-I synthesis

Ischemic heart disease and cerebrovascular ischemia are leading causes of mortality in industrialized countries. The pathogenesis of these diseases involves the formation of atherosclerotic plaques with eventual rupture and superimposed thrombosis. This process is inhibited by high-density lipoprotein (HDL), the main protein component of which is apolipoprotein A-I (apo A-I). Vitamin D₃ is a hormone produced by sun-exposed skin but is acquired also in the diet. The Framingham Offspring Study and the Third National Health and Nutritional Examination Survey showed a link between vitamin D₃ intake and cardiovascular risk factors. The link between 25-hydroxyvitamin D₃ and HDL cholesterol (HDLc) and apo A-I is not as clear. Studies in vitamin D receptor knockout mice demonstrated higher HDLc and hepatic apo A-I messenger RNA expression relative to wild type. Experiments in cultured hepatocytes supported these observations. Human studies evaluating the relationship between vitamin D₃ and apo A-I and HDLc have yielded conflicting results, but most suggest a positive link between increasing vitamin D₃ levels and plasma apo A-I and HDLc. The purpose of this review is to examine the evidence linking vitamin D status and cardiovascular disease, to determine if there is a relationship between vitamin D levels and development of an atherogenic lipid profile. Our objectives are to determine if plasma vitamin D levels correlate with plasma HDLc and apo A-I and, if so, offer speculation as to how apo A-I in the context of high vitamin D levels provides enhanced atheroprotection.     

Reduction in plasma apolipoprotein E and HDL1 levels in rats with essential fatty acid deficiency

Rats were fed linoleate- or triolein-supplemented total parenteral solutions by continuous intragastric infusion for 7 or 14 d to characterize plasma lipid and apolipoprotein (apo) levels, and the high density lipoprotein (HDL) profile associated with essential fatty acid deficiency (EFAD). Results indicate that plasma cholesterol and triglyceride levels tend to be lower with EFAD, whereas plasma levels of apolipoproteins E and B are lower and apo A-I levels are higher in EFAD animals. EFAD was also associated with 30% fewer apo E--enriched HDL1 particles and a decrease from 11.4 to 11.1 nm in the mean peak diameter of HDL (P less than 0.05). These observations emphasize the sensitivity of apo E content to alterations in plasma cholesterol level and suggest that cholesterol transport is decreased during EFAD in the rat.     

Influence of polymorphisms for apolipoprotein B (ins/del,Xbal, EcoRI)and apolipoprotein E on serum lipids and apolipoproteins in a Javanese population

A total of 231 healthy subjects from a central Javanese population were investigated for the distribution of three apolipoprotein B (apo B) polymorphisms (ins/del, XbaI, and EcoRI), as well as apolipoprotein E (apo E) polymorphism in relation to serum lipid and apolipoprotein concentrations. The frequencies of the rarer alleles (del, 0.09; X⁺, 0.1; and R^?, 0.06) were lower than have been found for some Asian and European populations. Distribution of genotypes was in Hardy-Weinburg equilibrium for all the polymorphisms. A linkage disequilibrium was observed only between the ins/del and XbaI site polymorphisms of apo B (χ₄² = 25.3; P < 0.001) consistent with that observed in some other population studies. No polymorphism of the apo B gene had an association with serum lipid or apolipoprotein concentrations in this population except for XabI, which appeared to be associated with serum TG (as the log transform: R² = 8.3; F = 4.8; P < 0.01). The apo E4 allele was found to be associated with significantly higher serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDLC). Apo E polymorphism explained 5.9% of the sample variance of serum LDLC (F = 5.4; P < 0.01). © 1994 Wiley-Liss, Inc.     

Effects of chronic alcohol treatment on the synthesis, sialylation, and disposition of nascent apolipoprotein E by peritoneal macrophages of rats

BACKGROUND: Plasma apolipoprotein (apo) E, a sialoprotein, plays an important role in reverse cholesterol transport. Previously, we showed that chronic alcohol consumption impairs glycosylation of apo E in rat liver. Peritoneal macrophages are another significant apo E synthesis site. OBJECTIVE: The main purpose of this study was to determine the effects of chronic alcohol feeding of rats on the synthesis, sialylation, and sialic acid content of macrophage apo E and its ability to bind to the HDL(3) molecule in vitro. DESIGN: Rats were fed an alcoholic diet or an isoenergetic control diet for 8 wk, after which peritoneal macrophages isolated from them were cultured and analyzed for apo E metabolism. RESULTS: Macrophages from alcohol-fed rats accumulated 33.3% more (P < 0.05) cholesterol than did those from control rats when incubated with acetylated LDL. These macrophages showed a 51-57% lower relative sialylation rate of apo E (P < 0.001) but no significant difference in relative protein synthetic rate. The sialic acid content of the intracellular and secreted forms of apo E was reduced by 41.8% (P < 0.001) and 50.3% (P < 0.001), respectively, with chronic alcohol treatment. Secretion of newly synthesized apo E was impaired by 53.7% (P < 0.001) and 26. 1% (P < 0.001) in the absence and presence of HDL in the medium, respectively. Macrophages of alcohol-treated rats secreted apo E with 47.6-67.2% lower (P < 0.001) HDL(3) binding ability; binding ability was restored completely by resialylation of the desialylated apo E. CONCLUSION: In rats, an alcohol-mediated decrease in sialylation rate resulting in loss of sialic acid residues in apo E impairs the ability of apo E to bind to HDL and consequently in defective reverse cholesterol transport.     

Cholesterol and apolipoprotein distribution in plasma high-density-lipoprotein subclasses from zinc-deficient rats

Effect of zinc deficiency on the composition of plasma high-density-lipoprotein (HDL) subclasses was investigated in adult male rats (ZD) fed a diet containing 2.8 micrograms of Zn/g as compared with pair-fed (PF) and ad libitum-fed (CT) controls given 30.8 micrograms of Zn/g. Three HDL subclasses were isolated by heparin-affinity chromatography: HDL containing no apo E (HDL-E0), HDL with a moderate amount of apo E (HDL-E1), and HDL highly enriched in apo E (HDL-E2). The plasma levels of total HDL cholesterol and protein were markedly decreased in ZD. The decreases were due primarily to a significant decline in circulating HDL-E0 particles. The percent content of free cholesterol in HDL-E2 was increased in ZD compared with PF and CT. Zn deficiency decreased the plasma concentrations of apo A-I and apo C of HDL-E0 and total apo E associated with HDL-E1 and HDL-E2. The mechanisms for such changes await further investigation.     

Apolipoprotein B gene DNA polymorphisms (EcoRI and MspI) and serum lipid levels in the serbian healthy population: Interaction of rare alleles and smoking and cholesterol levels

The frequency of restriction fragment length polymorphisms (RFLPs) of the apolipoprotein B (apo B) gene, detected by EcoRI and MspI, and their influence on serum lipids were studied in a total of 239 healthy subjects from the Belgrade area. The influence of interaction between different genotypes and smoking was also studied. The relative frequency of both rare R2 and M2 alleles (lacking the cutting site) was similar to that reported in other groups of Caucasians (0.16 and 0.11, respectively). No association was observed between the apo B genotypes and serum lipid levels adjusted for age, body mass index, and blood pressure either in the whole sample or in either women or men. When smokers and non-smokers were considered separately, smoking had a significant impact on total cholesterol variability in all individuals with genotype M1M2 and high density lipoprotein (HDL) cholesterol variability in women with genotype R1R2. The presence of the rare alleles of these two polymorphisms in smokers was associated with lower lipid levels in the whole sample and in both women and men analyzed separately, except for an increase of HDL cholesterol level in male smokers, heterozygous for EcoRI polymorphism (R1R2). ©1995 Wiley-Liss, Inc.     

An epidemiological study on the familial aggregation and the sequential changes of serum lipids and apolipoproteins in school children in a rural area of Awaji Island

An epidemiological survey on serum lipids and apolipoproteins in school children in Goshiki-cho, Awaji-Island was carried out from 1985 to 1988 and their relations to blood pressure, anthropometric values, nutritional intake and a family history of hypertension were investigated. Parent-child and sibling-sibling correlations of the values were also analyzed. The results obtained were as follows: 1. During a 3-year follow-up from 11 to 14 years of age, serum levels of apo AI, apo AII, apo B and LDL cholesterol decreased at 12 years of age in both males and females. A tracking phenomenon was observed in serum levels of lipids and apolipoproteins. 2. Males at 10-14 years of age with a family history of hypertension (FH+) showed significantly higher systolic blood pressure and erythrocyte Na/K ratios than those without such a family history (FH-). The FH+ group (both males and females) had lower serum HDL cholesterol and higher levels of apo B, LDL cholesterol and triglyceride. 3. Significantly positive correlations were observed between apo AI levels of mother-son pairs and between those of elder and younger brother pairs. A positive correlation was observed between apo B levels of elder brother-younger sister pairs. Serum levels of total, HDL and LDL cholesterol in school children were closely correlated with the levels of the respective cholesterols in parents. Similar correlations were observed between sibling-sibling pairs.