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PubMed2000

Gene-diet interactions in obesity.

A considerable amount of research on the genetics of obesity has been reported in the past few years. Despite evidence that genetic factors play a significant role in the etiology of this nutritional disease and the increasing number of obesity genes identified, relatively little is known about the role of genes in the response of obesity phenotypes to alterations in energy balance or diet composition. This is especially true for dietary fat, which is known to be associated with obesity at the population level. The aim of this review was to summarize the evidence currently available about the role of gene-nutrient interactions in human obesity. Evidence from both genetic epidemiology and molecular epidemiology studies suggests that genetic factors are involved in determining the susceptibility to gaining or losing fat in response to diet or the risk of developing some of the comorbidities generally observed in obese individuals. Recent evidence suggests that quantitative trait loci identified from animal models of diet-induced obesity could influence body fat in humans. Despite the limited number of studies, the evidence on gene-diet interactions in obesity is convincing. More research is needed to identify the genes responsible for these interaction effects, and the use of animal models of diet-induced obesity represents a promising approach. Finally, data on children are needed to allow assessment of the tracking of nutrient intake between childhood and adulthood. In addition, gene-diet interactions in children need to be investigated to determine whether the genes involved are the same as those found in adults.

Animals↗

PubMed2001

Gene-diet interaction and plasma lipid response to dietary intervention.

Research in the field of gene-diet interactions as determinants of plasma lipid response to dietary interventions has accumulated a substantial body of evidence during the past decade. Several candidate genes have shown some promise as potential markers of individual dietary responsiveness. Among the best characterized are the APOE, APOA4, APOB, APOC3, and LPL loci. Other genes are being continuously incorporated to this most interesting search. However, in very few cases has consensus been achieved about the usefulness of genetic markers as clinically significant predictors of dietary response. The increased ability to generate genotypic information, in combination with the knowledge from the human genome project and more comprehensive experimental designs, will dramatically improve our capacity to answer many of our current questions. It will also help to prove that knowledge of an individual's genetic background will facilitate more precise dietary counseling and intervention, and more efficacious primary and secondary coronary heart disease prevention.

Apolipoproteins↗

PubMed1995

Gene-diet interaction in determining plasma lipid response to dietary intervention.

It has long been known that there is an extremely high degree of variability in both human and nonhuman primates in terms of low density lipoprotein cholesterol (LDL-C) lowering in response to restriction of dietary saturated fat and cholesterol. In this regard we have reviewed the current knowledge regarding the gene-diet interaction in relation to plasma lipid response to dietary intervention. Several candidate gene loci have been examined in humans: apolipoprotein (apo) A-I, apo A-IV, apo B, apo C-III and apo E, as well as lipoprotein lipase (LPL). Several mutations at these loci have been found to be associated with responsiveness. We and others have documented that subjects carrying the apo E4 allele are more responsive with regard to LDL-C lowering in response to dietary fat and cholesterol restriction than subjects carrying the apo E3 or apo E2 alleles, whereas some studies report no association of apo E phenotypes with lipid response to some dietary interventions. Our own meta-analysis indicates that apo E genotype effects are modulated via alterations of amount and type of dietary fat. We have also documented that subjects carrying the common glutamine for histidine mutation at amino acid 360 of apo A-IV are significantly less responsive in terms of LDL-C lowering than subjects with the normal apo A-IV genotype is modulated via changes in dietary cholesterol. In addition, we have documented that the common G/A mutation within the promoter region of the apo A-I gene is associated with greater responsiveness of LDL-C to dietary fat alterations. The XbaI and insertion/deletion polymorphisms at the apo B gene locus and the HindIII restriction fragment length polymorphism (RFLP) at the LPL locus have also been associated with diet responsiveness. Therefore, in humans these gene loci account for a significant portion of the variability in plasma lipid response to dietary alterations.

Animals↗

PubMed2001

Gene-diet interactions and plasma lipoproteins: role of apolipoprotein E and habitual saturated fat intake.

To test whether plasma lipoprotein levels and low density lipoprotein (LDL) particle size are modulated by an interaction between habitual saturated fat intake and apolipoprotein E (APOE) genotype, we studied 420 randomly selected free-living Costa Ricans. The APOE allele frequencies were 0.03 for APOE2, 0.91 for APOE3, and 0.06 for APOE4. The median saturated fat intake, 11% of energy, was used to divide the population into two groups, LOW-SAT (mean intake 8.6% energy) represents those below median intake, and HIGH-SAT (mean intake 13.5%) represents those above median intake. Significant interactions between APOE genotype and diet were found for VLDL (P = 0.03) and HDL cholesterol (P = 0.02). Higher saturated fat intake was associated with higher VLDL cholesterol (+29%) and lower HDL cholesterol (-22%) in APOE2 carriers, while the opposite association was observed in APOE4 carriers (-31% for VLDL cholesterol and +10% for HDL cholesterol). Higher saturated fat intake was associated with smaller LDL particles (-2%, P < 0.05) in APOE2 carriers, and larger LDL particles (+2%, P < 0.05) in APOE4 carriers, but the gene-diet interaction was not statistically significant (P = 0.09). Higher saturated fat intake was associated with higher LDL cholesterol in all genotypes (mean +/- SEM, LOW-SAT 2.61 +/- 0.05 vs. HIGH-SAT 2.84 +/- 0.05 mmol/L, P = 0.009). These data suggest that the APOE2 allele could modulate the effect of habitual saturated fat on VLDL cholesterol and HDL cholesterol in a population with an average habitual total fat intake of less than 30%.

Adult↗

PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗

PubMed2003

Gene-diet interactions in brain aging and neurodegenerative disorders.

While there are many examples of people who live for 100 years or more with little evidence of a decline in brain function, many others are not so fortunate and experience a neurodegenerative disorder, such as Alzheimer disease or Parkinson disease. Although an increasing number of genetic factors that may affect the risk for neurodegenerative disorders are being identified, emerging findings suggest that dietary factors play major roles in determining whether the brain ages successfully or experiences a neurodegenerative disorder. Dietary factors may interact with disease-causing or predisposing genes in molecular cascades that either promote or prevent the degeneration of neurons. Epidemiologic findings suggest that high-calorie diets and folic acid deficiency increase the risk for Alzheimer disease and Parkinson disease; studies of animal models of these disorders have shown that dietary restriction (reduced calorie intake or intermittent fasting) and dietary supplementation with folic acid can reduce neuronal damage and improve behavioral outcome. Animal studies have shown that the beneficial effects of dietary restriction on the brain result in part from increased production of neurotrophic factors and cytoprotective protein chaperones in neurons. By keeping homocysteine levels low, folic acid can protect cerebral vessels and prevent the accumulation of DNA damage in neurons caused by oxidative stress and facilitated by homocysteine. Although additional studies are required in humans, the emerging data suggest that high-calorie diets and elevated homocysteine levels may render the brain vulnerable to age-related neurodegenerative disorders, particularly in persons with a genetic predisposition to such disorders.

Aging↗

PubMed2002

Polyunsaturated fatty acids modulate the effects of the APOA1 G-A polymorphism on HDL-cholesterol concentrations in a sex-specific manner: the Framingham Study.

BACKGROUND: A common G-to-A substitution in the promoter area (-75 base pairs) of the apolipoprotein A-I gene (APOA1) has been described. The A allele was shown to be associated with higher HDL-cholesterol concentrations in some studies but not in others. OBJECTIVE: We examined whether dietary fat modulates the association between this polymorphism and HDL-cholesterol concentrations. DESIGN: We studied a population-based sample of 755 men and 822 women from the Framingham Offspring Study. RESULTS: The frequency of the A allele was 0.165. No significant differences were observed between G/G subjects and carriers of the A allele for any lipid variables. In multivariate linear regression models, HDL-cholesterol concentrations in women were associated with a significant interaction between polyunsaturated fatty acid (PUFA) intake as a continuous variable and APOA1 genotype (P = 0.005). By using 3 categories of PUFA intake, we found a significantly different effect of APOA1 genotype across PUFA categories in women. When PUFA intake was <4% of energy, G/G subjects had approximately 14% higher HDL-cholesterol concentrations than did carriers of the A allele (P < 0.05). Conversely, when PUFA intake was >8%, HDL-cholesterol concentrations in carriers of the A allele were 13% higher than those of G/G subjects (P < 0.05). No significant allelic difference was observed for subjects in the range of PUFA intake of 4-8% of energy. These interactions were not significant in men. CONCLUSIONS: We found a significant gene-diet interaction associated with the APOA1 G-A polymorphism. In women carriers of the A allele, higher PUFA intakes were associated with higher HDL-cholesterol concentrations, whereas the opposite effect was observed in G/G women.

Adult↗

PubMed2003

The T111I mutation in the EL gene modulates the impact of dietary fat on the HDL profile in women.

The objective of the present study was to examine the impact of the T111I missense mutation in exon 3 of the endothelial lipase (EL) gene on HDL and its potential interaction effect with dietary fat. The study sample included 281 women and 216 men aged between 17 and 76 years from the Québec Family Study. Plasma HDL3-C levels of I111I homozygote women were higher compared with those of women carrying the wild-type allele (P = 0.03). These differences were not attenuated when adjusted for levels of obesity and were not observed among men. Dietary PUFA interacted with the T111I mutation to modulate apolipoprotein A-I (apoA-I) and HDL3-C levels among women. Specifically, a diet rich in PUFA was associated with increased apoA-I levels among women carriers of the I111 allele and with decreased apoA-I among women homozygotes for the wild-type allele (P = 0.002). A similar interaction was observed with plasma HDL3-C levels (P = 0.003). These interactions were not observed among men. In conclusion, the EL T111I mutation appears to have a modest effect on plasma HDL levels. The gene-diet interaction among women, however, suggests that the T111I missense mutation may confer protection against the lowering effect of a high dietary PUFA intake on plasma apoA-I and HDL3-C levels.

Adipose Tissue↗

PubMed2003

Dietary fat interacts with the -514C>T polymorphism in the hepatic lipase gene promoter on plasma lipid profiles in a multiethnic Asian population: the 1998 Singapore National Health Survey.

We have previously reported an interaction between -514C>T polymorphism at the hepatic lipase (HL) gene and dietary fat on high-density lipoprotein-cholesterol (HDL-C) metabolism in a representative sample of white subjects participating in the Framingham Heart Study. Replication of these findings in other populations will provide proof for the relevance and consistency of this marker as a tool for risk assessment and more personalized cardiovascular disease prevention. Therefore, we examined this gene-nutrient interaction in a representative sample of Singaporeans (1324 Chinese, 471 Malays and 375 Asian Indians) whose dietary fat intake was recorded by a validated questionnaire. When no stratification by fat intake was considered, the T allele was associated with higher plasma HDL-C concentrations (P = 0.001), higher triglyceride (TG) concentrations (P = 0.001) and higher HDL-C/TG ratios (P = 0.041). We found a highly significant interaction (P = 0.001) between polymorphism and fat intake in determining TG concentration and the HDL-C/TG ratio (P = 0.001) in the overall sample even after adjustment for potential confounders. Thus, TT subjects showed higher TG concentrations only when fat intake supplied >30% of total energy. This interaction was also found when fat intake was considered as continuous (P = 0.035). Moreover, in the upper tertile of fat intake, TT subjects had 45% more TG than CC individuals (P < 0.01). For HDL-C concentration, the gene-diet interaction was significant (P = 0.015) only in subjects of Indian origin. In conclusion, our results indicate that there are differences in the association of -514C>T polymorphism with plasma lipids according to dietary intake and ethnic background. Specifically, the TT genotype is associated with a more atherogenic lipid profile when subjects consume diets with a fat content > 30%.

Asian People↗

PubMed2002

Brassica, biotransformation and cancer risk: genetic polymorphisms alter the preventive effects of cruciferous vegetables.

The chemoprotective effect of cruciferous vegetables is due to their high glucosinolate content and the capacity of glucosinolate metabolites, such as isothiocyanates (ITC) and indoles, to modulate biotransformation enzyme systems (e.g., cytochromes P450 and conjugating enzymes). Data from molecular epidemiologic studies suggest that genetic and associated functional variations in biotransformation enzymes, particularly glutathione S-transferase (GST)M1 and GSTT1, which metabolize ITC, alter cancer risk in response to cruciferous vegetable exposure. Moreover, genetic polymorphisms in receptors and transcription factors that interact with these compounds may further contribute to variation in response to cruciferous vegetable intake. This review outlines the metabolism and mechanisms of action of cruciferous vegetable constituents, discusses the recent human studies testing effects of cruciferous vegetables on biotransformation systems and summarizes the epidemiologic and experimental evidence for an effect of genetic polymorphisms in these enzymes on response to cruciferous vegetable intake. Taken together, genetic differences in biotransformation enzymes and the factors that regulate them, as well as variation in glucosinolate content of cruciferous vegetables and the methods used to prepare these foods underscore the multiple layers of complexity that affect the study of gene-diet interactions and cancer risk in humans.

Biotransformation↗

PubMed2002

Polymorphisms in candidate obesity genes and their interaction with dietary intake of n-6 polyunsaturated fatty acids affect obesity risk in a sub-sample of the EPIC-Heidelberg cohort.

BACKGROUND/AIM: In several genes coding for molecules involved in the regulation of body weight (fat mass) and thermogenesis, polymorphisms have been reported which possibly modify human obesity risk. The aim of this study was a) to reproduce these observations with data and biological material from the Heidelberg cohort of EPIC, a large European prospective investigation into diet and cancer, and b) to investigate potential effects of interactions between dietary fatty acid intake and allelic variants on obesity risk. SUBJECTS AND METHODS: Within EPIC-Heidelberg, 154 subjects with a body mass index > 35 kg/m(2) and 154 age- and sex-matched normal-weight controls were selected and genotypes determined for 11 candidate genes. Dietary intake was assessed by a validated food frequency questionnaire. Odds ratios (OR) were computed by means of unconditional logistic regression and different adjustment models. Genotyping was performed by PCR-RFLP and allele-specific PCR. RESULTS: For most of the investigated genes (PPARA, PPARG2, UCP1, UCP2, UCP3, BAR-2, APM1, leptin, SORBS1, HSL, and TNFA) an indication for a minor effect on obesity risk was found. Indication of a risk-increasing effect was strongest for the homozygous form of leptin -2548AA with an adjusted OR of 3.53 (p < 0.009). Additionally, for the polymorphic sites of BAR-2 (Arg16Gly and Gln27Glu) a significant effect on obesity risk was seen. Importantly, the results of the analysis of gene-diet interactions suggest that the allelic variants of candidate genes (leptin, TNFA, PPARG2) might strongly affect diet-related obesity risk. CONCLUSIONS: The results support some but not all previous reports about a risk-modulating effect of polymorphisms in genes affecting obesity risk. The most important finding is an indication of substantial interaction between allelic variants of particular genes and fatty acid intake-related obesity risk. These observations suggest that future studies on polymorphisms in obesity genes should take data on dietary habits into account.

Adult↗

PubMed2026

Diet-responsive proteogenomic effects following short-term restriction of animal products in humans.

The effect of diet on genetic regulation in humans remains largely unexplored. Here, we investigate gene-diet interactions in a unique group of healthy individuals (N = 200) who alternate between omnivory and dietary restriction of animal products for religious reasons. Using longitudinal proteomic and genotype data, we identify diet-responsive cis-pQTLs and highlight regulatory effects on LBR and MSRA, proteins involved in cholesterol and methionine metabolism respectively. LBR-associated cis-pQTL rs74148404 colocalizes with obesity exclusively under dietary restriction, suggesting diet-dependent modulation of genetic risk. We also show that a diet-dependent cis-pQTL for metabolic regulator FGF21 colocalizes with eosinophil and platelet traits pointing to diet-sensitive immunometabolic signalling. By parallel profiling of a continuously omnivorous control group (N = 211), we uncover seasonally dynamic genetic regulation for proteins linked to apoptosis in immune system pathways (MAVS, CASP3, PDLIM7, IL12RB1), effects likely masked by animal product restriction. These findings reveal dynamic diet- and season-sensitive regulatory mechanisms with implications for precision nutrition and individualized disease prevention strategies, and underscore the need to integrate environmental context into genetic studies of health and disease.

Humans↗

PubMed2002

Relationship of genetic variation in genes encoding apolipoprotein A-IV, scavenger receptor BI, HMG-CoA reductase, CETP and apolipoprotein E with cholesterol metabolism and the response to plant stanol ester consumption.

BACKGROUND: Differences in genetic constitution may affect cholesterol metabolism and responses to diet. Identification of common variations in genes related to dietary responsiveness is therefore an attractive goal to be able to prescribe individually tailored diets for the treatment of dyslipidaemia. MATERIALS AND METHODS: We have examined relationships between serum lipids and lipoproteins, cholesterol-standardized campesterol and lathosterol concentrations with genetic variation, and the presence of a gene-diet interaction between plant stanol ester consumption. Candidate genes were apolipoprotein A-IV (apoA-IV), scavenger receptor-BI (SR-BI), cholesterol ester transfer protein (CETP), 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, and apolipoprotein E (apoE). These relations were examined in 112 nonhypercholesterolaemic subjects, of whom 70 consumed 3.8-4.0 g plant stanol esters a day for 8 weeks. RESULTS: At baseline, high-density lipoprotein (HDL) concentrations of 1.56 +/- 0.36 mmol L(-1) in SR-BI-2 allele carriers tended to be lower compared to the 1.72 +/- 0.42 mmol L(-1) in SR-BI-1/1 subjects (P = 0.069). Cholesterol standardized lathosterol concentrations were also lower in the SR-BI-2 allele carriers (P = 0.002). Furthermore, low-density lipoprotein (LDL) cholesterol concentrations in apoE2 subjects, were lower compared to the LDL cholesterol concentration in apoE3 group (P = 0.002) and apoE4 subjects (P < 0.001). No significant differences between the polymorphisms and dietary responsiveness to plant stanol ester consumption could be found, which indicates that it is unlikely that one of the single polymorphisms analysed in this study is a major factor in explaining the variation in serum LDL cholesterol responses. CONCLUSION: These findings suggest that all subjects who want to lower their cholesterol concentration, will benefit from plant stanol ester consumption, irrespective of their apoA-IV, SR-BI, HMG-CoA reductase, CETP, or apoE genotype.

Adult↗

PubMed1999

The genetics of serum lipid responsiveness to dietary interventions.

CHD is a multifactorial disease that is associated with non-modifiable risk factors, such as age, gender and genetic background, and with modifiable risk factors, including elevated total cholesterol and LDL-cholesterol levels. Lifestyle modification should be the primary treatment for lowering cholesterol values. The modifications recommended include dietary changes, regular aerobic exercise, and normalization of body weight. The recommended dietary changes include restriction in the amount of total fat, saturated fat and cholesterol together with an increase in the consumption of complex carbohydrate and dietary fibre, especially water-soluble fibre. However, nutrition scientists continue to question the value of these universal concepts and the public health benefits of low-fat diets, and an intense debate has been conducted in the literature on whether to focus on reduction of total fat or to aim efforts primarily towards reducing the consumption of saturated and trans fats. Moreover, it is well known that there is a striking variability between subjects in the response of serum cholesterol to diet. Multiple studies have examined the gene-diet interactions in the response of plasma lipid concentrations to changes in dietary fat and/or cholesterol. These studies have focused on candidate genes known to play key roles in lipoprotein metabolism. Among the gene loci examined, APOE has been the most studied, and the current evidence suggests that this locus might be responsible for some of the inter-individual variability in dietary response. Other loci, including APOA4, APOA1, APOB, APOC3, LPL and CETP have also been found to account for some of the variability in the fasting and fed states.

Apolipoprotein C-III↗

PubMed1997

The effect of short-term fasting, apolipoprotein E gene polymorphism, and sex on plasma lipids.

The effect of 1 wk of supervised fasting on plasma lipid concentrations in subjects with different apolipoprotein E (apo E) phenotypes was studied in 58 healthy free-living volunteers. The participants consumed an 870-kJ(208 kcal)/d liquid diet containing fruit and berry juices, tea, and water. The decline in plasma total cholesterol during 1 wk of fasting was 0.46 mmol/L in women and 0.35 mmol/L in men. The decreases were significant in both women and men. The response patterns of plasma total cholesterol were not significantly different between the sexes. In men, the changes in plasma low-density-lipoprotein cholesterol during the fast differed significantly (P = 0.0181) between the apo E phenotypes, whereas in women there were no differences due to phenotype (P = 0.695). The magnitude of the change in plasma triacylglycerol during the fast was different between the sexes (P = 0.0099). The changes in plasma triacylglycerols differed significantly between apo E phenotype groups in men (P = 0.0295) but not in women (P = 0.0661). Statistical comparison between different apo E phenotypes was performed with and without the small apo E3,2+E2,2 group, with essentially similar results. During fasting, plasma high-density-lipoprotein cholesterol concentrations decreased slightly but not significantly. The study shows significant differences in the associations of apo E alleles and sex on plasma lipid responses during fasting and illustrates the importance of gene-diet interactions in the regulation of lipid metabolism in humans.

Apolipoproteins E↗

PubMed2002

Dietary isothiocyanates, glutathione S-transferase polymorphisms and colorectal cancer risk in the Singapore Chinese Health Study.

Dietary intake of cruciferous vegetables (Brassica spp.) has been inversely related to colorectal cancer risk, and this has been attributed to their high content of glucosinolate degradation products such as isothiocyanates (ITCs). These compounds act as anticarcinogens by inducing phase II conjugating enzymes, in particular glutathione S-transferases (GSTs). These enzymes also metabolize ITCs, such that the protective effect of cruciferous vegetables may predicate on GST genotype. The Singapore Chinese Health Study is a prospective investigation among 63 257 middle-aged men and women, who were enrolled between April 1993 and December 1998. In this nested case-control analysis, we compared 213 incident cases of colorectal cancer with 1194 controls. Information on dietary ITC intake from cruciferous vegetables, collected at recruitment via a semi-quantitative food frequency questionnaire, was combined with GSTM1, T1 and P1 genotype from peripheral blood lymphocytes or buccal mucosa. When categorized into high (greater than median) and low (less than/equal to median) intake, dietary ITC was slightly lower in cases than controls but the difference was not significant [odds ratio (OR) 0.81, 95% confidence interval (CI) 0.59-1.12]. There were no overall associations between GSTM1, T1 or P1 genotypes and colorectal cancer risk. However, among individuals with both GSTM1 and T1 null genotypes, we observed a 57% reduction in risk among high versus low consumers of ITC (OR 0.43, 95% CI 0.20-0.96), in particular for colon cancer (OR 0.31, 0.12-0.84). Our results are compatible with the hypothesis that ITCs from cruciferous vegetables modify risk of colorectal cancer in individuals with low GST activity. Further, this gene-diet interaction may be important in studies evaluating the effect of risk-enhancing compounds in the colorectum.

Case-Control Studies↗

PubMed1999

Genes, variation of cholesterol and fat intake and serum lipids.

Several studies have examined gene-diet interactions in the response of plasma lipid concentrations to changes in dietary fat and/or cholesterol. Among the gene loci examined, APOE has been the most studied, and the current evidence suggests that this locus might be responsible for some of the interindividual variability in dietary response. Other loci, including APOA4, APOA1 and APOB have also been found to account for some of the variability in the fasting and fed states.

Apolipoproteins↗

PubMed1996

Population distributions of APOE, APOH, and APOA4 polymorphisms and their relationships with quantitative plasma lipid levels among the Evenki herders of Siberia.

We examined the distributions of seven polymorphic sites in three apolipoprotein genes (APOE, APOA4, and APOH) and their relationships with quantitative lipid levels (total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides) among the Evenki reindeer herders of central Siberia. The polymorphism data reveal several distinctive features that differentiate the Evenki from white populations: the near absence of the APOE*2 allele, the highest ever recorded frequency of the APOH*3 allele, the complete absence of the APOA*2 allele at codon 360, and significantly different frequencies at three other APOA4 polymorphic sites. Our analyses of the relationships of common apolipoprotein polymorphism and plasma lipid levels also revealed interesting results. The well-established positive association between the APOE*4 allele and LDL cholesterol level reported in white populations was not seen in the Evenki despite a comparable frequency of the APOE*4 allele. Because the Evenki have significantly lower cholesterol levels than Westernized whites, this difference in allelic effect probably reflects gene-diet interaction, which modulates the effect of APOE polymorphism on LDL cholesterol. At the APOA4 locus the HincII polymorphism at codon 127 shows a significant impact on plasma triglyceride variation in the Evenki sample: The HincII - allele was associated with higher triglyceride levels than the HincII + allele. Our data indicate that both the genetic and the environmental factors conventionally associated with cardiovascular disease risk in Western societies are different in the Evenki.

Alleles↗