Biomedical subjects

Jose M Ordovas

Publications and source records attributed to Jose M Ordovas.

At least 19 recordsLinked to original sources

PubMed2006

Dietary intake of n-6 fatty acids modulates effect of apolipoprotein A5 gene on plasma fasting triglycerides, remnant lipoprotein concentrations, and lipoprotein particle size: the Framingham Heart Study.

BACKGROUND: Apolipoprotein A5 gene (APOA5) variation is associated with plasma triglycerides (TGs). However, little is known about whether dietary fat modulates this association. METHODS AND RESULTS: We investigated the interaction between APOA5 gene variation and dietary fat in determining plasma fasting TGs, remnant-like particle (RLP) concentrations, and lipoprotein particle size in 1001 men and 1147 women who were Framingham Heart Study participants. Polymorphisms -1131T>C and 56C>G, representing 2 independent haplotypes, were analyzed. Significant gene-diet interactions between the -1131T>C polymorphism and polyunsaturated fatty acid (PUFA) intake were found (P<0.001) in determining fasting TGs, RLP concentrations, and particle size, but these interactions were not found for the 56C>G polymorphism. The -1131C allele was associated with higher fasting TGs and RLP concentrations (P<0.01) in only the subjects consuming a high-PUFA diet (>6% of total energy). No heterogeneity by sex was found. These interactions showed a dose-response effect when PUFA intake was considered as a continuous variable (P<0.01). Similar interactions were found for the sizes of VLDL and LDL particles. Only in carriers of the -1131C allele did the size of these particles increase (VLDL) or decrease (LDL) as PUFA intake increased (P<0.01). We further analyzed the effects of n-6 and n-3 fatty acids and found that the PUFA-APOA5 interactions were specific for dietary n-6 fatty acids. CONCLUSIONS: Higher n-6 (but not n-3) PUFA intake increased fasting TGs, RLP concentrations, and VLDL size and decreased LDL size in APOA5 -1131C carriers, suggesting that n-6 PUFA-rich diets are related to a more atherogenic lipid profile in these subjects.

Adult↗

PubMed2006

Variants at the APOA5 locus, association with carotid atherosclerosis, and modification by obesity: the Framingham Study.

Genetic variation at the apolipoprotein A5 gene (APOA5) is associated with increased triglyceride concentrations, a risk factor for atherosclerosis. Carotid intimal medial thickness (IMT) is a surrogate measure of atherosclerosis burden. We sought to determine the association of common APOA5 genetic variants with carotid IMT and stenosis. A total of 2,273 Framingham Offspring Study participants underwent carotid ultrasound and had data on at least one of the five APOA5 variants (-1131T>C, -3A>G, 56C>G, IVS3+476G >A, and 1259T>C). Although none of the individual variants was significantly associated with carotid measures, the haplotype defined by the presence of the rare allele of the 56C>G variant was associated with a higher common carotid artery (CCA) IMT compared with the wild-type haplotype (0.75 vs. 0.73 mm; P < 0.05). The rare allele of each of the -1131T >C, -3A>G, IVS3+476G>A, and 1259T>C variants and the haplotype defined by the presence of the rare alleles in these four variants were each significantly associated with CCA IMT in obese participants. These associations remained significant even after adjustment for triglycerides. APOA5 variants were associated with CCA IMT, particularly in obese participants. The mechanism of these associations and the effect modification by obesity are independent of fasting triglyceride levels.

Apolipoprotein A-V↗

PubMed2006

Association between well-characterized lipoprotein-related genetic variants and carotid intimal medial thickness and stenosis: The Framingham Heart Study.

OBJECTIVE: To determine the association of well-characterized lipoprotein-related genetic variants with carotid intimal medial thickness (IMT) and stenosis. METHODS: 3380 men and women from the Framingham Offspring Study underwent carotid ultrasound to determine carotid IMT and stenosis>/=25%. We genotyped 12 variants in 10 lipoprotein-related genes known to be associated with significant differences in lipoprotein levels. RESULTS: For most of the variants, there was no association with carotid IMT. In multivariable, sex-specific analyses, the rare allele of the cholesterol ester transfer protein (CETP) TaqIB variant was associated with lower ICA IMT in men. Hypertension was associated with higher ICA IMT only in male carriers of the rare allele of the APOCIII Sst-1 variant (p for the interaction=0.041). In analyses of carotid stenosis in male, carriers of the lipoprotein lipase (LPL) N291S rare variant showed a higher risk of carotid stenosis (OR=2.59, 95% confidence interval: 1.11-6.02, p=0.028) compared to NN genotype. CONCLUSIONS: While there is no evidence for a significant association of several common lipoprotein-related genetic variants with carotid IMT, our results are consistent with the previously reported role of CETP and LPL genetic variants in cardiovascular risk and the possible modulation of the association between hypertension and carotid IMT by APOCIII Sst-1 variant.

Adolescent↗

PubMed2006

The Nutrition, Aging, and Memory in Elders (NAME) study: design and methods for a study of micronutrients and cognitive function in a homebound elderly population.

BACKGROUND: Micronutrient status can affect cognitive function in the elderly; however, there is much to learn about the precise effects. Understanding mediating factors by which micronutrient status affects cognitive function would contribute to elders' quality of life and their ability to remain in the home. OBJECTIVES: The Nutrition, Aging, and Memory in Elders (NAME) Study is designed to advance the current level of knowledge by investigating potential mediating factors by which micronutrient status contributes to cognitive impairment and central nervous system abnormalities in the elderly. NAME targets homebound elders because they are understudied and particularly at risk for poor nutritional status. METHODS: Subjects are community-based elders aged 60 and older, recruited through area Aging Services Access Points. The NAME core data include demographics; neuropsychological testing and activities of daily living measures; food frequency, health and behavioral questionnaires; anthropometrics; gene status; plasma micronutrients, homocysteine, and other blood determinants. A neurological examination, psychiatric examination, and brain MRI and volumetric measurements are obtained from a sub-sample. RESULTS: Preliminary data from first 300 subjects are reported. These data show that the NAME protocol is feasible and that the enrolled subjects are racially diverse, at-risk, and had similar basic demographics to the population from which they were drawn. CONCLUSION: The goal of the NAME study is to evaluate novel relationships between nutritional factors and cognitive impairment. These data may provide important information on potential new therapeutic strategies and supplementation standards for the elderly to maintain cognitive function and potentially reduce the public health costs of dementia.

Activities of Daily Living↗

PubMed2006

The SNP276G>T polymorphism in the adiponectin (ACDC) gene is more strongly associated with insulin resistance and cardiovascular disease risk than SNP45T>G in nonobese/nondiabetic Korean men independent of abdominal adiposity and circulating plasma adiponectin.

This study aimed to determine whether polymorphisms of the adiponectin (ACDC) gene independently contribute to insulin resistance (IR) and other cardiovascular disease (CVD) risk factors in nonobese, nondiabetic Korean men after adjusting for major environmental factors that influence IR. Among the 7 ACDC single-nucleotide polymorphisms (SNPs;C-11377G, T45G, G276T, H241P, Y111H, G90S, and R221S) prescreened in 48 subjects, we genotyped 333 subjects for SNP45 and SNP276, both of which showed an allele frequency of more than 2%. In Pearson correlation and multiple stepwise regression analyses, we found that waist circumference was the most important influencing factor (beta = .369, P < .001) in homeostasis model assessment (HOMA)-IR, whereas plasma adiponectin was the second most important (beta = -.217, P = .023). At position 276, T/T subjects showed significantly lower glucose concentrations (P = .043) and higher low-density lipoprotein particle sizes (P = .033) than the G/G and G/T subjects. The subjects also had lower serum triglycerides and HOMA-IR; however, these results were not statistically significant. After adjusting for waist circumference and plasma adiponectin, T/T subjects showed a significantly lower HOMA-IR than G/G or G/T subjects (P = .048). On the other hand, at position 45, only glucose concentrations were significantly lower in G carriers (P = .005). In the SNP45-SNP276 haplotype test, TT/TT subjects (having T/T at both SNP45 and SNP276) showed significantly lower IR before and after adjusting for waist circumference and adiponectin levels than did other carriers. In conclusion, we suggest that SNP276G>T, rather than SNP45T>G, is more strongly associated (both directly and indirectly) than with several components of metabolic syndrome and CVD risk, including IR, triglyceride concentration, and low-density lipoprotein particle size, in nonobese, nondiabetic men.

Abdomen↗

PubMed2006

The ABCG5 polymorphism contributes to individual responses to dietary cholesterol and carotenoids in eggs.

The ATP binding cassette G5 (ABCG5) polymorphisms have been postulated to play a role in the response to dietary cholesterol. The objective of this study was to examine the contribution of the ABCG5 polymorphism on the plasma response to consumption of cholesterol and carotenoids from eggs. For this purpose, genotyping was conducted for 40 men and 51 premenopausal women who were randomly assigned to consume an egg (EGG, 640 mg/d additional dietary cholesterol and 600 microg lutein+ zeaxanthin) or placebo (SUB, 0 mg/d cholesterol, 0 microg lutein + zeaxanthin) diet for 30 d. The two arms of the dietary intervention were separated by a 3-wk washout period. Plasma concentrations of total cholesterol, LDL cholesterol (LDL-C), and HDL cholesterol were determined. Because eggs are an excellent source of lutein and zeaxanthin, the plasma levels of these carotenoids were also measured in a subset of subjects to determine whether the response to carotenoid intake was similar to that seen for dietary cholesterol and to evaluate the contribution of ABCG5 polymorphism to both responses. Individuals possessing the C/C genotype experienced a greater increase in both LDL-C (P < 0.05) and a trend for lutein (P = 0.08) during the EGG period compared with those individuals with the C/G (heterozygote) or G/G genotypes (homozygotes). These results, although obtained from a small number of subjects, suggest that the ABCG5 polymorphism may play a role in the plasma response to dietary cholesterol and carotenoids.

ATP Binding Cassette Transporter, Subfamily G, Mem↗

PubMed2006

Metagenomics: the role of the microbiome in cardiovascular diseases.

PURPOSE OF REVIEW: The human oral and intestinal microbiota interact with the host through poorly understood metabolic pathways. Investigation of such complex ecosystems and interactions has been difficult. In this paper, we assess the current evidence supporting the role of the microbiota as a significant determinant of cardiovascular disease risk. RECENT FINDINGS: The link between oral disease and cardiovascular disease was established about 15 years ago. The accumulated evidence supports, but does not prove a causal association between periodontal infection and cardiovascular disease and suggests some physiologically obvious connections between these pathologies, namely, inflammatory and immune responses, and hemostasis. Moreover, some studies have observed higher concentrations of total and LDL-cholesterol and triglycerides and lower concentrations of HDL-cholesterol in individuals with periodontitis before periodontal treatment. Likewise, recent reports suggest the influence of the gut microbiome in the risk of common age-related diseases such as cancer and potentially cardiovascular disease through modification of classical risk factors such as obesity, insulin resistance and plasma lipids. SUMMARY: The recognition that microorganisms may play an even more important role in maintaining human health than in generating diseases places metagenomics as one of the most relevant areas of future research. The knowledge of the hundreds of genomes that we host and their interaction with our own genome shall provide a much more complete understanding of the individual nutritional needs and may be an obligated part of future personalized healthcare approaches.

Cardiovascular Diseases↗

PubMed2006

Angiotensin-converting enzyme genotype and adherence to aerobic exercise training.

Angiotensin-converting enzyme (ACE) has two common genetic variants: the insertion (I) and deletion (D) forms. ACE levels are greater in subjects with the D allele, and several studies suggest superior endurance performance in subjects with the I allele. The authors recently reported the results of a 6-month exercise training protocol examining the effect of apolipoprotein E on the lipid response. The present report examines the relationship of ACE genotype and exercise adherence. DNA samples were available for 110 subjects: 14 I/I, 52 I/D, and 44 D/D. Baseline and change in maximal oxygen uptake, body mass index, skinfold thickness, and serum lipids did not differ by ACE genotype, but adherence to exercise training was higher in I carriers than in D homozygotes. These preliminary results suggest that ACE genotype affects exercise adherence and raises the possibility that superior endurance capacity in subjects with the I allele is related to a genetic propensity to adhere to an exercise regimen.

Adolescent↗

PubMed2005

The L162V polymorphism at the peroxisome proliferator activated receptor alpha locus modulates the risk of cardiovascular events associated with insulin resistance and diabetes mellitus: the Veterans Affairs HDL Intervention Trial (VA-HIT).

BACKGROUND: The Veterans Affairs HDL Intervention Trial (VA-HIT) showed that gemfibrozil, which activates peroxisome proliferator-activator receptor alpha (PPARalpha), significantly reduced the risk of cardiovascular (CV) events in men with low HDL cholesterol (< 40 mg/dl) and established coronary heart disease. Treatment was particularly beneficial in those with insulin resistance (IR) or diabetes mellitus (DM). We hypothesized that the association between a functional polymorphism at the PPARA locus (L162V) and the risk of a CV event, as well as response to fibrate therapy, might be greatest in those with either IR or DM (DM/IR) in VA-HIT. METHODS AND RESULTS: A total of 827 men (placebo, n = 413; gemfibrozil, n = 414) from the VA-HIT were genotyped. This population included a high proportion of subjects with DM/IR. In VA-HIT, the PPARA V162 allele was associated with reduced levels of HDL cholesterol and the presence of DM/IR at baseline. It was also associated with reduced risk of CV events in those with DM/IR but not in those with neither (DM/IR *PPARA genotype, P = 0.005). Among subjects with DM/IR, treatment with gemfibrozil reduced CV events in non-carriers from 29.9 to 17.8% and carriers of the V162 allele from 14.7 to 4.8%. In contrast, carriers of the V162 allele with no DM/IR who were treated with gemfibrozil experienced significantly more CV events than did those who received placebo (20.6% versus 13.6%; P = 0.01). CONCLUSIONS: The effect of the L162V polymorphism at the PPARA locus on CV risk depends on the presence of DM/IR. Among subjects treated with gemfibrozil, the V162 allele was associated not only with reduced CV risk in subjects with DM/IR, but also with significantly increased CV risk in the absence of these traits, identifying this genetic variant as a potential marker for predicting which subjects may have a favorable response to fibrate therapy.

Alleles↗

PubMed2005

Tobacco smoking, estrogen receptor alpha gene variation and small low density lipoprotein level.

High levels of small low density lipoprotein (LDL) particles are a major risk factor for cardiovascular morbidity and mortality. Both estrogens and smoking, with known anti-estrogenic effects, alter the atherogenic lipid profile. We tested for a role of interaction between smoking and estrogen receptor alpha gene (ESR1) variation in association with plasma concentration of atherogenic small LDL particles and LDL particle size. We studied 1727 unrelated subjects, 854 women and 873 men, mean age 51 years (SD 10), from the population-based Framingham Heart Study. After covariate adjustment, women who smoked and had the common ESR1 c.454-397 TT genotype (in 30% of women, T was present on both chromosomes at position 397 prior to the start of exon 2) had >1.7-fold higher levels of small LDL particles than women with the alternative genotypes (P-value for smoking-genotype interaction was 0.001). Similar results were obtained for three other ESR1 variants including c.454-351A > G, in the same linkage disequilibrium block. A similar substantial gender-specific result was also evident with a fifth variant, in a separate linkage disequilibrium block, in exon 4 (P = 0.003). Women who smoked and had specific, common ESR1 genotypes had a substantially higher plasma concentration of atherogenic small LDL particles. Significant results revealed a dose-dependent effect of smoking and were evident in both pre- and postmenopausal women. The reported association has the potential to explain the risks associated with estrogen use in certain women and a recent report of association between an ESR1 haplotype comprised of c.454-397 T and c.454-351 A alleles with increased myocardial infarction and ischaemic heart disease, independent of the standard, established cardiovascular risk factors.

Estrogen Receptor alpha↗

PubMed2005

Estrogen receptor-alpha variants are associated with lipoprotein size distribution and particle levels in women: the Framingham Heart Study.

Plasma lipid profile is affected by endogenous estrogen levels and hormone replacement therapy (HRT). As plasma lipid concentrations have a significant heritable basis and the effects of both endogenous estrogen and use of HRT are mediated by estrogen receptors, we sought to investigate the relationships between polymorphisms in estrogen receptor-alpha (ESR1) and plasma lipid and lipoprotein concentrations. We analyzed data from 854 women (mean age 52+/-10 years) from the Framingham Heart Study. A TA repeat in the promoter region, c.30T>C in exon 1, c.454-397T>C, and c.454-351A>G in intron 1, all in linkage disequilibrium (LD), were significantly associated with low-density lipoprotein (LDL) particle size and concentration of small LDL particles. Women with the c.454-397C allele had larger LDL particle size (21.09+/-0.02 nm versus 21.01+/-0.03 nm, p=0.021) concurrent with lower small LDL particle concentration (0.47+/-0.02 mmol/L versus 0.58+/-0.03 mmol/L, p=0.008). Moreover, the TA[L]-c.30C-c.454-397C-c.454-351G haplotype (frequency, 32%) was associated with lower small LDL particle concentrations (-0.06+/-0.03 mmol/L change associated with each copy of this haplotype, p=0.011) when compared to the TA[S]-c.30T-c.454-397T-c.454-351A haplotype (frequency, 46%), where L and S are long and short TA repeats. Our results suggest that common ESR1 polymorphisms have a significant effect on lipoprotein metabolism in women.

Alleles↗

PubMed2005

Associations between plasma lipid parameters and APOC3 and APOA4 genotypes in a healthy population are independent of dietary cholesterol intake.

To determine whether APOC3 and APOA4 genotypes influence plasma cholesterol fluctuations following a high cholesterol diet, a healthy population of 40 men and 51 women were studied. The crossover intervention randomly assigned participants to an EGG (640 mg/d cholesterol) or placebo (0 mg/d cholesterol) diet for 30 days, with a 3-week washout between periods. Allele-specific oligonucleotide hybridization was utilized to determine the presence or absence of APOC3 and APOA4 polymorphisms. Differences in plasma cholesterol between hyper- and hypo-responders were not influenced by genotype. However, an interaction (P < 0.0001) did exist between APOA4 allele, diet and gender with regard to triglycerides (TG). While female carriers of the APOA4(347) S allele had lower TG concentrations than those with the common T/T allele, males with the S allele had higher concentrations. The APOC3 SstI polymorphism analysis revealed that heterozygous carriers of the S2 allele had higher (P < 0.05) plasma apo C-III and TG concentrations, regardless of gender or dietary period. In addition, carriers of the S2 allele had smaller LDL peak particle diameter than those having the common APOC3 genotype. The presence of individual alleles in this population was associated with differences in plasma lipids and LDL size. However, these relationships were independent of dietary cholesterol.

Adult↗

PubMed2005

Genome-wide linkage analyses and candidate gene fine mapping for HDL3 cholesterol: the Framingham Study.

High density lipoprotein cholesterol (HDL-C) is inversely associated with coronary heart disease and has a genetic component; however, linkage to HDL-C is not conclusive. Subfractions of HDL, such as HDL(3)-C, may be better phenotypes for linkage studies. Using HDL(3)-C levels measured on 907 Framingham Heart Study subjects from 330 families around 1987, we conducted a genome-wide variance components linkage analysis with 401 microsatellite markers spaced approximately 10 centimorgan (cM) apart. Nine candidate genes were identified and annotated using a bioinformatics approach in the region of the highest linkage peak. Twenty-eight single nucleotide polymorphisms (SNPs) were selected from these candidate genes, and linkage and family-based association fine mapping were conducted using these SNPs. The highest multipoint log-of-the-odds (LOD) score from the initial linkage analysis was 3.7 at 133 cM on chromosome 6. Linkage analyses with additional SNPs yielded the highest LOD score of 4.0 at 129 cM on chromosome 6. Family-based association analysis revealed that SNP rs2257104 in PLAGL1 at approximately 143 cM was associated with multivariable adjusted HDL(3) (P = 0.03). Further study of the linkage region and exploration of other variants in PLAGL1 are warranted to define the potential functional variants of HDL-C metabolism.

Adult↗

PubMed2005

Intragenic linkage disequilibrium structure of the human perilipin gene (PLIN) and haplotype association with increased obesity risk in a multiethnic Asian population.

Perilipin is a lipid droplet surface protein present in adipocytes and steroidogenic cells. We examined five common single nucleotide polymorphisms (SNPs) at the perilipin (PLIN) locus (PLIN 6209C>T, 10171A>T, 11482G>A, 13041A>G, and 14995A>T) to investigate their association with obesity risk. The study population included 4,131 subjects of three ethnic groups (Chinese, Malay, and Indian) from Singapore. The prevalence of obesity in Malays and Indians was much higher than in Chinese. Moreover, in these groups the prevalence of obesity was three times higher in women than in men. Crude analysis indicated that haplotype 11212 (CAAAT) is shared by Malays and Indians and is significantly associated with increased obesity risk as compared to the most common haplotype 21111 (TAGAA): OR 1.65 (95% CI 1.11-2.46) in Malays and 1.94 (95% CI 1.06-3.53) in Indians. No associations between PLIN haplotypes and obesity risk were found in Chinese. To simplify the haplotype analyses we used a subgroup of three SNPs (11482G>A, 13041A>G, and 14995A>T) in positive linkage disequilibrium. These analyses revealed similar associations, showing that haplotypes XX212 (XXAAT) and XX222 (XXAGT) are associated with increased obesity risk in Malays OR 2.04 (95% CI 1.28-3.25) and 2.05 (95% CI 1.35-3.12) respectively, and that haplotype XXX212 (XXAAT) is significantly associated with increased obesity risk in Indians OR 2.16 (95% CI 1.10-4.26) after adjusting for covariates including age, sex, smoking, alcohol consumption, exercise, and diabetes status. Moreover, individual SNP analyses demonstrated that the PLIN 14995A>T SNP is the most informative single genetic marker for the observed haplotype association, being significantly associated with increased obesity risk in both Malays OR 2.28 (95% CI 1.45-3.57) and Indians OR 2.04 (95% CI 1.08-3.64). These results support the role of the PLIN locus as an ethnically dependent modulator of obesity risk in humans.

Adolescent↗

PubMed2005

Genetic variation and lipid metabolism: modulation by dietary factors.

Cardiovascular diseases (CVD) result from complex interactions between genetic and environmental factors. The evidence supports that gene-environment interactions modulate plasma lipid concentrations and potentially CVD risk. The findings from studies examining gene-diet interactions and lipid metabolism have been promising. Several loci (eg, APOA1, APOE, LIPC) are providing proof of concept for the application of genetics in the context of personalized nutrition for CVD prevention. The spectrum of candidate genes has been expanding to incorporate those involved in intracellular lipid metabolism (eg, iPPARs, CYP7A1). However, the practical application of these findings is not ready for prime time. There is a compelling need for replication using a higher level of scientific evidence. Moreover, we need to evolve from the simple scenarios examined nowadays (ie, one single dietary component, SNP, and risk factor) to more realistic situations involving multiple interactions. In summary, there is need for both large population studies and well-standardized intervention studies.

Cardiovascular Diseases↗

PubMed2005

Gender-specific effects of estrogen receptor alpha gene haplotype on high-density lipoprotein cholesterol response to atorvastatin: interaction with apolipoprotein AI gene polymorphism.

Statins can modestly raise the levels of HDL cholesterol and apolipoprotein A-I (APOA1). Recently, associations between polymorphisms in the estrogen receptor alpha (ESR1) and the HDL cholesterol response to hormone replacement therapy were reported. To test the hypothesis that common polymorphisms in ESR1 and APOA1 genes are associated with the response to statin therapy, two ESR1 (PvuII and XbaI) and two APOA1 (G-75A and +83) polymorphisms were examined in 338 hypercholesterolemic patients treated with atorvastatin 10mg. The ESR1 PvuII-XbaI+ haplotype was significantly, and independently, associated with a greater response of HDL raising in women (+13% versus +7%, p=0.010) but not in men (+9% versus +7%, p=0.248). Effects of the APOA1+83 variant allele on HDL cholesterol response also differed significantly by gender (p=0.012). The APOA1+83 variant allele was associated with higher basal LDL cholesterol levels in men as well, but not in women. Finally, significant interactions were observed between the ESR1 PvuII-XbaI+ haplotype and the APOA1+83 variant allele regarding both HDL (p=0.042) and LDL (p=0.031) cholesterol responses. In conclusion, the ESR1 haplotype was associated with a greater HDL-raising to atorvastatin in a gender-specific manner, and the interactions between ESR1 and APOA1 genotypes regarding HDL and LDL cholesterol response were also gender specific.

Aged↗

PubMed2005

A promoter polymorphism in cholesterol 7alpha-hydroxylase interacts with apolipoprotein E genotype in the LDL-lowering response to atorvastatin.

Bile-acid biosynthesis is a key determinant of intracellular cholesterol and, in turn, cholesterol synthesis rate in hepatocytes. This suggests that variation in the cholesterol 7alpha-hydroxylase gene (CYP7A1), a key enzyme in bile-acid biosynthesis, may influence the statin response. To test this hypothesis, a promoter polymorphism (A-204C) in CYP7A1 was examined in 324 hypercholesterolemic patients treated with atorvastatin 10mg. The variant C allele was significantly and independently associated with poor LDL cholesterol reductions; -39% in wild type allele homozygotes, -37% in variant allele heterozygotes, and -34% in variant allele homozygotes (p<0.0001 for trend). Differences were more striking in men, and were enhanced by the coexistence of common variants of apolipoprotein E gene (APOE), epsilon2 or epsilon4. In subjects having wild type alleles at both loci, the mean reduction in LDL cholesterol was -40%, while the value in subjects having two CYP7A1 variant alleles and at least one variant APOE allele was -31% (p<0.0001). Combination analysis of these two loci more accurately predicted the achievement of goal LDL cholesterol, than did both single locus analysis. We concluded that the CYP7A1 A-204C promoter variant was associated with poor response to atorvastatin, which were additively enhanced by common variants in another locus, APOE.

Aged↗

PubMed2005

Effect of influenza vaccine on markers of inflammation and lipid profile.

Despite wide use of the influenza vaccine, relatively little is known about its effect on the measurement of inflammatory markers. Because inflammatory markers such as C-reactive protein (CRP) are increasingly being used in conjunction with lipids for the clinical assessment of cardiovascular disease and in epidemiologic studies, we evaluated the effect of influenza vaccination on markers of inflammation and plasma lipid concentrations. We drew blood from 22 healthy individuals 1 to 6 hours before they were given an influenza vaccination and 1, 3, and 7 days after the vaccination. Plasma CRP, interleukin (IL)-6, monocyte chemotactic protein 1, tumor necrosis factor alpha, IL-2 soluble receptor alpha, and serum amyloid A were measured, and differences in mean concentrations of absolute and normalized values on days 1, 3, and 7 were compared with mean baseline values. There was a significant increase in mean IL-6 (P < .01 absolute values, P < .001 normalized values) on day 1 after receiving the influenza vaccine. The mean increases in normalized high sensitivity CRP values were significant on day 1 (P < .01) and day 3 (P = .05), whereas the mean increase in normalized serum amyloid A was significant only on day 1 (P < .05). No significant changes were seen in mean concentrations of IL-2 soluble receptor alpha, monocyte chemotactic protein-1, or tumor necrosis factor-alpha. Of the lipids, significant decreases in mean concentrations of normalized triglyceride values were seen on days 1 (P < .05), 3 (P < .001), and 7 (P < .05) after vaccination. Our findings show that the influenza vaccination causes transient changes in select markers of inflammation and lipids. Consequently, clinical and epidemiologic interpretation of the biomarkers affected should take into account the possible effects of influenza vaccination.

Adult↗