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Biomedical subjects

S E Humphries

Publications and source records attributed to S E Humphries.

At least 19 recordsLinked to original sources
PubMed2007

Interleukin-18 genetics and inflammatory disease susceptibility.

IL18 was mapped to 11q22.2-22.3 in 1998. Owing to interleukin (IL)-18's important and novel role in immunomodulation, the gene itself has been subject to scrutiny, with the aim of discovering variants that may impact on disease susceptibility and/or progression. Despite being sequenced numerous times in different populations, no non-synonymous variants have been found. However, a number of polymorphisms within the proximal promoter have been verified that may interfere with transcription-factor-binding sites. Much of the subsequent association analyses have centred on these variants, but have yielded no consistent results, despite numerous different study populations being genotyped. IL18 has recently been resequenced in its entirety, enabling the tagging-single-nucleotide polymorphism (tSNP) methodology to be adopted. This approach has yielded interesting results, with genetic variation being shown to affect protein levels, and risk. This review aims to compile and reflect on the association data of interest published to date, with a focus on the diseases related to aberrant inflammatory control.

Arthritis↗
PubMed2007

Common adiponectin gene variants show different effects on risk of cardiovascular disease and type 2 diabetes in European subjects.

Alterations in the secretion of adipokines may explain the link between obesity, type 2 diabetes (T2DM) and coronary artery disease (CAD). These conditions have been associated with variation in the adiponectin gene, although evidence for this relationship has been variable, with differences found even in similar samples. This study aims to clarify these inconsistencies by determining the impact of identified adiponectin gene (ADIPOQ) variants (-11391G>A,-1377C>G[promoter] and +45T>G[exon 2] and +276G>T[intron 2]) on the prospective risk of CAD and T2DM in healthy men, and on adverse metabolic markers, in myocardial infarct survivors and controls from different parts of Europe. The hazard ratio for cardiovascular disease varied across the -11391GG/GA/AA(p = 0.03) and -11371CC/CG/GG(p = 0.05) genotypes only. In contrast, only the +45T>G variant (3.80[1.76-8.24]) was associated with T2DM, while two haplotypes GCTT/GCGG (p < 0.05) and +276G>T(p = 0.01) increased risk in interaction with obesity. The variants were associated with a number of biomarkers in Southern but not Northern Europe (p = 0.01), despite no significant differences in allele or haplotype frequencies (p > 0.44). A risk haplotype could not be identified in either sample. Adiponectin gene variants are hence currently poor markers for the development of T2DM and CAD. Their influence on risk depends significantly on interactions that are not currently understood with either genetic variation elsewhere or the environment of the sample studied.

Adiponectin↗
PubMed2007

The impact of ACE genotype on serum ACE activity in a black South African male population.

The strong association between the angiotensin I-converting enzyme (ACE) gene I/D polymorphism with serum ACE activity appears lacking in Nigerians and Kenyans, but has not previously been well assessed in others of African origin. This study addressed this issue in an ethnically well defined black South African population. A putative association for the A22982G ACE gene variant, a QTL likely to impact on serum ACE activity, was also sought. Subjects were 200 healthy male black South African volunteers from the Xhosa ethnic group. Venous blood was obtained from all subjects for DNA extraction. ACE I/D and A22982G genotypes were determined and serum ACE activity measured. Age and blood pressure were recorded. For the group as a whole (mean +/- SD age 38.5 +/- 9.8 years, SBP 119.6 +/- 14.1 mmHg, DBP 78.2 +/- 10.1 mmHg) serum ACE activity was 38.2 +/- 11.2 nmol ml(-1)min(-1). ACE I/D genotype was not significantly associated with serum ACE activity. In contrast, the A22982G variant was significantly associated with serum ACE activity, being 35.9 +/- 9.6, 38.1 +/- 10.6 and 42.4 +/- 15.3 nmol ml(-1)min(-1) for AA, AG and GG genotypes respectively; p = 0.03 by ANOVA and p = 0.01 by linear trend. In keeping with the findings in some other African populations, the ACE I/D polymorphism is not strongly associated with serum ACE activity in Xhosa South Africans. As such, it cannot be used as a marker of ACE activity in these subjects. In this regard the use of the A22982G gene variant may be more appropriate.

Black People↗
PubMed2006

Polymorphisms in the angiotensin converting enzyme gene and growth in the first year of life.

Abnormal patterns of fetal and infant growth have been associated with an increased risk of cardiovascular disease in adulthood. Catch-up growth during the first year of life has been associated with a higher prevalence of type 2 diabetes mellitus, whereas a lack of catch-up growth tracks with a risk of hypertension. The role of genetic factors influencing both growth and blood pressure have not been explored. We genotyped cord blood samples from 530 singleton, Caucasian, uncomplicated pregnancies, drawn from a larger cohort of 1650 pregnancies, and related polymorphism in the angiotensin converting enzyme (ACE) gene (alleles insertion (I) or deletion (D)) with measures of size at birth and at age of 1 year. ACE genotype did not significantly influence size at birth, although there was a greater proportion of individuals with the D/D genotype born with a birth weight less than the 10th centile (P=0.004). The ACE I/I genotype was significantly associated with higher weight (p=0.001), body mass index (p=0.001) and mid arm circumference (p=0.001) at 1 year of age compared to the ACE D/D and I/D genotypes. Individuals with the I/I genotype displayed catch-up (gain from birth size of >or=0.6 Standard Deviation Score) in weight (p=0.04), body mass index (p=0.03) and mid arm circumference (p=0.03) compared to the D/D group, the majority of which showed no change or catch-down. The I/D genotype was distributed equally across the catch up/catch down/no change categories. The effect was more marked in males, but ACE genotype and sex of the infant contributed independently to mid arm circumference measurements and there was no interaction between the two. There was no effect of maternal or paternal ACE genotype on birth size. In a multiple linear regression model ACE genotype, socioeconomic status and sex of the infant explained 10.9% of the variance in body mass index SDS at 1 year of age. We conclude that the ACE I/I genotype is associated with a higher weight and body mass index SDS at 1 year of age, along with catch-up in terms of these measures from birth to 1 year. The D/D genotype is associated with a greater proportion of babies, born at term, that at small for gestational age. These results suggest that due consideration should be given to the underlying genotype of an individual when evaluating the association of early human growth with the development of risk factors for cardiovascular disease. The observation of independent effects of genotype, sex of the individual and socioeconomic status on postnatal growth suggests the need to develop methodologies for the integration of genetic and environmental factors in causality modelling.

Adult↗
PubMed2006

Increase of plasma fibrinogen levels and variability with age in a sample of middle aged healthy men.

According to predictions from the current theoretical models for ageing the heterogeneity of the population is increasing with increasing age. Although the direct observation of such changes in humans is extremely difficult, supporting evidence should be identifiable in key biomarkers associated with health and mortality. Using data from the Northwick Park Heart Study II of 3052 healthy middle-aged men (mean 56 years of age, range 49-69 years), with 5 annual measures of CHD risk factors, ageing effects were tested for plasma fibrinogen, cholesterol and triglycerides. Fibrinogen levels increased with age (p < 0.0001), while cholesterol showed a decrease, and triglycerides did not show any change with age. There was a significant increase in the variance of fibrinogen with age (p < 0.0007) but not for cholesterol or triglycerides. The raising effect on fibrinogen levels associated with the A allele of the FIBB - 455G>A promoter variant also decreased with age (p = 0.005). The age-associated changes observed in the fibrinogen variability and the association of phenotype to genotype are discussed in light of the evolutionary theory, and their implications are considered.

Aged↗
PubMed2006

The apolipoprotein A-V genotype and plasma apolipoprotein A-V and triglyceride levels: prospective risk of type 2 diabetes. Results from the Northwick Park Heart Study II.

AIMS/HYPOTHESIS: We sought to establish the relationship between plasma apolipoprotein A-V (APOA5, previously known as apoA-V) and triglyceride levels and to determine the impact of the APOA5 genotype on APOA5 levels and development of type 2 diabetes in a 15-year follow-up study of healthy UK men. MATERIALS AND METHODS: APOA5 -1131T>C and S19W genotypes were determined in 2,490 men, of whom 145 subsequently developed type 2 diabetes. In a subset of 299 men, we also determined APOA5 levels. RESULTS: Plasma APOA5 levels positively correlated with triglycerides (r=0.18, p<0.002) and were not different in men who subsequently developed type 2 diabetes compared with healthy men (p=0.7). Carriers of either APOA5 W19 or -1131C had, as expected, higher plasma triglycerides. However, while W19 carriers had significantly higher APOA5 levels (p=0.0003), APOA5 levels were not associated with -1131T>C (p=0.63), reinforcing the idea that the reported -1131C association with triglycerides levels is due to linkage disequilibrium with variants in the APOC3 gene, and not due to the direct effect on APOA5 levels. Overall no effect of APOA5 -1131T>C or S19W was found on type 2 diabetes risk. CONCLUSIONS/INTERPRETATION: In contrast to animal studies, in man, plasma APOA5 positively correlates with plasma triglyceride levels. In prospective analysis, with the caveat that numbers were small, APOA5 genotypes do not appear to have an impact on risk of development of type 2 diabetes.

Apolipoprotein A-V↗
PubMed2006

Cognitive outcome and cyclo-oxygenase-2 gene (-765 G/C) variation in the preterm infant.

BACKGROUND: Cyclo-oxygenase (COX) inhibition by indomethacin does not result in an improvement in long-term neurocognitive outcome, despite reducing the incidence of both severe intraventricular haemorrhage and white matter injury visible on ultrasound. Diffuse brain injury after preterm birth may have inflammatory origins. These two points suggest that, in the preterm brain, COX inhibition may have a dominant proinflammatory or neuropathological role. The inducible form of the COX2 gene is polymorphic: the -765 C (rather than G) variant of the gene is associated with reduced COX2 activity. OBJECTIVE: To test the hypothesis that the C allele of COX2 is associated with worse neurodevelopmental outcomes after premature birth. OUTCOMES: Cerebral palsy, disability, Griffith's developmental quotient at 2 years and British Ability Scales-11 general cognitive ability and motor performance (movement assessment battery for children) at 5(1/2) years were compared with COX2 genotype. RESULTS: The C allele (GC 65 (31%), CC 3 (1%)) was independently associated with worse cognitive performance at 2 and 5(1/2) years: C allele mean (SEM) developmental quotient 92.7 (1.7), v GG 97.6 (1.5), p = 0.039; C allele mean (SEM) general cognitive ability, 94.3 (2.2) v GG 100.9 (1.7), p = 0.028. CONCLUSION: An antineuropathological role for COX2 in the preterm brain may help account for the lack of effect of indomethacin treatment in improving neurocognitive outcomes in children born preterm, despite reported reduction in apparent brain injury.

Alleles↗
PubMed2006

Left ventricular growth response to exercise and cigarette smoking: data from LARGE Heart.

BACKGROUND: Increasing left ventricular mass is a risk factor for cardiovascular morbidity and mortality. OBJECTIVE: To examine the possible association of smoking with the left ventricular growth response in men. METHODS: Left ventricular mass was measured in 309 army recruits before and after an identical 12-week physical training programme. Left ventricular mass was determined using cardiovascular magnetic resonance. RESULTS: Left ventricular mass increased with training (mean (standard deviation (SD)) 3.83 (10.81) g, p<0.001). By univariate analysis, exercise-induced change in left ventricular mass was positively associated with cigarette smoking (mean (SD) 1.69 (11.10) g v 4.76 (10.23) g for non-smokers v ex- and current smokers, respectively; p = 0.026), whereas age, height, diastolic and systolic blood pressure (SBP), alcohol consumption or indices of physical activity were not significantly associated with change in left ventricular mass. Multivariate analysis showed body weight, smoking status and SBP to be independent predictors of left ventricular mass (incremental R(2) = 3.4%, p = 0.004; R(2) = 4.9%, p = 0.024; and R(2) = 1.7%, p = 0.041, respectively). CONCLUSIONS: Cigarette smoking and SBP are associated with exercise-induced left ventricular growth in young men. The positive association of smoking with changes in left ventricular mass is surprising, given the limited exposure of these subjects to smoking, and although these data do not prove causation, they are of great interest to those trying to uncover the drivers of left ventricular hypertrophy, as well as to those examining the possible ill-effects of smoking in the young.

Analysis of Variance↗
PubMed2006

The interleukin-6 gene -174G>C and -572G>C promoter polymorphisms are related to cerebral aneurysms.

BACKGROUND AND AIMS: An important part is played by inflammation in intracranial aneurysm formation. The hypothesis that there is an association of the proinflammatory cytokine interleukin-6 (IL-6) genotypes (-572G>C and -174G>C) with intracranial aneurysms was tested. METHODS: IL-6 genotypes were determined in 91 Caucasian patients with aneurysms and compared with 2720 healthy UK controls. RESULTS: For both polymorphisms, the distribution of the genotypes and estimated allele frequency were different between the control group and the aneurysm group. For -572G>C, a higher frequency of the C allele (p = 0.001) and more people homozygous for the C allele were found among those with aneurysms than among the controls (4.4% v 0.3%, p = 0.001). For -174G>C, more people homozygous for the C allele were found among the controls than among those with aneurysm (18% v 7%, p = 0.007). The 572C/174G haplotype was associated with an increased risk of aneurysms, with the relative risk compared with the common haplotype being 1.89 and that for the -572G/174C haplotype being 0.58 (p<0.0005). CONCLUSION: This is the first study to show that IL-6 promoter polymorphisms are associated with intracranial aneurysmal disease. Whether this association is with the development, progression or rupture of such aneurysms, or represents survivor bias, is unclear.

Adult↗
PubMed2006

Adiponectin and its gene variants as risk factors for insulin resistance, the metabolic syndrome and cardiovascular disease.

The increasing prevalence of obesity and metabolic syndrome/insulin resistance has attracted considerable interest due to their identification as risk factors for cardiovascular disease and, hence, targets for cardiovascular disease prevention. This review focuses on adiponectin, the most profusely secreted protein from adipose tissue, which itself is being increasingly recognised as an important and very active endocrine organ, secreting a wide range of biologically active substances known as adipokines or adipocytokines. Adiponectin has been demonstrated to have insulin sensitising effects, and secretion of adiponectin is reduced as adipose tissue mass increases. Adiponectin has also been demonstrated to have anti-inflammatory and anti-atherogenic properties, and is independently associated with cardiovascular disease. The evidence that suggests adiponectin plays a role in the relationship between obesity and insulin resistance, and also insulin resistance and cardiovascular disease, is examined. Variation in the adiponectin gene is one tool to determine whether this relationship is causal. The association of identified variants with human disease, specifically obesity and its consequences, type 2 diabetes and cardiovascular disease is reviewed. This data may enable patients at greater risk of the adverse effects of obesity to be identified and, as such, benefit from more targeted therapy of its consequences.

Adiponectin↗
PubMed2006

Lp-PLA2 activity and PLA2G7 A379V genotype in patients with diabetes mellitus.

Lipoprotein associated phospholipase A2 (Lp-PLA2) modulates low-density lipoprotein (LDL) oxidation by hydrolysing oxidised phospholipids present on particle surfaces. We investigated whether Lp-PLA2 activity and PLA2G7 A379V genotype were related to mediators of atherosclerosis in a diabetic study. Plasma Lp-PLA2 activity (taken in men only) and A379V genotype were investigated with regards to metabolic syndrome (MS), UKPDS risk score, and oxidised LDL (oxLDL/LDL), in a cohort of Caucasian men and women (n=783, age 62.5+/-13.7 years). After adjustment for type of diabetes, CHD status, and statin use, those individuals with features defining the MS (WHO guidelines) had higher Lp-PLA2 activity (35.6+/-11.9 nmol/min/ml) compared to those without (33.0+/-10.8 nmol/min/ml) (p=0.02). Quartiles of UKPDS coronary heart disease (CHD) risk score were also positively associated with Lp-PLA2 activity (p=0.006, p=0.004 linear trend). Those men in the highest quartile of oxLDL/LDL level had the lowest Lp-PLA2 activity (31.3+/-10.5 nmol/min/ml) when compared to the middle two (32.3+/-9.8 and 35.9+/-10.9 nmol/min/ml, respectively) and lowest quartile (35.6 +/-12.5 nmol/min/ml; p=0.03, p=0.004 linear trend). There was no significant association between A379V genotype and Lp-PLA2 enzyme activity (p=0.34) or oxLDL/LDL (p=0.32). Lp-PLA2 activity is an independent predictor of CHD risk and MS in a sample of subjects with diabetes mellitus. The association of Lp-PLA2 activity with oxLDL/LDL suggests that Lp-PLA2 may be a modulating factor in the process of atherosclerosis.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2006

Apo B versus cholesterol in estimating cardiovascular risk and in guiding therapy: report of the thirty-person/ten-country panel.

There is abundant evidence that the risk of atherosclerotic vascular disease is directly related to plasma cholesterol levels. Accordingly, all of the national and transnational screening and therapeutic guidelines are based on total or LDL cholesterol. This presumes that cholesterol is the most important lipoprotein-related proatherogenic risk variable. On the contrary, risk appears to be more directly related to the number of circulating atherogenic particles that contact and enter the arterial wall than to the measured concentration of cholesterol in these lipoprotein fractions. Each of the atherogenic lipoprotein particles contains a single molecule of apolipoprotein (apo) B and therefore the concentration of apo B provides a direct measure of the number of circulating atherogenic lipoproteins. Evidence from fundamental, epidemiological and clinical trial studies indicates that apo B is superior to any of the cholesterol indices to recognize those at increased risk of vascular disease and to judge the adequacy of lipid-lowering therapy. On the basis of this evidence, we believe that apo B should be included in all guidelines as an indicator of cardiovascular risk. In addition, the present target adopted by the Canadian guideline groups of an apo B <90 mg dL(-1) in high-risk patients should be reassessed in the light of the new clinical trial results and a new ultra-low target of <80 mg dL(-1) be considered. The evidence also indicates that the apo B/apo A-I ratio is superior to any of the conventional cholesterol ratios in patients without symptomatic vascular disease or diabetes to evaluate the lipoprotein-related risk of vascular disease.

Apolipoproteins B↗
PubMed2006

Genetic causes of familial hypercholesterolaemia in patients in the UK: relation to plasma lipid levels and coronary heart disease risk.

AIMS: To determine the relative frequency of mutations in three different genes (low-density lipoprotein receptor (LDLR), APOB, PCSK9), and to examine their effect in development of coronary heart disease (CHD) in patients with clinically defined definite familial hypercholesterolaemia in UK. PATIENTS AND METHODS: 409 patients with familial hypercholesterolaemia patients (158 with CHD) were studied. The LDLR was partially screened by single-strand conformational polymorphism (SSCP) (exons 3, 4, 6-10 and 14) and by using a commercial kit for gross deletions or rearrangements. APOB (p.R3500Q) and PCSK9 (p.D374Y) were detected by specific assays. Coding exons of PCSK9 were screened by SSCP. RESULTS: Mutations were detected in 253 (61.9%) PATIENTS: 236 (57.7%) carried LDLR, 10 (2.4%) carried APOB p.Q3500 and 7 (1.7%) PCSK9 p.Y374. No additional mutations were identified in PCSK9. After adjusting for age, sex, smoking and systolic blood pressure, compared to those with no detectable mutation, the odds ratio of having CHD in those with an LDLR mutation was 1.84 (95% CI 1.10 to 3.06), for APOB 3.40 (0.71 to 16.36), and for PCSK9 19.96 (1.88 to 211.5; p = 0.001 overall). The high risk in patients carrying LDLR and PCSK9 p.Y374 was partly explained by their higher pretreatment cholesterol levels (LDLR, PCSK9 and no mutation, 10.29 (1.85), 13.12 and 9.85 (1.90) mmol/l, respectively, p = 0.001). The post-statin treatment lipid profile in PCSK9 p.Y374 carriers was worse than in patients with no identified mutation (LDL-C, 6.77 (1.82) mmol/l v 4.19 (1.26) mmol/l, p = 0.001, HDL-C 1.09 (0.27) mmol/l v 1.36 (0.36) mmol/l, p = 0.03). CONCLUSIONS: The higher CHD risk in patients carrying PCSK9 p.Y347 or a detected LDLR mutation supports the usefulness of DNA testing in the diagnosis and management of patients with familial hypercholesterolaemia. Mutations in PCSK9 appear uncommon in patients with familial hypercholesterolaemia in UK.

Adult↗
PubMed2006

Cascade screening for familial hypercholesterolaemia: implications of a pilot study for national screening programmes.

OBJECTIVES: To determine what proportion of cases of heterozygous familial hypercholesterolaemia would be identified by cascade screening conducted by a specialist hospital clinic, and by how much this would increase the prevalence of diagnosed cases. SETTING: Hospital clinic serving a population of 605,900 in Oxfordshire, UK. METHODS: A specialist nurse obtained details of living first-degree relatives from 227 adult patients with heterozygous familial hypercholesterolaemia currently or previously attending Oxford lipid clinic after excluding 79 adults without relatives living in Oxfordshire and 48 children. Index cases were asked to invite relatives resident in Oxfordshire for testing. RESULTS: A total of 227 index cases had 1075 first-degree relatives, including 442 adults and 117 children aged < 18 years resident in Oxfordshire. We excluded 171 previously screened adults and 46 for other reasons. Among 225 eligible adult relatives, 28 responders (12%) planned to consult their general practitioner and 52 (23%) attended the clinic for testing. Parents of 113 children (97%) wanted them tested. The positive diagnostic rate was 29% (15/52) in adults and 32% (36/113) in children. Screening increased prevalence by 14.4%, from 0.58/1000 (95% confidence intervals [CI] 0.52-0.65) to 0.67/1000 (95% CI 0.60-0.73), representing 33.5% of predicted cases. CONCLUSIONS: Cascade screening conducted by a specialist hospital clinic within its population catchment area did not substantially increase the prevalence of diagnosed familial hypercholesterolaemia. To maximize response rates, clinic staff need to approach relatives directly. Validated age, sex and country-specific diagnostic criteria should be defined, possibly with access to DNA-based tests, to help resolve diagnostic uncertainty.

Adult↗
PubMed2005

APOE polymorphism, socioeconomic status and cognitive function in mid-life--the Whitehall II longitudinal study.

OBJECTIVE: The aim of this study was to investigate the association of the common apolipoprotein E gene (APOE) variants with cognitive function and cognitive decline in adult mid-life and explore the possibility that APOE genotype mediates the link between socioeconomic status (SES) and cognitive function. METHODS: Data on cognitive function, as measured by five cognitive tests, together with APOE genotype were obtained in an occupational cohort (the Whitehall II study) of 6,004 participants aged 44-69 years (1997-1999). Cognitive change was examined in 2,717 participants who had cognitive function measured at baseline (1991-1993). RESULTS: SES based on civil service employment grade was strongly related to cognitive function. There was no association between APOE genotype and employment grade. In women, participants with APOE-epsilon4 had a lower memory score (p<0.05), but the result was sensitive to data from a small number of individuals. A marginal cross-sectional difference in the semantic fluency score was found (p=0.07), and there was a relative decline at follow-up (p<0.001, net change=-1.19; 95% CI, -1.90 to -0.49) in those with APOE-epsilon4 genotypes. CONCLUSIONS: APOE-epsilon4 has little influence on cognitive decline in mid-life, whereas SES is a strong determinant, although APOE genotype may emerge as an important factor in cognitive function in later life.

Adult↗
PubMed2005

Cholesteryl ester transfer protein TaqIB variant, high-density lipoprotein cholesterol levels, cardiovascular risk, and efficacy of pravastatin treatment: individual patient meta-analysis of 13,677 subjects.

BACKGROUND: Several studies have reported that the cholesteryl ester transfer protein (CETP) TaqIB gene polymorphism is associated with HDL cholesterol (HDL-C) levels and the risk of coronary artery disease (CAD), but the results are inconsistent. In addition, an interaction has been implicated between this genetic variant and pravastatin treatment, but this has not been confirmed. METHODS AND RESULTS: A meta-analysis was performed on individual patient data from 7 large, population-based studies (each >500 individuals) and 3 randomized, placebo-controlled, pravastatin trials. Linear and logistic regression models were used to assess the relation between TaqIB genotype and HDL-C levels and CAD risk. After adjustment for study, age, sex, smoking, body mass index (BMI), diabetes, LDL-C, use of alcohol, and prevalence of CAD, TaqIB genotype exhibited a highly significant association with HDL-C levels, such that B2B2 individuals had 0.11 mmol/L (0.10 to 0.12, P<0.0001) higher HDL-C levels than did B1B1 individuals. Second, after adjustment for study, sex, age, smoking, BMI, diabetes, systolic blood pressure, LDL-C, and use of alcohol, TaqIB genotype was significantly associated with the risk of CAD (odds ratio=0.78 [0.66 to 0.93]) in B2B2 individuals compared with B1B1 individuals (P for linearity=0.008). Additional adjustment for HDL-C levels rendered a loss of statistical significance (P=0.4). Last, no pharmacogenetic interaction between TaqIB genotype and pravastatin treatment could be demonstrated. CONCLUSIONS: The CETP TaqIB variant is firmly associated with HDL-C plasma levels and as a result, with the risk of CAD. Importantly, this CETP variant does not influence the response to pravastatin therapy.

Cardiovascular Diseases↗