Haptoglobin polymorphism as a risk factor for coronary heart disease mortality

Objectives: the aim of our study was to evaluate the independent role of the haptoglobin (Hp) polymorphism as a risk factor for coronary heart disease (CHD) mortality. Methods: within the framework of the longitudinal part of the Belgian Interuniversity Research on Nutrition and Health (BIRNH) survey, a nested case-control study design was performed through matching the 107 deaths from CHD, occurring within a 10-year follow-up period, with three controls for age and gender. Results: the distribution of the Hp types was found to be in Hardy-Weinberg equilibrium. Conditional logistic regression analysis for matched sets revealed that the Hp polymorphism was significantly associated with CHD death. Rather surprisingly, the finding was that Hp 1-1 individuals were at doubled risk for CHD mortality compared with the others, the odds ratio being 2.09 (95% CI: 1.22-3.60). The association was independent from other classical cardiovascular risk factors and the Hp concentration, and of comparable magnitude between men and women. Moreover, evaluating the interaction term in a multiplicative model showed that the Hp type did not play a synergistic role in the prognostic value of established cardiovascular risk factors. Conclusion: in contrast to the findings from cross-sectionally based studies, the results from this longitudinal study show that Hp 1-1 individuals are at elevated risk for CHD mortality. © 2001 Elsevier Science Ireland Ltd.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Human metabolic phenotype diversity and its association with diet and blood pressure

Metabolic phenotypes are the products of interactions among a variety of factors- dietary, other lifestyle/environmental, gut microbial and genetic. We use a large-scale exploratory analytical approach to investigate metabolic phenotype variation across and within four human populations, based on 1H NMR spectroscopy. Metabolites discriminating across populations are then linked to data for individuals on blood pressure, a major risk factor for coronary heart disease and stroke (leading causes of mortality worldwide). We analyse spectra from two 24-hour urine specimens for each of 4,630 participants from the INTERMAP epidemiological study, involving 17 population samples aged 40-59 in China, Japan, UK and USA. We show that urinary metabolite excretion patterns for East Asian and western population samples, with contrasting diets, diet-related major risk factors, and coronary heart disease/stroke rates, are significantly differentiated (P < 10 -16), as are Chinese/Japanese metabolic phenotypes, and subgroups with differences in dietary vegetable/animal protein and blood pressure. Among discriminatory metabolites, we quantify four and show association (P < 0.05 to P < 0.0001) of mean 24-hour urinary formate excretion with blood pressure in multiple regression analyses for individuals. Mean 24-hour urinary excretion of alanine (direct) and hippurate (inverse), reflecting diet and gut microbial activities, are also associated with blood pressure of individuals. Metabolic phenotyping applied to high-quality epidemiological data offers the potential to develop an area of aetiopathogenetic knowledge involving discovery of novel biomarkers related to cardiovascular disease risk