Marilyn C. Cornelis

Coffee, caffeine, and coronary heart disease

Purpose of review This review summarizes and highlights recent advances in current knowledge of the relationship between coffee and caffeine consumption and risk of coronary heart disease. Potential mechanisms and genetic modifiers of this relationship are also discussed. Recent findings Studies examining the association between coffee consumption and coronary heart disease have been inconclusive. Coffee is a complex mixture of compounds that may have either beneficial or harmful effects on the cardiovascular system. Randomized controlled trials have confirmed the cholesterol-raising effect of diterpenes present in boiled coffee, which may contribute to the risk of coronary heart disease associated with unfiltered coffee consumption. A recent study examining the relationship between coffee and risk of myocardial infarction incorporated a genetic polymorphism associated with a slower rate of caffeine metabolism and provides strong evidence that caffeine also affects risk of coronary heart disease. Several studies have reported a protective effect of moderate coffee consumption, which suggests that coffee contains other compounds that may be beneficial. Summary Diterpenes present in unfiltered coffee and caffeine each appear to increase risk of coronary heart disease. A lower risk of coronary heart disease among moderate coffee drinkers might be due to antioxidants found in coffee.

Coffee, caffeine, and coronary heart disease.

Purpose of reviewThis review summarizes and highlights recent advances in current knowledge of the relationship between coffee and caffeine consumption and risk of coronary heart disease. Potential mechanisms and genetic modifiers of this relationship are also discussed. Recent findingsStudies examining the association between coffee consumption and coronary heart disease have been inconclusive. Coffee is a complex mixture of compounds that may have either beneficial or harmful effects on the cardiovascular system. Randomized controlled trials have confirmed the cholesterol-raising effect of diterpenes present in boiled coffee, which may contribute to the risk of coronary heart disease associated with unfiltered coffee consumption. A recent study examining the relationship between coffee and risk of myocardial infarction incorporated a genetic polymorphism associated with a slower rate of caffeine metabolism and provides strong evidence that caffeine also affects risk of coronary heart disease. Several studies have reported a protective effect of moderate coffee consumption, which suggests that coffee contains other compounds that may be beneficial. SummaryDiterpenes present in unfiltered coffee and caffeine each appear to increase risk of coronary heart disease. A lower risk of coronary heart disease among moderate coffee drinkers might be due to antioxidants found in coffee.

Genetic polymorphism of CYP1A2 increases the risk of myocardial infarction

Background: There is growing evidence that DNA damage caused by mutagens found in tobacco smoke may contribute to the development of coronary heart disease (CHD). In order to bind to DNA many mutagens require metabolic activation by cytochrome P450 (CYP) 1A1 or CYP1A2. The objective of this study was to determine the effects of CYP1A1 and CYP1A2 genotypes on risk of myocardial infarction (MI) and whether smoking interacts with genotype to modify risk. Methods: Subjects (n = 873) with a first acute non-fatal MI and population based controls (n = 932) living in Costa Rica, matched for age, sex, and area of residence, were genotyped for CYP1A1*2A and CYP1A2*1F by restriction-fragment length polymorphism (RFLP)-PCR, and smoking status was determined by questionnaire. Results: After adjusting for matching variables and potential confounders, no association was observed between CYP1A1 genotype and risk of MI. Compared to individuals with the high inducibility CYP1A2*1A/*1A genotype, the adjusted odds ratio and 95% confidence intervals for risk of MI were 1.19 (0.97 to 1.47) for the *1A/*1F genotype and 1.55 (1.10 to 2.18) for the *1F/*1F genotype. No significant interactions were observed between smoking and either CYP1A1 or CYP1A2 genotype. Conclusions: The low inducibility genotype for CYP1A2 was associated with an increased risk of MI. This effect was independent of smoking status and suggests that a substrate of CYP1A2 that is detoxified rather than activated may play a role in CHD.

Nutrigenomics of Taste – Impact on Food Preferences and Food Production

Food preferences are influenced by a number of factors such as personal experiences, cultural adaptations and perceived health benefits. Taste, however, is the most important determinant of how much a food is liked or disliked. Based on the response to bitter-tasting compounds such as phenylthiocarbamide (PTC) or 6-n-propylthiouracil (PROP), individuals can be classified as supertasters, tasters or nontasters. Sensitivity to bitter-tasting compounds is a genetic trait that has been recognized for more than 70 years. Genetic differences in bitter taste perception may account for individual differences in food preferences. Other factors such as age, sex and ethnicity may also modify the response to bitter-tasting compounds. There are several members of the TAS2R receptor gene family that encode taste receptors on the tongue, and genetic polymorphisms of TAS2R38 have been associated with marked differences in the perception of PTC and PROP. However, the association between TAS2R38 genotypes and aversion to bitter-tasting foods is not clear. Single nucleotide polymorphisms in other taste receptor genes have recently been identified, but their role in bitter taste perception is not known. Establishing a genetic basis for food likes/dislikes may explain, in part, some of the inconsistencies among epidemiologic studies relating diet to risk of chronic diseases. Identifying populations with preferences for particular flavors or foods may lead to the development of novel food products targeted to specific genotypes or ethnic populations.

Glutathione S-transferase genotype and risk of systemic lupus erythematosus in Koreans

Oxidative stress caused by poor detoxification efficiency of reactive oxygen species (ROS) may play a role in the development of systemic lupus erythematosus (SLE). Glutathione S-transferase (GST) is involved in the detoxification of ROS and genetic polymorphisms of GSTM1, GSTT1 and GSTP1 are associated with altered enzyme activity. The aim of this study was to determine whether GSTM1 (deletion), GSTT1 (deletion) and GSTP1 (Ile105! Val105) polymorphisms are associated with susceptibility to SLE or frequency of clinical manifestations according to the ACR diagnostic criteria. DNA was isolated from blood samples collected from 330 patients with SLE and 270 ageand sex-matched controls. GST genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. No associations were observed between GSTM1, GSTT1, and GSTP1 genotypes and risk of SLE. Among SLE patients, the GSTM1 null genotype was associated with a lower frequency of hematological disorders (P = 0.012), and a higher SSA(+)/SSB(2) autoantibody profile (P = 0.042). Compared to SLE patients with the GSTT1 non-null genotype, those with the GSTT1 null genotype had a lower frequency of discoid rash (P = 0.018), and nephritis (P = 0.033). Our findings suggest that genetic polymorphisms of GSTM1, GSTT1, and GSTP1 do not influence the risk of SLE, but a deletion of either GSTM1 or GSTT1 may influence certain clinical manifestations of the disease.

Glutathione S-transferase M1, T1, and P1 gene polymorphisms and carotid atherosclerosis in Korean patients with rheumatoid arthritis

AbstractWe assessed the contribution of genetic polymorphisms of glutathione S-transferase M1 (GSTM1), T1 (GSTT1), and P1 (GSTP1, Ile105Val) to carotid atherosclerosis in 40 postmenopausal rheumatoid arthritic (RA) women without histories of smoking. We measured mean intima-media thickness (IMT) and plaque of the common carotid arteries by ultrasonography and evaluated relationships among the known risk factors for atherosclerosis, genetic polymorphisms, RA outcomes, and markers of inflammation. Subjects with the GSTT1–0 genotype had greater IMT (P<0.05). On univariate analysis, carotid IMT was positively associated with age, systolic BP, antihypertensive drug use, and the GSTT1–0 genotype (P<0.05). When compared to subjects with a double-positive GSTM1/T1 genotype, IMT in those with concurrent lack of the GSTM1 and GSTT1 genes was significantly increased (P=0.008). This study suggests that the GSTT1–0 genotype might have an interaction with carotid atherosclerosis related to RA in Korean postmenopausal RA women without histories of smoking.

TAS2R38 Genotypes and Phenylthiocarbamide Bitter Taste Perception in a Population of Young Adults

Background/Aims:TAS2R38 belongs to the TAS2R bitter taste receptor gene family and polymorphisms are associated with differences in bitter taste perception of phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP). The objectives were to test whether the genotype-phenotype relationship varies between ethnocultural groups and whether a filter paper method can predict TAS2R38 genotype. Methods: Subjects (n = 911) aged 20–29 rated the intensity of a PTC-containing filter paper on a scale of 1–9, from ‘not at all bitter’ to ‘extremely bitter’. The TAS2R38 A49P polymorphism was detected by real-time PCR. Results: The overall frequency of the 49A variant was 0.47 and the AA, AP, and PP genotype distribution was 0.24, 0.45 and 0.31, respectively. Those with AA, AP, or PP genotypes had mean bitterness rating scores of 2.3, 4.9, and 5.9, respectively. The 49A variant frequency was significantly lower among Asians (28%) as compared to Caucasians (55%), South Asians (60%) or others (56%) (p < 0.0001). The genotype-phenotype relationship was similar across ethnocultural groups, however, a stronger genotype-phenotype association was observed among women as compared to men. Conclusion: Our findings show that a simple PTC filter paper tasting method strongly predicts TAS2R38 genotype, and that the genotype-phenotype association is similar among ethnocultural groups.

Catalase and PPARγ2 genotype and risk of rheumatoid arthritis in Koreans

Catalase (CAT) and peroxisome proliferator activated receptor-γ2 (PPARγ2) are important regulators of oxidative stress and inflammation, and may contribute to the development of rheumatoid arthritis (RA). We investigated the association between CAT and PPARγ2 genotypes and risk and severity of RA using 474 cases and 400 controls. Genotyping for the −262C→T polymorphism of CAT and the Pro12Ala polymorphism of PPARγ2 was performed by PCR-RFLP analysis. Severity of RA was assessed by the anatomical stage according to Steinbrocker, and a Korean language version of a Health Assessment Questionnaire (KHAQ). No association was observed between CAT and PPARγ2 genotypes and risk of RA. Our results suggest that genetic polymorphisms of CAT and PPARγ2 do not play a significant role in the susceptibility to RA among Koreans.

Catalase and PPARg2 genotype and risk of systemic lupus erythematosus in Koreans

Catalase (CAT) and peroxisome proliferator activated receptor-g2 (PPARg2) are important regulators of oxidative stress and inflammation, which may contribute to the development of systemic lupus erythematosus (SLE). The objective of this study was to investigate the effects of genetic polymorphisms of CAT and PPARg2 on risk and severity of SLE in a Korean population. DNA was isolated from blood samples collected from 345 patients with SLE and 400 controls. Genotyping for the 2262C!T polymorphism of CAT and the Pro12Ala polymorphism of PPARg2 were performed by PCR-RFLP analysis. The severity of SLE was assessed using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index (SDI). No association was observed between genotypes for any of the clinical manifestations of SLE. CAT and PPARg2 genotypes were not associated with either risk or severity of SLE. For subjects who were carriers of the high activity Tallele for CATand have the Pro/Pro genotype for PPARg2, the odds ratio (95% confidence interval) for risk of SLE was 0.45 (0.23-1.08). Our results suggest that genetic polymorphisms of CAT and PPARg2 do not play a significant role in the development of SLE in a Korean population. A possible protective effect of a combined genotype warrants further investigation.