Common NOD2/CARD15 variants are not associated with susceptibility or the clinicopathologic characteristics of sporadic colorectal cancer in Hungarian patients

BACKGROUND: Epidemiological observations suggest that cancer arises from chronically inflamed tissues. Inflammatory bowel disease (IBD) is a typical example as patients with longstanding IBD are at an increased risk for developing colorectal cancer (CRC) and mutations of the NOD2/CARD15 gene increase the risk for Crohn's disease (CD). Recently, NOD2/CARD15 has been associated with a risk for CRC in some studies, which stemmed from ethnically diverse populations. Our aim was to identify common NOD2/CARD15 mutations in Hungarian patients with sporadic CRC. METHODS: A total of 194 sporadic CRC patients (m/f: 108/86, age at diagnosis of CRC: 63.2 ± 9.1 years old) and 200 healthy subjects were included. DNA was screened for SNP8, SNP12 and SNP13 NOD2/CARD15 mutations by denaturing-HPLC and confirmed by direct sequencing. RESULTS: NOD2/CARD15 mutations were found in 28 patients (14.4%) and in 23 controls (11.5%, p = NS). Allele frequencies for SNP8/R702W (1.8% vs. 1.5%) SNP12/G908R (1.8% vs. 1.8%) and SNP13/3020insC (3.6% vs. 2.5%) were also not statistically different between patients and controls. The clinicopathologic characteristics of CRC patients with or without NOD2/CARD15 mutations were not significantly different. CONCLUSION: Our results suggest that common NOD2/CARD15 mutations alone do not contribute to CRC risk in the Hungarian population

A metabolikus szindróma összetevőinek genetikai meghatározottsága: ikervizsgálatok eredményei [Heritability of the risk factors characteristic for the metabolic syndrome: a twin study]

A metabolikus szindrómára jellemző cardiovascularis kockázati tényezők alakulásában örökletes és környezeti tényezők is szerepet kapnak. A genetikai és környezeti tényezők jellegzetességei populációkként változhatnak. Célkitűzés: Az ikervizsgálat célja a metabolikus szindrómában szereplő cardiovascularis kockázati tényezők genetikai, illetve környezeti meghatározottságának megállapítása volt. Módszer: A tanulmányban 101 egészséges felnőtt ikerpár (63 pár monozigóta, 38 pár azonos nemű dizigóta; n = 202, életkor: 43,3±15,8 év) szerepelt. Fizikális vizsgálat után a betegek kérdőívet töltöttek ki, majd éhomi vérvételre került sor. A statisztikai értékelés során a genetikai, a közös és egyéni környezeti determináltság százalékos arányát jelző öröklődési indexek meghatározása történt az A-C-E strukturált egyenletmodell illeszkedése alapján. Az adatok életkorra, nemre (Modell-1), illetve életkorra, nemre, BMI- és haskörfogatértékre korrigáltak (Modell-2). Eredmények: A haskörfogat (illetve a többi antropometriai paraméter [testmagasság, testsúly]) alakulása terén egyértelműen dominált a genetikai meghatározottság (Modell-1-érték: 71,0–88,1%). Kevésbé markánsan voltak az örökletes tényezők a meghatározók a szisztolés és a diasztolés vérnyomásérték alakulására (Modell-2-érték: 57,1% és 57,7%). A Modell-2-érték alapján az egyéni környezeti tényezők játszottak jelentősebb szerepet a szérumtriglicerid értékének (55,9%) alakulásában, míg a közös környezeti determináltság volt a meghatározó a szérum-HDL-koleszterin (58,1%) és az éhomi vércukor (57,1%) értékének alakulásában. A Modell-1- és Modell-2-értékek összehasonlítása arra utalt, hogy az antropometriai paraméterek (BMI, haskörfogat) csak kis hányadban (0,0–17,1%) kaptak szerepet a metabolikus szindróma genetikai és környezeti összetevőinek determináltságában. Következtetések: Felnőtt, magukat egészségesnek tartó egyének körében a metabolikus szindróma komponensei között a genetikai tényezőknek meghatározó szerepe van a haskörfogat és a vérnyomás alakulása terén, míg a szérumtriglicerid-, a HDL-koleszterin- és az éhomi vércukorérték alakulására környezeti tényezők vannak elsősorban befolyással. Az egyes kockázati tényezők eltérő öröklődése kétségessé teszi a metabolikus szindróma eredeti, egységes kóroktanon alapuló koncepciójának helyességét. A vizsgálat eredményei egyéni és társadalmi szinten egyaránt segíthetik a primer cardiovascularis prevenció megtervezését és kivitelezését. Orv. Hetil., 2011, 152, 1265–1271. | Both genetic and environmental factors play role in the pathogenesis of the metabolic syndrome. The magnitude of genetic and environmental influences on the components of metabolic syndrome may vary in different populations. Aims: The present study was aimed to determine the effects of genetic and environmental factors on risk factors characteristic for the metabolic syndrome. Methods: A total of 101 (63 monozygotic and 38 dizygotic) adult twin pairs (n = 202; mean age: 43.3±15.8 years) were investigated. Medical history was recorded and physical examination was carried out for each subject. Fasting venous blood samples were used for measuring laboratory parameters. The presented estimates include the heritability structural equation (A-C-E) model results. In Model-1, all presented parameters are age- and gender- corrected. In Model-2, parameters were corrected for age, gender, body mass index and waist circumference. Results: Heritability in waist circumference (as well as in other anthropometric parameters such as weight and height) was high (Model-1: 71.0–88.1%). Similarly, genetic factors had the highest proportion of total phenotypic variance in systolic and diastolic blood pressure (Model-2: 57.1% and 57.7%, respectively). Based on the results of Model-2, unique environmental factors dominate alterations in serum triglycerides values (55.9%) while shared environmental factors proved to be substantial in alterations of HDL-cholesterol and fasting blood glucose values (58.1% and 57.1%, respectively). Comparing the results of Model-1 and Model-2, the difference in A-C-E model varied from 0.0% to 17.1%, indicating that only a minor proportion of genetic and environmental influences can be explained by the effects of anthropometric parameters. Conclusions: Among adult Hungarian healthy people, genetic factors have substantial influence on waist circumference and blood pressure values while environmental factors dominate alterations in serum triglycerides, HDL-cholesterol and fasting blood glucose values. The different heritability of individual risk factors challenges the original unifying concept of the metabolic syndrome. The results may be useful for establishing and implementing primary cardiovascular prevention both at individual and population levels. Orv. Hetil., 2011, 152, 1265–1271

Sex-dependent alterations in erythrocyte trace element levels and antioxidant status after a month of moderate daily red wine consumption

Objective We tested the hypothesis whether trace elements and antioxidant status change in a sex-dependent manner may contribute to sex-dependent hepatic effects of moderate daily wine consumption. Patient and methods Twenty-one healthy young men and women were enrolled to this study who consumed red wine 0.3 and 0.21 per day, respectively, for a month. Blood was taken at baseline (BV) and at end of the study (EV). Red cell trace element levels, red cell and plasma antioxidant status and serum routine blood chemistry were assessed at baseline and at the end of the study. Results No sign of hepatotoxicity was detected. BV level of some trace elements (i.e. Zn, Pb) and Zn/Cu ratios were higher in women than in men. Ca, Mg, Pb, Sir and Zn levels and the Zn/Cu ratio had lower EV than BV in women. In men, Al, Ca, Li, Pb and Sir levels had lower EV than BV. The tested antioxidant parameters improved in both the sexes. Conclusion Although no hepatotoxicity was observed, changes in trace element content were detected after 1 month of moderate red wine consumption. The most remarkable sex-specific alteration was the decrease of Zn levels and of the Zn/Cu ratio in women. Given the protective effect of Zn against liver damage, this finding suggests a possible contribution of decreased Zn levels to sex-dependent effects of red wine. Eur J Gastroenterol Hepatol 22:185-191 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins

Twins Lead to the Prevention of Atherosclerosis: Preliminary Findings of International Twin Study 2009

ABSTRACT Introduction.—Atherosclerosis is an infl ammatory process in which the artery wall thickens as a result of plaque deposition, but this process may be preceded by increased arterial stiffness. We sought to evaluate the infl uence of genetics and shared and unshared environmental components on the onset of atherosclerosis. Methods.—A total of 135 monozygotic (MZ) and 70 dizygotic (DZ) twin pairs (mean age 49 ± 16 years) underwent carotid intima media thickness (IMT; carotid analyzer) and arterial stiffness (augmentation index on brachial artery [Aixbra], pulse wave velocity on aorta [PWVao]; TensioMed Arteriograph) measurements. Results.—Age-adjusted intraclass correlations were greater in MZ than in DZ pairs for proximal right common carotid artery (CCA; MZ = 0.19, DZ = 0.06), proximal and distal left CCA (MZ = 0.27, DZ = 0.06; MZ = 0.27, DZ = 0.13, respectively), and proximal left internal carotid artery (ICA; MZ = 0.39, DZ = −0.54), suggesting a moderate genetic effect. Heritability was estimated to be 18% (95% confi dence interval [CI] = 3–33) for proximal right CCA, 26% and 27% for proximal and distal left CCA, respectively, and 38% (95% CI = 26–49) for proximal left ICA. Regarding distal right CCA and proximal right ICA, no genetic effects were detected. Age-adjusted intraclass correlation of Aixbra and PWVao were 0.65 (95% CI = 0.55–0.72) and 0.46 (95% CI = 0.33–0.57) in MZ, 0.42 (95% CI = 0.24–0.57) and 0.28 (95% CI = 0.08–0.47) in DZ pairs; heritability 45% (95% CI = 12–71%) and 42% (95% CI = 2–57%) adjusted by age, respectively. Conclusions.—The investigated parameters appeared to be only moderately infl uenced by genetic factors. Environmental factors of relevance for these measures appeared not to be shared within family but related to individual experience (e.g., smoking habits, diet, and physical activity). Atherosclerosis detection at an early stage is necessary for treatment to prevent serious complications such as stroke and heart attack