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Cytochrome P450 17A1 (CYP17A1) catalyses the formation and metabolism of steroid hormones. They are involved in blood pressure (BP) regulation and in the pathogenesis of left ventricular hypertrophy. Therefore, altered function of CYP17A1 due to genetic variants may influence BP and left ventricular mass. Notably, genome wide association studies supported the role of this enzyme in BP control. Against this background, we investigated associations between single nucleotide polymorphisms (SNPs) in or nearby the CYP17A1 gene with BP and left ventricular mass in patients with arterial hypertension and associated cardiovascular organ damage treated according to guidelines. Patients (n = 1007, mean age 58.0 +/- 9.8 years, 83% men) with arterial hypertension and cardiac left ventricular ejection fraction (LVEF) 40% were enrolled in the study. Cardiac parameters of left ventricular mass, geometry and function were determined by echocardiography. The cohort comprised patients with coronary heart disease (n = 823; 81.7%) and myocardial infarction (n = 545; 54.1%) with a mean LVEF of 59.9% +/- 9.3%. The mean left ventricular mass index (LVMI) was 52.1 +/- 21.2 g/m(2.7) and 485 (48.2%) patients had left ventricular hypertrophy. There was no significant association of any investigated SNP (rs619824, rs743572, rs1004467, rs11191548, rs17115100) with mean 24 h systolic or diastolic BP. However, carriers of the rs11191548 C allele demonstrated a 7% increase in LVMI (95% CI: 1%-12%, p = 0.017) compared to non-carriers. The CYP17A1 polymorphism rs11191548 demonstrated a significant association with LVMI in patients with arterial hypertension and preserved LVEF. Thus, CYP17A1 may contribute to cardiac hypertrophy in this clinical condition.
Alcohol abuse and dependence have proven to be complex genetic traits that are influenced by environmental factors. Primate and human studies have shown that early life stress increases the propensity for alcohol abuse in later life. The reinforcing properties of alcohol are mediated by dopaminergic signaling; however, there is little evidence to indicate how stress alters alcohol reinforcement. KCNJ6 (the gene encoding G-protein-coupled inwardly rectifying potassium channel 2 (GIRK2)) is a brain expressed potassium channel with inhibitory effects on dopaminergic tone. The properties of GIRK2 have been shown to be enhanced by the stress peptide corticotrophin-releasing hormone. Therefore, we sought to examine the role of KCNJ6 polymorphisms in adult alcohol dependence and stress-related alcohol abuse in adolescents. We selected 11 SNPs in the promoter region of KCNJ6, which were genotyped in 1152 adult alcohol dependents and 1203 controls. One SNP, rs2836016, was found to be associated with alcohol dependence (p = 0.01, false discovery rate). We then assessed rs2836016 in an adolescent sample of 261 subjects, which were characterized for early life stress and adolescent hazardous drinking, defined using the Alcohol Use Disorders Identification Test (AUDIT), to examine gene-environment interactions. In the adolescent sample, the risk genotype of rs2836016 was significantly associated with increased AUDIT scores, but only in those individuals exposed to high levels of psychosocial stress in early life (p = 0.01). Our findings show that KCNJ6 is associated with alcohol dependence and may moderate the effect of early psychosocial stress on risky alcohol drinking in adolescents. We have identified a candidate gene for future studies investigating a possible functional link between the response to stress and alcohol reinforcement.
Common knowledge suggests that growth in height is influenced by nutrition, genetics, health, and environmental and general living conditions. In addition, modern studies showed that also social mobility and dominance within the social group, may significantly affect adolescent growth and final height. The aim of the study was to investigate the impact of popular ideas and beliefs about factors influencing the growth on the biology of child and adolescent growth. We hypothesized that these beliefs are culture-specific and age-dependent. We investigated 307 French and 315 German participants of all age-groups. We collected polarising statements by questionnaire that the participants had to agree or disagree on. French participants see a connection between nutrition and the body height of children. This is different in Germany and may be due to the fact that French food culture is more traditional. Genetic factors were generally overestimated and considered as the most important determinants of longitudinal-growth. The participants denied an influence of disease and social status. Participants over 35 years of age considered adult height to be independent of environmental factors. In conclusion, popular beliefs partly depend on culture and appear to change with age as a result of growing experience.
Objective:Common genetic variants in the gene encoding uromodulin (UMOD) have been associated with renal function, blood pressure (BP) and hypertension. We investigated the associations between an important single nucleotide polymorphism (SNP) in UMOD, that is rs12917707-G>T, and estimated glomerular filtration rate (eGFR), BP and cardiac organ damage as determined by echocardiography in patients with arterial hypertension.Methods:A cohort of 1218 treated high-risk patients (mean age 58.5 years, 83% men) with documented cardiovascular disease (81% with coronary heart disease) was analysed.Results:The mean values for 24-h SBP and DBP were 124.714.7 and 73.9 +/- 9.4mmHg; mean eGFR was 77.5 +/- 18.3ml/min per 1.73m(2), mean left ventricular ejection fraction was 59.3 +/- 9.9% and mean left ventricular mass index in men and women was 53.9 +/- 23.2 and 54.9 +/- 23.7g/m(2.7) with 50.4% of patients having left ventricular hypertrophy. A significant association between rs12917707 and eGFR was observed with T-allele carriers showing significantly higher eGFR values (+2.6ml/min per 1.73m(2), P=0.006) than noncarriers. This SNP associated also with left atrial diameter (P=0.007); homozygous carriers of the T-allele had smaller left atrial diameter (-1.5mm) than other genotype groups (P=0.040). No significant associations between rs12917707 and other cardiac or BP phenotypes were observed.Conclusions:These findings extend the previously documented role of UMOD for renal function also to treated high-risk patients with arterial hypertension and reveal a novel association with left atrial remodelling and thus a potential cardiorenal link modulated by UMOD.