The common single nucleotide polymorphism (SNP) in the FTO (fat mass and obesity associated) gene has been consistently associated with an increased risk of obesity. We investigated whether the SNP rs9939609 (T/A) of the FTO is associated with risk factors of cardiovascular diseases (CVD), including serum levels of C - reactive protein (CRP), the chemokine RANTES (Regulated on Activation, Normal T Cell Expressed and Secreted; CCL5), and serum and lipoprotein lipids in the Finnish Diabetes Prevention Study (DPS). Furthermore, we examined whether the rs9939609 increased the CVD risk in the DPS and if these results could be replicated in a larger cross-sectional population-based random sample of Finnish men (the METSIM).
In the DPS, altogether 490 (BMI=25kg/m(2)) subjects with impaired glucose tolerance were genotyped for rs9939609. Cardiovascular morbidity and mortality data were collected during the median follow-up of 10.2 years. The replication study was a population-based cross-sectional study of 6214 men. In the DPS, the AA genotype of rs9939609 was associated, independently of BMI, with increased RANTES (p=0.002) and decreased HDL cholesterol concentrations (p=0.007) in men. During the follow-up, the AA genotype was associated with an adjusted 2.09-fold risk (95% CI 1.17-3.73, p=0.013) of CVD in men. In the METSIM Study, the association with a history of myocardial infarction was replicated in the subgroup of men with type 2 diabetes.
We suggest that the variation in the FTO gene may contribute to the development of CVD in men with an abnormal glucose metabolism.
BACKGROUND: Exposure to cold weather increases blood pressure (BP) and may aggravate the symptoms and influence the prognosis of subjects with a diagnosis of hypertension. We tested the hypothesis that subjects with hypertension alone or in combination with another cardiovascular disease (CVD) experience cold-related cardiorespiratory symptoms more commonly than persons without hypertension. This information is relevant for proper treatment and could serve as an indicator for predicting wintertime morbidity and mortality.
METHODS: A self-administered questionnaire inquiring of cold-related symptoms was obtained from 6591 men and women aged 25-74 yrs of the FINRISK Study 2002 population. BP was measured in association with clinical examinations. Symptom prevalence was compared between subjects with diagnosed hypertensive disease with (n = 395) or without (n = 764) another CVD, untreated diagnosed hypertension (n = 1308), measured high BP (n = 1070) and a reference group (n = 2728) with normal BP.
RESULTS: Hypertension in combination with another CVD was associated with increased cold-related dyspnoea (men: adjusted odds ratio 3.94, 95% confidence interval 2.57-6.02)/women: 4.41, 2.84-6.86), cough (2.64, 1.62-4.32/4.26, 2.60-6.99), wheezing (2.51, 1.42-4.43/;3.73, 2.08-6.69), mucus excretion (1.90, 1.24-2.91/2.53, 1.54-4.16), chest pain (22.5, 9.81-51.7/17.7, 8.37-37.5) and arrhythmias (43.4, 8.91-211/8.99, 3.99-20.2), compared with the reference group. Both diagnosed treated hypertension and untreated hypertension and measured high BP resulted in increased cardiorespiratory symptoms during the cold season.
CONCLUSION: Hypertension alone and together with another CVD is strongly associated with cold-related cardiorespiratory symptoms. As these symptoms may predict adverse health events, hypertensive patients need customized care and advice on how to cope with cold weather.
Impaired insulin secretion is a fundamental defect in type 2 diabetes. The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) in the genes regulating insulin secretion (SLC2A2 [encoding GLUT2], GCK, TCF1 [encoding HNF-1alpha], HNF4A, GIP, and GLP1R) are associated with the conversion from impaired glucose tolerance (IGT) to type 2 diabetes in participants of the Finnish Diabetes Prevention Study. With the exception of SLC2A2, other genes were not associated with the risk of type 2 diabetes. All four SNPs of SLC2A2 predicted the conversion to diabetes, and rs5393 (AA genotype) increased the risk of type 2 diabetes in the entire study population by threefold (odds ratio 3.04, 95% CI 1.34-6.88, P = 0.008). The risk for type 2 diabetes in the AA genotype carriers was increased in the control group (5.56 [1.78-17.39], P = 0.003) but not in the intervention group. We conclude that the SNPs of SLC2A2 predict the conversion to diabetes in obese subjects with IGT.