Browsing by Author "Paulweber, Bernhard"
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Item Genetic architecture of the APM1 gene and its influence on adiponectin plasma levels and parameters of the metabolic syndrome in 1,727 healthy Caucasians(2006-02) Heid, Iris M.; Wagner, Stefanie A.; Gohlke, Henning; Iglseder, Bernhard; Cip, Paula; Ladurner, Günther; Mackevics, Vitolds; Illig, Thomas; Kronenberg, Florian; Paulweber, BernhardThe associations of the adiponectin (APM1) gene with parameters of the metabolic syndrome are inconsistent. We performed a systematic investigation based on fine-mapped single nucleotide polymorphisms (SNPs) highlighting the genetic architecture and their role in modulating adiponectin plasma concentrations in a particularly healthy population of 1,727 Caucasians avoiding secondary effects from disease processes. Genotyping 53 SNPs (average spacing of 0.7 kb) in the APM1 gene region in 81 Caucasians revealed a two-block linkage disequilibrium (LD) structure and enabled comprehensive tag SNP selection. We found particularly strong associations with adiponectin concentrations for 11 of the 15 tag SNPs in the 1,727 subjects (five P values <0.0001). Haplotype analysis provided a thorough differentiation of adiponectin concentrations with 9 of 17 haplotypes showing significant associations (three P values <0.0001). No significant association was found for any SNP with the parameters of the metabolic syndrome. We observed a two-block LD structure of APM1 pointing toward at least two independent association signals, one including the promoter SNPs and a second spanning the relevant exons. Our data on a large number of healthy subjects suggest a clear modulation of adiponectin concentrations by variants of APM1, which are not merely a concomitant effect in the course of type 2 diabetes or coronary artery disease.Item Plasma adiponectin levels and sonographic phenotypes of subclinical carotid artery atherosclerosis : Data from the SAPHIR study(2005-12) Iglseder, Bernhard; Mackevics, Vitolds; Ladurner, Gunther; Paulweber, BernhardBackground and Purpose - Adipose tissue produces and secretes a number of bioactive molecules, conceptualized as adipocytokines. Adiponectin has been identified as one of the adipocytokines, and hypoadiponectinemia was demonstrated in patients with obesity, diabetes mellitus, and coronary artery disease. Whether decreased adiponectin levels are cause or consequence is an important issue in the discussion on the association between adiponectin and atherosclerosis. In the present study, we investigated the association of plasma adiponectin levels with sonographic phenotypes of subclinical atherosclerosis, which may represent different stages of disease as well as common and distinct determinants. Methods - A total of 1515 middle-aged healthy white subjects (940 males and 575 females) were included. Common carotid artery intima-media thickness (CIMT) and presence of atherosclerotic plaques were assessed by B-mode ultrasound. Results - After adjustment for established risk factors, per 1 μg/mL decrease in adiponectin CIMT increased on the average by 3.48 μ in males (95% CI, 1.23 to 5.73 μm) and by 2.39 μ in females (95% CI, 0.50 to 4.27 μm). After dichotomizing adiponectin levels at the median and adjustment for established risk factors, the mean difference of CIMT between subjects with low and high adiponectin levels was 20.42 μm in men (95% CI, 6.80 to 34.04; P=0.003) and 20.75 μ in women (95% CI, 1.08 to 40.42; P=0.039). No significant relationship was found between adiponectin levels and presence of atherosclerotic plaques. Conclusion - Our results demonstrate an independent negative association of adiponectin levels and CIMT, whereas no relationship with presence of atherosclerotic plaques was found, thus suggesting hypoadiponectinemia as a risk factor in the development of early atherosclerosis.Item Response to letter by Pilz et al(2006-07) Iglseder, Bernhard; Ladurner, Gunther; Mackevics, Vitolds; Paulweber, Bernhard