Gln27Glu variant of Beta2-adrenoceptor gene affects male type fat accumulation in women

<p>Abstract</p> <p>Background</p> <p>The β₂-adrenergic receptor (BAR2) is the main lipolytic receptor in white human adipose tissue. There is a functional glutamine 27 glutamic acid (Gln27Glu, rs 1042714) polymorphism in its gene, which has been variably associated with body mass index. This gene variant may be associated with male-type adiposity in women and thus increased cardiovascular risk. We investigated whether the BAR2 Gln27Glu polymorphism is associated with visceral fat and coronary intima thickness in women.</p> <p>Methods</p> <p>The amount of mesenteric and omental fat was directly measured and anthropometric measurements were done from 112 forensic autopsy cases of women aged 15 to 49 years. The thickness of the coronary intima, which reflects the severity of atherosclerosis, was measured by computerized image analysis. The BAR2 Gln27Glu polymorphism was determined by polymerase chain reaction.</p> <p>Results</p> <p>We found that the amount of visceral fat was significantly higher in women with the Glu allele (689 ± 555 g) compared to Gln/Gln homozygotes (481 ± 392 g, P = 0.023). The waist-hip ratio also tended to be higher in women with the Glu allele compared to Gln/Gln homozygotes (p = 0.050). There were no statistically significant differences between the genotype groups in BMI or the thickness of coronary intima.</p> <p>Conclusion</p> <p>The Glu allele of the BAR2 gene may be a risk factor for visceral fat accumulation in young to middle-aged women. However, this polymorphism was not associated with preclinical atherosclerosis.</p

Common Inflammation-Related Candidate Gene Variants and Acute Kidney Injury in 2647 Critically Ill Finnish Patients

Acute kidney injury (AKI) is a syndrome with high incidence among the critically ill. Because the clinical variables and currently used biomarkers have failed to predict the individual susceptibility to AKI, candidate gene variants for the trait have been studied. Studies about genetic predisposition to AKI have been mainly underpowered and of moderate quality. We report the association study of 27 genetic variants in a cohort of Finnish critically ill patients, focusing on the replication of associations detected with variants in genes related to inflammation, cell survival, or circulation. In this prospective, observational Finnish Acute Kidney Injury (FINNAKI) study, 2647 patients without chronic kidney disease were genotyped. We defined AKI according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We compared severe AKI (Stages 2 and 3, n = 625) to controls (Stage 0, n = 1582). For genotyping we used iPLEX(TM) Assay (Agena Bioscience). We performed the association analyses with PLINK software, using an additive genetic model in logistic regression. Despite the numerous, although contradictory, studies about association between polymorphisms rs1800629 in TNFA and rs1800896 in IL10 and AKI, we found no association (odds ratios 1.06 (95% CI 0.89-1.28, p = 0.51) and 0.92 (95% CI 0.80-1.05, p = 0.20), respectively). Adjusting for confounders did not change the results. To conclude, we could not confirm the associations reported in previous studies in a cohort of critically ill patients.Peer reviewe

Identification of a Sudden Cardiac Death Susceptibility Locus at 2q24.2 through Genome-Wide Association in European Ancestry Individuals

Sudden cardiac death (SCD) continues to be one of the leading causes of mortality worldwide, with an annual incidence estimated at 250,000–300,000 in the United States and with the vast majority occurring in the setting of coronary disease. We performed a genome-wide association meta-analysis in 1,283 SCD cases and >20,000 control individuals of European ancestry from 5 studies, with follow-up genotyping in up to 3,119 SCD cases and 11,146 controls from 11 European ancestry studies, and identify the BAZ2B locus as associated with SCD (P = 1.8×10−10). The risk allele, while ancestral, has a frequency of ∼1.4%, suggesting strong negative selection and increases risk for SCD by 1.92–fold per allele (95% CI 1.57–2.34). We also tested the role of 49 SNPs previously implicated in modulating electrocardiographic traits (QRS, QT, and RR intervals). Consistent with epidemiological studies showing increased risk of SCD with prolonged QRS/QT intervals, the interval-prolonging alleles are in aggregate associated with increased risk for SCD (P = 0.006)

Heme oxygenase-1 repeat polymorphism in septic acute kidney injury

Acute kidney injury (AKI) is a syndrome that frequently affects the critically ill. Recently, an increased number of dinucleotide repeats in the HMOX1 gene were reported to associate with development of AKI in cardiac surgery. We aimed to test the replicability of this finding in a Finnish cohort of critically ill septic patients. This multicenter study was part of the national FINNAKI study. We genotyped 300 patients with severe AKI (KDIGO 2 or 3) and 353 controls without AKI (KDIGO 0) for the guanine-thymine (GTn) repeat in the promoter region of the HMOX1 gene. The allele calling was based on the number of repeats, the cut off being 27 repeats in the S-L (short to long) classification, and 27 and 34 repeats for the S-M-L2 (short to medium to very long) classification. The plasma concentrations of heme oxygenase-1 (HO-1) enzyme were measured on admission. The allele distribution in our patients was similar to that published previously, with peaks at 23 and 30 repeats. The S-allele increases AKI risk. An adjusted OR was 1.30 for each S-allele in an additive genetic model (95% CI 1.01-1.66; p = 0.041). Alleles with a repeat number greater than 34 were significantly associated with lower HO-1 concentration (p<0.001). In septic patients, we report an association between a short repeat in HMOX1 and AKI risk

Hypothermia and rewarming induce gene expression and multiplication of cells in healthy rat prostate tissue.

Prostate cancer has been extensively studied, but cellular stress responses in healthy prostate tissue are rarely investigated. Hypothermia is known to cause alterations in mRNA and protein expressions and stability. The aim of this study was to use normal rat prostate as a model in order to find out consequences of cold exposure and rewarming on the expressions of genes which are either members or functionally/structurally related to erythroblastic leukemia viral oncogene B (ErbB) signaling pathway. Relative mRNA expressions of amphiregulin (AMR), cyclin D1 (CyD1), cyclin-dependent kinase inhibitor 1A (p21), transmembrane form of the prostatic acid phosphatase (PAcP), thrombomodulin (TM) and heat shock transcription factor 1 (HSF1) in rat ventral prostate were quantified in mild (2 or 4.5 h at room temperature) and severe (2 or 4.5 h at +10°C) hypothermia and in rewarming after cold exposure (2 h at +10°C followed by 2 h at room temperature or 3 h at +28°C). AMR protein level, apoptotic Bcl-2 associated X protein to B-cell CLL/lymphoma 2 (Bax/Bcl-2) mRNA ratio and proliferative index Ki-67 were determined. 4.5-h mild hypothermia, 2-h severe hypothermia and rewarming increased expression of all these genes. Elevated proliferation index Ki-67 could be seen in 2-h severe hypothermia, and the proliferation index had its highest value in longer rewarming with totally recovered normal body temperature. Pro-apoptotic tendency could be seen in 2-h mild hypothermia while anti-apoptosis was predominant in 4.5-h mild hypothermia and in shorter rewarming with only partly recovered body temperature. Hypothermia and following rewarming promote the proliferation of cells in healthy rat prostate tissue possibly via ErbB signaling pathway

EGFR-ligand AMR protein expression and proliferative Ki-67 index in rat ventral prostate.

<p>EGFR-ligand AMR protein expression and proliferative Ki-67 index in rat ventral prostate.</p

Relative mRNA expressions of <i>AMR</i>, <i>PAcP</i>, <i>TM</i>, <i>CyD</i>1, <i>p21</i> and <i>HSF1</i> in rat ventral prostate.

<p>Relative mRNA expressions of <i>AMR</i>, <i>PAcP</i>, <i>TM</i>, <i>CyD</i>1, <i>p21</i> and <i>HSF1</i> in rat ventral prostate.</p

<i>Bax</i> mRNA to <i>Bcl-2</i> mRNA ratios in rat ventral prostate.

<p><i>Bax/Bcl-2</i> mRNA ratio in MH1 correlated negatively with <i>AMR</i> mRNA (<i>r</i> = -0.848, <i>p</i> = 0.033).</p

Statistically significant differences of relative mRNA expressions between control and other groups.

<p>Statistically significant differences of relative mRNA expressions between control and other groups.</p