Identification of shared genetic susceptibility locus for coronary artery disease, type 2 diabetes and obesity: a meta-analysis of genome-wide studies

<p>Abstract</p> <p>Type 2 diabetes (2DM), obesity, and coronary artery disease (CAD) are frequently coexisted being as key components of metabolic syndrome. Whether there is shared genetic background underlying these diseases remained unclear. We performed a meta-analysis of 35 genome screens for 2DM, 36 for obesity or body mass index (BMI)-defined obesity, and 21 for CAD using genome search meta-analysis (GSMA), which combines linkage results to identify regions with only weak evidence and provide genetic interactions among different diseases. For each study, 120 genomic bins of approximately 30 cM were defined and ranked according to the best linkage evidence within each bin. For each disease, bin 6.2 achieved genomic significanct evidence, and bin 9.3, 10.5, 16.3 reached suggestive level for 2DM. Bin 11.2 and 16.3, and bin 10.5 and 9.3, reached suggestive evidence for obesity and CAD respectively. In pooled all three diseases, bin 9.3 and 6.5 reached genomic significant and suggestive evidence respectively, being relatively much weaker for 2DM/CAD or 2DM/obesity or CAD/obesity. Further, genomewide significant evidence was observed of bin 16.3 and 4.5 for 2DM/obesity, which is decreased when CAD was added. These findings indicated that bin 9.3 and 6.5 are most likely to be shared by 2DM, obesity and CAD. And bin 16.3 and 4.5 are potentially common regions to 2DM and obesity only. The observed shared susceptibility regions imply a partly overlapping genetic aspects of disease development. Fine scanning of these regions will definitely identify more susceptibility genes and causal variants.</p

Stabilized Nanoscale Zerovalent Iron Mediated Cadmium Accumulation and Oxidative Damage of <i>Boehmeria nivea</i> (L.) Gaudich Cultivated in Cadmium Contaminated Sediments

Nanoparticles can be absorbed by plants, but their impacts on phytoremediation are not yet well understood. This study was carried out to determine the impacts of starch stabilized nanoscale zerovalent iron (S-nZVI) on the cadmium (Cd) accumulation and the oxidative stress in <i>Boehmeria nivea</i> (L.) Gaudich (ramie). Plants were cultivated in Cd-contaminated sediments amended with S-nZVI at 100, 500, and 1000 mg/kg, respectively. Results showed that S-nZVI promoted Cd accumulation in ramie seedlings. The subcellular distribution result showed that Cd content in cell wall of plants reduced, and its concentration in cell organelle and soluble fractions increased at S-nZVI treatments, indicating the promotion of Cd entering plant cells by S-nZVI. In addition, the 100 mg/kg S-nZVI alleviated the oxidative damage to ramie under Cd-stress, while 500 and 1000 mg/kg S-nZVI inhibited plant growth and aggravated the oxidative damage to plants. These findings demonstrate that nanoparticles at low concentration can improve the efficiency of phytoremediation. This study herein develops a promising novel technique by the combined use of nanotechnology and phytoremediation in the remediation of heavy metal contaminated sites

MAPKAP1 rs10118570 Polymorphism Is Associated with Anti-Infection and Anti-Hepatic Fibrogenesis in Schistosomiasis Japonica

Chronic infection with Schistosoma japonicum is an important cause of hepatic fibrosis (HF). Human 9q33.3 is one of the most important loci for stress-related diseases. We examined the potential associations of 43 single-nucleotide polymorphisms (SNPs) with S. japonicum infection and HF in epidemic region in China. We identified a SNP (rs10118570 GG in mitogen-activated protein kinase associated protein 1, MAPKAP1) contributes to anti-infection (adjusted OR = 0.35) and anti-fibrogenesis (adjusted RR = 0.44) in the discovery study. Replicative and combined studies showed consistent protective quality for this genotype (replicative: adjusted OR = 0.37 for anti-infection, and adjusted RR = 0.40 for anti-fibrogenesis; Combined: adjusted OR = 0.45 for anti-infection, and adjusted RR = 0.42 for anti-fibrogenesis). Univariate and multivariate analysis in the discovery, replicative and combined studies, suggested that durations (years), splenomegaly, serum ALB and rs10118570 were independent predictors influencing the fibrogenesis. The analysis of gene-gene interaction showed rs10118570 functions independently. We conclude that MAPKAP1 may represent a novel anti-infection and anti-fibrogenesis genomic locus in chronic schistosomiasis japonica. And rs10118570 may be a potential biomarker and target for the treatment of this life-threatening ancient disease

Variables associated with presence or absence of advanced hepatic fibrosis (grade III/IV) in the discovery, replicative and combined cohorts with univariate and multivariate analysis.

<p>(A) Analysis in the discovery cohort. (B) Analysis in the replicative cohort. (C) Analysis in the combined cohort.</p

Association of (A) haplotypes and (B) diplotypes on 9q33.3 with risk of hepatic fibrosis in chronic S. japonicum infected Adults in the discovery study.

<p>Block 1, rs12343206–rs10733669; Block 2, rs11355458–rs17840761–rs17840762–rs391957; Block 3, rs10819146–rs531599; Block 4, rs2454217–rs487914–rs488039. RR, relative risk; CI, confidence interval. Unadjusted RR was calculated using Pearson Chi-square test. Adjusted RR was adjusted for age, gender, smoking, drinking and HBsAg. d, the deleted base.</p

Clinical and laboratory features of the subjects included in the study^*.

<p>*HF, hepatic fibrosis; SD, standard deviation; BMI, body mass index; WBC, white blood cell; HBV, hepatitis B virus; AFP, alpha-fetal protein; T-Bil, total bilirubin; ALB, albumin; ALT, alanine transaminase.</p>†<p>Length of left liver lobe, a longitudinal section at left parasternal line. Length of right liver lobe, anterior axillary view and maximum oblique diameter between front and back sections with inspiration.</p>‡<p>Thickness of spleen from hilum to opposite section. Length of spleen in left oblique view with maximum length in a section through the splenic hilus.</p

Association results of two SNPs with risk of hepatic fibrosis in chronic S. japonicum infected adults in the discovery, replication and combined studies.

<p>Unadjusted RR was calculated using Pearson Chi-square test. Adjusted RR was adjusted for age, gender, smoking, drinking and HBsAg. d, the deleted base.</p

Association results of the two SNPs with risk of <i>S. japonicum</i> infection in the discovery, replicative and combined studies.

<p>Adjusted for age, gender, smoking and drinking.</p><p><i>P</i><1.163×10⁻³ means significant value by Bonferroni correction based on the total number of markers genotyped.</p

Analysis of the statistical interactions between rs10118570 and rs391957 in the discovery, replicative and combined cohorts.

<p>*<i>P</i>_int, <i>P</i> value for the interaction.</p><p><i>P</i>_int<0.0167 means significant value by Bonferroni correction based on the total number of studies.</p

The ultrasonography diagnosis criteria of hepatic fibrosis in schistosomiasis endemic regions in China.

<p>The ultrasonography diagnosis criteria of hepatic fibrosis in schistosomiasis endemic regions in China.</p