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Background: Recent efforts have been made to link complex human traits and disease susceptibility to DNA copy numbers. The leptin receptor (LEPR) has been implicated in obesity and diabetes. Mutations and genetic variations of LEPR gene have been discovered in rodents and humans. However, the association of DNA copy number variations at the LEPR gene locus with human complex diseases has not been reported. In an attempt to study DNA copy number variations associated with metabolic traits and type 2 diabetes mellitus (T2DM), we targeted the LEPR gene locus in DNA copy number analyses. Results: We identified DNA copy number variations at the LEPR gene locus among a Korean population using genome-wide SNP chip data, and then quantified copy numbers of the E2 DNA sequence in the first two exons overlapped between LEPR and LEPROT genes by the quantitative multiplex PCR of short fluorescent fragment (QMPSF) method. Among the non-diabetic subjects (n = 1,067), lower E2 DNA copy numbers were associated with higher fasting glucose levels in men (p = 1.24 × 10-7) and women (p = 9.45 × 10-5), as well as higher total cholesterol levels in men (p = 9.96 × 10-7). In addition, the significant association between lower E2 DNA copy numbers and lower level of postprandial 2hr insulin was evident only in non-diabetic women, whereas some obesity-related phenotypes and total cholesterol level exhibited significant associations only in non-diabetic men. Logistic regression analysis indicated that lower E2 DNA copy numbers were associated with T2DM (odds ratio, 1.92; 95% CI, 1.26∼2.96; p < 0.003) in our nested case-control study. Interestingly, the E2 DNA copy number exhibited a negative correlation with LEPR gene expression, but a positive correlation with LEPROT gene expression. Conclusions: This work suggests that a structural variation at the LEPR gene locus is functionally associated with complex metabolic traits and the risk of T2DM. [ABSTRACT FROM AUTHOR]

Much research evidence supports the hypothesis that chronic, low-grade inflammation related to innate immunity may play an important role in the pathophysiology of type 2 diabetes mellitus (T2DM). Runt-related transcription factor 2 (RUNX2; MIM# 600211) acts as a scaffold that controls the integration, organization, and assembly of nucleic acids. To examine whether the novel promoter variant in RUNX2 is associated with the risk of T2DM and related phenotypes, RUNX2-742G > T was genotyped in 378 T2DM patients and 382 normal controls recruited in the Korean T2DM Study. Statistical analysis revealed that RUNX2-742G > T was associated with serum triglyceride level (TG) in nondiabetic controls, although it was not associated with the risk of T2DM. Individuals who carry T/T, T/G, and G/G genotypes had the highest (2.061 ± 020), intermediate (2.01 ± 0.19), and the lowest (1.97 + 0.18) levels of log [TG (mmol/l)] (P = 0.007), respectively. Our data on this important variant of orkuO suggest that lipid metabolism might be affected by genetic polymorphisms in the promoter region. [ABSTRACT FROM AUTHOR]

Chronic viral infection is implicated in cognitive decline and Alzheimer's disease (AD). Our goal was to identify biomarkers for the development of amnestic mild cognitive impairment (aMCI) from cognitively normal state. To accomplish this, we analyzed plasma IgG levels against Epstein-Barr virus (EBV) and herpes simplex virus 1 (HSV-1) in study subjects with incident aMCI (Converter) and normal cognitive function (NC Control) who did or did not convert from cognitively normal state to aMCI during the 2-year follow-up period, respectively. The Converter group exhibited elevated levels of anti-EBV IgG antibodies in the post-follow-up phase (aMCI state) compared to the pre-follow-up phase (cognitively normal state), but not the NC Control group. In contrast, the total IgG level was not significantly changed over the follow-up period. Moreover, elevated anti-EBV IgG levels were significantly associated with CDR scales and total CERAD scores in the Converter group. These results suggest that EBV infection or its related host immune response is linked to cognitive decline. Thus, an EBV antibody level may be used as a potential biomarker for assessing the risk of aMCI development, implying a role for chronic EBV infection in AD pathogenesis. [ABSTRACT FROM AUTHOR]

Glucose ingestion-induced hyperglycemia has been known to induce inflammation, which is related to the pathogenesis of diabetic complications. To examine acute gene expression responses to physiological oral glucose ingestion in human circulating leukocytes, we conducted a microarray study of human circulating leukocytes sampled before, 1 h after, and 2 h after glucose ingestion in community-based participants without previous histories of diabetes (n = 60). Ingestion of 75 g glucose successfully induced acute hyperglycemia (glucose concentration 91.6 ± 5.3 mg/dl for fasting and 180.7 ± 48.5 mg/dl for 1 h after glucose ingestion). Oral glucose ingestion significantly increased the expressions of 23 genes and decreased the expressions of 13 genes [false discovery rate (FDR) P value <0.05]. These genes are significantly involved in immunity by way of natural killer cell-mediated immunity, granulocyte-mediated immunity, and the cytokine-mediated signaling pathway (FDR P value <0.05). The present study demonstrated 36 genes that showed acute gene expression change in human leukocytes within 1 h after glucose ingestion, suggesting that leukocytes participate in the inflammatory process induced by acute hyperglycemia. We believe that these results will provide some basic insight into the role of leukocytes in hyperglycemia-induced inflammation and the pathogenesis of diabetic complications. [ABSTRACT FROM AUTHOR]

Dot blot hybridization of total RNA from normal and bacteria-injected larvae of the dung beetle Copris tripartitus identified 13 cDNA clones that seem to be associated with the immune response. A cDNA encoding a dung beetle homolog of the heat shock protein HSP70 (CTHSP70) was characterized by full-length sequencing and expression pattern analysis. CTHSP70 was upregulated 4 h after bacterial injection, reached maximum level after 8 h, and declined gradually after 16 h. Our data suggest that CTHSP70 and another 12 genes are involved in the anti-microbial defense that is particularly important for dung beetle larvae living in pathogen-rich conditions. [ABSTRACT FROM AUTHOR]

We constructed a full-length cDNA library from diapausing queens of the bumblebee Bombus ignitus. A total of 480 randomly selected clones was sequenced by single-run 5′-end sequencing. Of these, there were 437 high quality clones, 23 poor quality clones and 20 read-fail clones. Each high quality clone sequence was searched against a public protein database. The most frequently found matching genes were ribosomal proteins (12.5%), p10 (3.58%), cytochrome P450 monooxygenase (3.13%) and sensory appendage protein (2.9%). Sequence similarity analysis between bumblebees and other insect species showed that 72 out of 437 (16.5%) bumblebee expressed sequence tags (EST) matched sequences of Apis mellifera, with matches to Drosophila melanogaster (6.6%), Caenorhabditis briggsae (6.2%), Lysiphlebus testaceipes (4.8%), Periplaneta americana (3.7%) and Anopheles gambiae (3.4%) following, suggesting that sequence similarity of bumblebee EST is closest to that of A. mellifera. Functional classification of EST based on Gene Ontology showed that most genes found by sequencing are associated with physiological processes in the bumblebee. The results of sequencing and analysis of our 437 cDNA demonstrated that high-throughput EST sequencing and data analysis are powerful means for identifying novel genes and for expression profiling. Our bumblebee EST collection could be a useful platform for further studies of gene expression in diapausing bumblebees. [ABSTRACT FROM AUTHOR]