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Advancement in genetic variants conferring obesity susceptibility from genome-wide association studies

null

《医学前沿（英文）》 2015年 第9卷 第2期   页码 146-161 doi: 10.1007/s11684-014-0373-8

摘要：

Obesity prevalence has increased in recent years. Lifestyle change fuels obesity, but genetic factors cause more than 50% of average variations in obesity. The advent of genome-wide association studies (GWAS) has hastened the progress of polygenic obesity research. As of this writing, more than 73 obesity susceptibility loci have been identified in ethnic groups through GWAS. The identified loci explain only 2% to 4% of obesity heritability, thereby indicating that a large proportion of loci remain undiscovered. Thus, the next step is to identify and confirm novel loci, which may exhibit smaller effects and lower allele frequencies than established loci. However, achieving these tasks has been difficult for researchers. GWAS help researchers discover the causal loci. Moreover, numerous biological studies have been performed on the polygenic effects on obesity, such as studies on fat mass- and obesity-associated gene (FTO), but the role of these polygenic effects in the mechanism of obesity remains unclear. Thus, obesity-causing variations should be identified, and insights into the biology of polygenic effects on obesity are needed.

关键词： obesity     genetics     genome-wide association studies     body mass index     fat mass- and obesity-associated gene    

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Brown and beige fat: the metabolic function, induction, and therapeutic potential

null

《医学前沿（英文）》 2015年 第9卷 第2期   页码 162-172 doi: 10.1007/s11684-015-0382-2

摘要：

Adipose tissue is an important organ for energy homeostasis. White adipose tissue stores energy in the form of triglycerides, whereas brown adipocytes and recently identified beige adipocytes are specialized in dissipating energy by thermogenesis or contribution to dispose glucose and clear triglycerides in blood. The inverse correlation between the brown adipose tissue activity and body mass suggests its protective role against body fat accumulation. Thus, recruitment and activation of brown or beige adipose tissue become particularly appealing targets for increasing energy expenditure. Angiogenesis and sympathetic nerve signals are the fundamental determinants for brown and beige adipose tissue development, as well as for their metabolic functions. Secretary factors including BMPs can induce the development, the activation of brown or beige adipose tissue, which seem to be promising for therapeutic development.

关键词： brown adipocyte     beige adipocyte     metabolism     obesity    

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Postnatal feeding with high-fat diet induces obesity and precocious puberty in C57BL/6J mouse pups: anovel model of obesity and puberty

null

《医学前沿（英文）》 2017年 第11卷 第2期   页码 266-276 doi: 10.1007/s11684-017-0530-y

摘要：

Childhood obesity and obesity-related metabolic complications are induced by a high-fat postnatal diet. The lack of a suitable animal model, however, remains a considerable challenge in obesity studies. In the current study, we provided high-fat diet (HFD) to dams during lactation and to pups after weaning. We also developed a novel model of C57BL/6J mouse pups with HFD-induced postnatal obesity. Results showed that feeding with HFD induces fat deposition and obesity in pups. Furthermore, HFD more potently increased the body weight (BW) of male than female pups. HFD-fed female pups were obese, underwent precocious puberty, and showed increased kisspeptin expression in the hypothalamus. However, parental obesity and precocious puberty exerted no synergistic effects on the HFD-induced postnatal weight gain and puberty onset of the pups. Interestingly, some HFD-fed litters with normal BW also exhibited precocious puberty. This finding suggested that diet composition but not BW triggers puberty onset. Our model suggests good construction validity of obesity and precocious puberty. Furthermore, our model can also be used to explore the mutual interactions between diet–induced postnatal childhood obesity and puberty.

关键词： postnatal HFD feeding     obesity     kisspeptin     HPG axis     precocious puberty    

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Genome-wide association analysis reveals genetic loci and candidate genes associated with intramuscularfat in Duroc pigs

Xingwang WANG, Rongrong DING, Jianping QUAN, Linxue YANG, Ming YANG, Enqin ZHENG, Dewu LIU, Gengyuan CAI, Zhenfang WU, Jie YANG

《农业科学与工程前沿（英文）》 2017年 第4卷 第3期   页码 335-341 doi: 10.15302/J-FASE-2017152

摘要： Intramuscular fat (IMF) is a major meat-quality trait in pigs. The content of IMF is directly associated with the taste and flavor of pork. As a complex trait, there could be multiple genes affecting IMF content in pork. Genome-wide association study is a powerful tool to detect genomic regions associated with phenotypic variations. The objectives of the present study were to identify or refine the positions of genomic regions affecting IMF, and to characterize candidate genes and pathways that may influence this trait. Of note, we identified a significant region in longissium dorsi muscle in a Duroc pig population for IMF content with PorcineSNP60 v2 BeadChip. This region spans 1.24 Mb on chromosome 8 and had been identified as a quantitative trait locus for IMF in Pietrain, Large White, Landrace, and Leicoma pigs. In this region, eight SNPs were significantly associated with IMF content. Three genes proximal to these significant SNPs were considered candidate genes, including , and . Our results confirm several previous findings and highlight several genes that may contribute to IMF variation in Duroc pigs.

关键词： Duroc pigs     genome-wide association analysis     intramuscular fat    

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Fanconi anemia gene-associated germline predisposition in aplastic anemia and hematologic malignancies

《医学前沿（英文）》 2022年 第16卷 第3期   页码 459-466 doi: 10.1007/s11684-021-0841-x

摘要： Whether Fanconi anemia (FA) heterozygotes are predisposed to bone marrow failure and hematologic neoplasm is a crucial but unsettled issue in cancer prevention and family consulting. We retrospectively analyzed rare possibly significant variations (PSVs) in the five most obligated FA genes, BRCA2, FANCA, FANCC, FANCD2, and FANCG, in 788 patients with aplastic anemia (AA) and hematologic malignancy. Sixty-eight variants were identified in 66 patients (8.38%). FANCA was the most frequently mutated gene (n = 29), followed by BRCA2 (n = 20). Compared with that of the ExAC East Asian dataset, the overall frequency of rare PSVs was higher in our cohort (P = 0.016). BRCA2 PSVs showed higher frequency in acute lymphocytic leukemia (P = 0.038), and FANCA PSVs were significantly enriched in AA and AML subgroups (P = 0.020; P = 0.008). FA-PSV-positive MDS/AML patients had a higher tumor mutation burden, higher rate of cytogenetic abnormalities, less epigenetic regulation, and fewer spliceosome gene mutations than those of FA-PSV-negative MDS/AML patients (P = 0.024, P = 0.029, P = 0.024, and P = 0.013). The overall PSV enrichment in our cohort suggests that heterozygous mutations of FA genes contribute to hematopoietic failure and leukemogenesis.

关键词： Fanconi anemia     aplastic anemia     hematologic malignancy     germline predisposition    

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Early-life famine exposure, adulthood obesity patterns, and risk of low-energy fracture

《医学前沿（英文）》 doi: 10.1007/s11684-023-1023-9

摘要： Malnutrition in early life increases the risk of osteoporosis, but the association of early-life undernutrition combined with adulthood obesity patterns with low-energy fracture remains unknown. This study included 5323 community-dwelling subjects aged ≥40 years from China. Early-life famine exposure was identified based on the participants’ birth dates. General obesity was assessed using the body mass index (BMI), and abdominal obesity was evaluated with the waist-to-hip ratio (WHR). Low-energy fracture was defined as fracture occurring after the age of 40 typically caused by falls from standing height or lower. Compared to the nonexposed group, the group with fetal, childhood, and adolescence famine exposure was associated with an increased risk of fracture in women with odds ratios (ORs) and 95% confidence intervals (CIs) of 3.55 (1.57–8.05), 3.90 (1.57–9.71), and 3.53 (1.05–11.88), respectively, but not in men. Significant interactions were observed between fetal famine exposure and general obesity with fracture among women (P for interaction = 0.0008). Furthermore, compared with the groups with normal BMI and WHR, the group of women who underwent fetal famine exposure and had both general and abdominal obesity had the highest risk of fracture (OR, 95% CI: 3.32, 1.17–9.40). These results indicate that early-life famine exposure interacts with adulthood general obesity and significantly increases the risk of low-energy fracture later in life in women.

关键词： famine     obesity     body mass index     waist-to-hip ratio     low-energy fracture    

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Regulation of exogenous bFGF gene mediated by recombinant adeno-associated virus

Ke SONG, Nianjing RAO, Meiling CHEN, Yingguang CAO

《医学前沿（英文）》 2009年 第3卷 第2期   页码 158-163 doi: 10.1007/s11684-009-0042-5

摘要： The regulatory effect of basic fibroblast growth factor (bFGF) mediated by recombinant adeno-associated virus (AAV) was investigated. Recombinant plasmid pAAV-S3-bFGF, and pSVneo were co-transfected into BHK-21 cells, then the recombinant AAV genome was replicated and packaged with the helper virus HSV1-rc/ΔUL2. The titer of the recombinant rAAV2-tet-off-bFGF was determined by dot-blot assay. MC3T3-E1 cells were infected with rAAV2-tet-off-bFGF. Regulatory effects of Doxycycline (Dox) on bFGF and osteogenic factors were assayed quantitatively by real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. The physical particle titer of rAAV2-tet-off-bFGF successfully constructed was 1.8×10 vector genomes/mL, and the virus could infect MC3T3-E1 cells effectively. In MC3T3-E1 cells treated with Dox, the expression levels of exogenous bFGF and osteogenic factors declined to varying degrees. It was concluded that rAAV2-tet-off-bFGF could infect MC3T3 cells efficiently, and this recombinant system could be regulated successfully by Dox .

关键词： tetracycline regulatory system     adeno-associated virus     basic fibroblast growth factor     gene regulation    

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Analyzing the distinguishing factors that affect childhood obesity in South Korea

So Jung Yang, Hun-Sung Kim, Kun-Ho Yoon

《医学前沿（英文）》 2018年 第12卷 第6期   页码 707-716 doi: 10.1007/s11684-018-0660-x

摘要：

Understanding obesity in children is crucial because it can lead to adulthood obesity and result in fatal chronic diseases. Distinctive factors associated with obesity in adults have been described, but distinctive factors related to children remain unclear. We analyzed the correlation between the percentage of body mass index and lifestyle habits by conducting surveys on physical, nutritional, and psychological factors, and we used annual physical examination data to compare different traits among elementary school students (n = 197) and middle school students (n = 461). Our study revealed that the computing hours in elementary school students with overweight and obesity were significantly correlated with the percentage of body mass index (r = 0.29 on school days and r = 0.35 on days off, all P<0.05). No statistically significant difference was found (all P>0.05) in the computing hours of middle school students with overweight and obesity. Childhood obesity can cause depression and reduce children’s quality of life because of their distorted body perception. In conclusion, physical factors directly affecting childhood obesity and psychological and environmental factors surrounding a child should be considered.

关键词： screen time     quality of life     eating habits     childhood obesity     percentage of body mass index    

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Multiple effects of grape seed polyphenolics to prevent metabolic diseases

Torey ARVIK, Hyunsook KIM, James SEIBER, Wallace YOKOYAMA

《农业科学与工程前沿（英文）》 2018年 第5卷 第3期   页码 351-361 doi: 10.15302/J-FASE-2018235

摘要：

Obesity is increasing in developing countries. Population studies show a relationship between affluence and obesity. Changing food intake patterns with affluence such as preference for foods with less astringent polyphenolic compounds and dietary fibers may increase risk of metabolic dysfunctions due to caloric imbalance. Animal models of obesity consistently show that grape seed procyanidins prevent increases in body and abdo- minal adipose weight gain, plasma cholesterol, liver weight gain and inflammation in animals on high fat diets. The mechanisms are not clear because the oral intake of procyanidins results in pleiotropic interactions with proteins in the mouth, stomach, small intestine, cecum and colon that affect the rate of digestion of bioavailability of macronutrients, sterols, and dietary fiber. Procyanidins also bind bile acids and reduce intestinal permeability to inflammatory bacterial cell wall fragment. Procyanidins are not degraded or metabolized until reaching the lower gut where they can be metabolized into phenolic acids by gut bacteria. While they are metabolized by gut bacteria, they also alter total numbers and distribution of phyla and species of gut bacteria. Gut bacteria are recognized as significant contributors to obesity and obesity related metabolic diseases. The review examines the different pleiotropic effects of grape seed procyanidins that have a significant effect on metabolic disease in animal models of obesity.

关键词： grape seed     obesity     procyanidins     high fat     microbiota     animal models    

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Bioinformatic exploration of MTA1-regulated gene networks in colon cancer

null

《医学前沿（英文）》 2016年 第10卷 第2期   页码 178-182 doi: 10.1007/s11684-016-0442-2

摘要：

Metastasis-associated gene 1 (MTA1) controls a series of biological processes in tumor progression. Tumor progression is a complex process regulated by a gene network. The global cancer gene regulatory network must be analyzed to determine the position of MTA1 in the molecular network and its cooperative genes by further exploring the biological functions of this gene. We used TCGA data sets and GeneCards database to screen MTA1-related genes. GO and KEGG pathway analyses were conducted with DAVID and gene network analysis via STRING and Cytoscape. Results showed that in the development of colon cancer, MTA1 is linked to certain signal pathways, such as Wnt/Notch/nucleotide excision repair pathways. The findings also suggested that MTA1 demonstrates the closest relationship in a coregulation process with the key molecules AKT1, EP300, CREBBP, SMARCA4, RHOA, and CAD. These results lead MTA1 exploration to an in-depth investigation in different directions, such as Wnt, Notch, and DNA repair.

关键词： metastasis-associated gene 1     colon cancer     bioinformatics    

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Expression and bioinformatic analysis of lymphoma-associated novel gene KIAA0372

BAI Xiangyang, TANG Duozhuang, ZHU Tao, SUN Lishi, YAN Lingling, LU Yunping, ZHOU Jianfeng, MA Ding

《医学前沿（英文）》 2007年 第1卷 第1期   页码 93-98 doi: 10.1007/s11684-007-0018-2

摘要： The purpose of this study was to explore the differentially expressed genes in lymph-node cells (LNC) of lymphomas and reactive lymph node hyperplasia, and to perform an initial bioinformatic analysis on a novel gene, KIAA0372, which is highly expressed in the LNC of lymphomas. mRNA extracted from LNC of lymphomas and reactive lymph node hyperplasia were respectively marked with biotin and hybridized with Gene Expression Chips, resulting in differentially expressed genes. Initial bioinformatic analysis was then performed on a novel gene named KIAA0372, whose function has not yet been explored. Its structure and genomic location, its product s physical and chemical properties, subcellular localization and functional domains, were also predicted. Further, a systematic evolution analysis was performed on similar proteins from among several species. Using Gene Expression Chips, many differentially expressed genes were uncovered. Efficient bioinformatic analysis has fundamentally determined that KIAA0372 is an extracellular protein which may be involved in TGF-β signaling. Microarray is an efficient and high throughput strategy for detection of differentially expressed genes. And KIAA0372 is thought to be a potential target for tumor research using bioinformatic analysis.

关键词： bioinformatic analysis     functional     KIAA0372     detection     Microarray    

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Identification of variants associated with sporadic thoracic aortic dissection: a case--control study

《医学前沿（英文）》 2021年 第15卷 第3期   页码 438-447 doi: 10.1007/s11684-020-0826-1

摘要： Thoracic aortic dissection (TAD) without familial clustering or syndromic features is known as sporadic TAD (STAD). So far, the genetic basis of STAD remains unknown. Whole exome sequencing was performed in 223 STAD patients and 414 healthy controls from the Chinese Han population (N = 637). After population structure and genetic relationship and ancestry analyses, we used the optimal sequence kernel association test to identify the candidate genes or variants of STAD. We found that COL3A1 was significantly relevant to STAD (P = 7.35 × 10−6) after 10 000 times permutation test (P = 2.49 × 10−3). Moreover, another independent cohort, including 423 cases and 734 non-STAD subjects (N = 1157), replicated our results (P = 0.021). Further bioinformatics analysis showed that COL3A1 was highly expressed in dissected aortic tissues, and its expression was related to the extracellular matrix (ECM) pathway. Our study identified a profile of known heritable TAD genes in the Chinese STAD population and found that COL3A1 could increase the risk of STAD through the ECM pathway. We wanted to expand the knowledge of the genetic basis and pathology of STAD, which may further help in providing better genetic counseling to the patients.

关键词： sporadic thoracic aortic dissection     exome sequencing     gene COL3A1     case–control study     extracellular matrix    

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Inhibition of TNF-alpha secretion from peripheral blood monocular cells by triptolid is associated withTNF-alpha-308 gene polymorphisms in rheumatoid arthritis patients

Xiu-Liang TAO MM, Sheng-Hao TU MD, Ri-Bo XIONG MM, Yong-Hong HU BM,

《医学前沿（英文）》 2010年 第4卷 第2期   页码 220-224 doi: 10.1007/s11684-010-0025-6

摘要： This study examined the inhibitory effect of triptolid (TP) on tumor necrosis factor-α (TNF-α) secreted from peripheral blood monocular cells (PBMCs) and the association of the inhibitory effect with TNF-α-308 gene polymorphisms in rheumatoid arthritis (RA) patients. Gene polymorphism at A-G site 308 in the promoter region of TNF-α gene was detected in 42 RA patients by using allele specific polymerase chain reaction (AS-PCR) assay. PBMCs were harvested from these patients and treated first with lipopolysaccharides (LPS) and then with different doses of TP (1, 5.4 and 15 ng/mL). The TNF-α level in the supernatants was measured by enzyme-linked immunosorbent assay (ELISA). The results showed that TNF-α level in the supernatants of TP (1 ng/mL)-treated PBMCs was decreased by 3.80% and 4.91%, respectively, in the patients with AA and AG genotypes, when compared with those treated with LPS alone (>0.05). Moreover, the TNF-α level in the patients with GG genotype was reduced by 20.74% (<0.05). When PBMCs were treated with TP at 5.4 ng/mL, TNF-α levels in the patients with AA, AG, and GG genotypes were decreased by 20.42%, 34.73%, and 41.69%, respectively (<0.05). The TNF-α level was slightly higher in the PBMCs treated with 15 ng/mL of TP than those in the two TP groups in the patients carrying AA, AG, and GG genotypes (>0.05). It was concluded that gene polymorphism at TNF-α-308 sites may relate to the secretion of TNF-α in RA patients. TP has different inhibitory effects on the secretion of TNF-α in the patients harboring different genotypes, which may be one of the reasons for individual variation in response to TP.

关键词： arthritis     rheumatoid     molonuclear cells     tumor necrosis factor     gene polymorphisms     triptolid    

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Haploinsufficiency of Lipin3 leads to hypertriglyceridemia and obesity by disrupting the expression and

《医学前沿（英文）》 doi: 10.1007/s11684-023-1003-0

摘要： Lipin proteins including Lipin 1–3 act as transcriptional co-activators and phosphatidic acid phosphohydrolase enzymes, which play crucial roles in lipid metabolism. However, little is known about the function of Lipin3 in triglyceride (TG) metabolism. Here, we identified a novel mutation (NM_001301860: p.1835A>T/p.D612V) of Lipin3 in a large family with hypertriglyceridemia (HTG) and obesity through whole-exome sequencing and Sanger sequencing. Functional studies revealed that the novel variant altered the half-life and stability of the Lipin3 protein. Hence, we generated Lipin3 heterozygous knockout (Lipin3-heKO) mice and cultured primary hepatocytes to explore the pathophysiological roles of Lipin3 in TG metabolism. We found that Lipin3-heKO mice exhibited obvious obesity, HTG, and non-alcoholic fatty liver disorder. Mechanistic study demonstrated that the haploinsufficiency of Lipin3 in primary hepatocytes may induce the overexpression and abnormal distribution of Lipin1 in cytosol and nucleoplasm. The increased expression of Lipin1 in cytosol may contribute to TG anabolism, and the decreased Lipin1 in nucleoplasm can reduce PGC1α, further leading to mitochondrial dysfunction and reduced TG catabolism. Our study suggested that Lipin3 was a novel disease-causing gene inducing obesity and HTG. We also established a relationship between Lipin3 and mitochondrial dysfunction.

关键词： Lipin3     Lipin1     hypertriglyceridemia     obesity     mitochondrial dysfunction    

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Cyclooxygenase-2 gene-1195G/A genotype is associated with the risk of HBV-induced HCC: A case-control

Li-Feng LIU MD, PhD, Qiong CHEN MD, PhD, Ying CHANG MD, PhD, Ju-Sheng LIN MD, PhD, Jin-Liang ZHANG MM,

《医学前沿（英文）》 2010年 第4卷 第1期   页码 90-95 doi: 10.1007/s11684-010-0021-x

摘要： This study aimed to identify functional single nucleotide polymorphisms in the cyclooxygenase-2 gene promoter and evaluate their effects on the risk of primary hepatocellular carcinoma (HCC) with hepatitis B virus (HBV) infection. We conducted a population-based, case-control study enrolling 630 Han Chinese people in Hubei province. Subjects included primary HCC patients with HBV infection (=210), chronic hepatitis B cases (=210) and healthy Han Chinese (=210). -1195G/A polymorphism was analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequencing analysis. We found-1195A allele carriers had a higher risk of HCC with HBV infection (OR, 0.72; 95% CI, 0.548–0.946). The-1195A allele might be used as a marker in screening individuals at high risk of HCC with HBV infection.

关键词： cyclooxygenase-2 gene     single nucleotide polymorphisms     susceptibility     primary hepatocellular carcinoma     hepatitis B virus infection    

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标题 作者 时间 类型 操作

Advancement in genetic variants conferring obesity susceptibility from genome-wide association studies

null

期刊论文

Brown and beige fat: the metabolic function, induction, and therapeutic potential

null

期刊论文

Postnatal feeding with high-fat diet induces obesity and precocious puberty in C57BL/6J mouse pups: anovel model of obesity and puberty

null

期刊论文

Genome-wide association analysis reveals genetic loci and candidate genes associated with intramuscularfat in Duroc pigs

Xingwang WANG, Rongrong DING, Jianping QUAN, Linxue YANG, Ming YANG, Enqin ZHENG, Dewu LIU, Gengyuan CAI, Zhenfang WU, Jie YANG

期刊论文

Fanconi anemia gene-associated germline predisposition in aplastic anemia and hematologic malignancies

期刊论文

Early-life famine exposure, adulthood obesity patterns, and risk of low-energy fracture

期刊论文

Regulation of exogenous bFGF gene mediated by recombinant adeno-associated virus

Ke SONG, Nianjing RAO, Meiling CHEN, Yingguang CAO

期刊论文

Analyzing the distinguishing factors that affect childhood obesity in South Korea

So Jung Yang, Hun-Sung Kim, Kun-Ho Yoon

期刊论文

Multiple effects of grape seed polyphenolics to prevent metabolic diseases

Torey ARVIK, Hyunsook KIM, James SEIBER, Wallace YOKOYAMA

期刊论文

Bioinformatic exploration of MTA1-regulated gene networks in colon cancer

null

期刊论文

Expression and bioinformatic analysis of lymphoma-associated novel gene KIAA0372

BAI Xiangyang, TANG Duozhuang, ZHU Tao, SUN Lishi, YAN Lingling, LU Yunping, ZHOU Jianfeng, MA Ding

期刊论文

Identification of variants associated with sporadic thoracic aortic dissection: a case--control study

期刊论文

Inhibition of TNF-alpha secretion from peripheral blood monocular cells by triptolid is associated withTNF-alpha-308 gene polymorphisms in rheumatoid arthritis patients

Xiu-Liang TAO MM, Sheng-Hao TU MD, Ri-Bo XIONG MM, Yong-Hong HU BM,

期刊论文

Haploinsufficiency of Lipin3 leads to hypertriglyceridemia and obesity by disrupting the expression and

期刊论文

Cyclooxygenase-2 gene-1195G/A genotype is associated with the risk of HBV-induced HCC: A case-control

Li-Feng LIU MD, PhD, Qiong CHEN MD, PhD, Ying CHANG MD, PhD, Ju-Sheng LIN MD, PhD, Jin-Liang ZHANG MM,

期刊论文