Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Essential hypertension (EH) is a multifactorial disorder determined by the interaction of environmental and genetic factors. EH patients' responses to these factors may vary, depending on differences in their genes that determine the physiological systems that mediate the response. The purpose of this investigation was to clarify the contributions of genetic background and lifestyle to EH through an association study using some common single nucleotide polymorphisms (SNPs) that should have functional effects on EH phenotypes. We studied the associations between common SNPs of some causal genes related to EH and lifestyle in a Japanese population. The variants of the causal genes were selected based on their functions, including: obesity (adrenergic, beta-3-, receptor: ADRB3), alcohol consumption (aldehyde dehydrogenase 2: ALDH2), water-electrolyte metabolism (guanine nucleotide binding protein [G protein], beta polypeptide 3: GNB3), glycometabolism (peroxisome proliferator-activated receptor gamma: PPARG), lipometabolism (cholesteryl ester transfer protein, plasma: CETP), atherosclerosis (5,10-methylenetetrahydrofolate reductase [NADPH]: MTHFR), and cellular behavior (gap junction protein, alpha 4, 37 kD: GJA4). Case-control association analysis showed a significant association between EH and both the ALDH2 (Lys487Glu) and GNB3 (C825T) variants. Logistic regression analysis indicated that body mass index (BMI) is an important risk factor for EH, and that the GG (Glu/Glu) genotype of ALDH2 was an independent risk factor for EH overall and especially for EH in males. There was no interaction between the ALDH2 genotype and alcohol consumption overall or in male subjects. Our results suggest that the ALDH2 genotype is associated with EH independently of alcohol consumption.
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PMID:Common single nucleotide polymorphisms in Japanese patients with essential hypertension: aldehyde dehydrogenase 2 gene as a risk factor independent of alcohol consumption. 1778 25

The Pro12Ala polymorphism of peroxisome proliferator-activated receptor-gamma (PPARG; NCBI dbSNP rs1801282) has been associated with preservation of cognitive function, decreased risk of diabetes, and increased risk of obesity. We attempted to replicate these associations, testing cognitive function and lifetime cognitive change in 519 participants who took the same cognitive test at ages 11 and 79 years. Scores were also available for other cognitive tests at age 79 years, along with history of diabetes, current Body Mass Index (BMI), and other disease and demographic variables. Pro12Ala carrier status was not directly associated with diabetes history or BMI. In carriers who contracted diabetes despite carrying the protective allele, cognitive decline as measured by one test was significantly greater than in other groups. Only six individuals fell into this group; the other cognitive tests did not show this effect. This sample did not replicate the direct association of the PPARG Pro12Ala allele with diabetes status or preserved cognitive function. The data did suggest that risk of cognitive decline is greater when Pro12Ala carriers contract diabetes.
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PMID:PPARG Pro12Ala genotype and risk of cognitive decline in elders? Maybe with diabetes. 1828 41

Chromosomal localization of nine porcine genes encoding transcription factors involved in adipogenesis was determined. BAC clones harboring sequences of selected genes CEBPA (SSC6q12), CEBPB (SSC17q23), CEBPD (SSC4q15), CEBPG (SSC6q12), PPARG (SSC13q24), SREBF1 (SSC10q17), DDIT3 (SSC12q15), GATA2 (SSC13q24 -->q31) and GATA3 (SSC5p12) were mapped by FISH. The positions of these genes in the human and pig genomes were compared. A potential role of the genes encoding adipogenesis factors as candidate genes for fatness traits as well as obesity-related phenotypes is discussed.
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PMID:Chromosomal localization of nine porcine genes encoding transcription factors involved in adipogenesis. 1854 26

Type 2 diabetes is one of the fastest growing public health problems worldwide. Both environmental (e.g. physical activity, obesity, and diet) and genetic factors are involved in the development of type 2 diabetes. The associations between physical activity and diabetes risk have been assessed by a number of prospective studies and clinical trials. The results from these studies consistently indicate that the regular physical activity during occupation, commuting, leisure time or daily life reduces the risk of type 2 diabetes by 15-60%; and lifestyle intervention, including counselling for physical activity, nutrition, and body weight, can reduce the risk of type 2 diabetes by 40-60% among adults with impaired glucose tolerance and by about 20% among general individuals. In the past decade, studies using traditional linkage analysis and candidate-gene association approach have found dozens of genes harboring common variants that were related to the common-form type 2 diabetes. However, most reported associations are lack of reproducibility, except TCF7L2, PPARG, CAPN10, and KCNJ11. Since 2007, seven genome-wide association (GWA) studies emerged to generate a list of new diabetes genes. The genetic effects are largely of moderate size. These findings provide novel insight into the diabetes etiology and pave new avenue for predicting the disease risk using genetic information. In addition, data especially those from intervention trials display preliminary but promising evidence that the genetic variants might interact with physical activity in predisposing to type 2 diabetes. The gene-environment interactions merit extensive exploration in large, prospective studies.
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PMID:Genes, environment, and interactions in prevention of type 2 diabetes: a focus on physical activity and lifestyle changes. 1878 59

The LPIN1 gene, encoding lipin-1 protein, plays critical roles in adipocyte differentiation and lipid metabolism. This study aimed to analyze the association of LPIN1 mRNA levels in human adipose tissue with metabolic phenotypes. We also examined the association of LPIN1 genetic variation with type 2 diabetes and related metabolic phenotypes in the Chinese population. The relative LPIN1 mRNA levels were measured in abdominal visceral (VAT) and subcutaneous adipose tissue (SAT) obtained from 102 nondiabetic Chinese females. Seven single-nucleotide polymorphisms (SNPs) spanning from the 5'-upstream region to the 3'-end of the LPIN1 gene were genotyped in 1,520 Chinese (760 type 2 diabetic cases and 760 controls). LPIN1 mRNA levels in VAT were negatively correlated with BMI (r = -0.21, P = 0.03), body fat percentage (r = -0.22, P = 0.02), plasma triglycerides levels (r = -0.21, P = 0.03), and plasma leptin levels (r = -0.63, P = 0.0002). LPIN1 mRNA levels were positively correlated with PPARG and ADIPOQ mRNA levels in both VAT and SAT. No single SNP of the LPIN1 gene was associated with type 2 diabetes in our population. One rare haplotype showed a significant association with type 2 diabetes (odds ratio (OR), 4.35; 95% confidence interval, 1.86-11.75; P = 4 x 10(-4)). No SNP or haplotype of the LPIN1 gene was associated with quantitative metabolic traits in the nondiabetic subjects. The results confirmed the association of LPIN1 gene expression in adipose tissue with lower adiposity and favorable metabolic profiles in the Chinese population. However, the LPIN1 gene seemed not to be a major susceptibility gene for type 2 diabetes or related metabolic phenotypes in the Chinese population.
Obesity (Silver Spring) 2010 Jan
PMID:The associations of LPIN1 gene expression in adipose tissue with metabolic phenotypes in the Chinese population. 1954 9

We have examined the association of 14 tagging single nucleotide polymorphisms (tagSNPs) in peroxisome proliferator activated receptor-gamma transcripts 1 and 2 (PPARG1 and 2) and 5 tagSNPs in adiponectin (ADIPOQ) genes for their effect on type 2 diabetes mellitus (T2D) risk in Asian Indian Sikhs. A total of 554 T2D cases and 527 normoglycemic controls were examined for association with T2D and other subphenotypes of T2D. With the exception of a strong association of PPARG2/Pro12Ala with T2D (odds ratio, 0.13; 95% confidence interval, 0.03-0.56; P = .0007), no other tagSNP in the PPARG locus revealed any significant association with T2D in this population. Similarly, none of the tagSNPs in the ADIPOQ gene was associated with T2D susceptibility in single-site analysis. However, haplotype analysis provided strong evidence of association of these loci with T2D. Three-site haplotype analysis in the PPARG locus using the 2 marginally associated SNPs (P/rs11715073 and P/rs3892175) in combination with Pro12 Ala (P/rs1801282) revealed a strong association of 1 "risk" (CGC) (P = .003, permutation P = .015) and 1 "protective" (CAC) (P = .001, permutation P = .005) haplotype associated with T2D. However, the major effect still appears to be driven by Pro12Ala, as the association of these haplotypes did not remain significant when analyzed conditional upon Pro12Ala (P = .262). In addition, 2-site haplotype analysis in the ADIPOQ locus using only 2 marginally associated SNPs (AD/rs182052 and AD/rs7649121) revealed a significant protective association of the GA haplotype with T2D (P = .009, permutation P = .026). Multiple linear regression analysis also revealed significant association of an ADIPOQ variant (AD/rs12495941) with total body weight (P = .010), waist (P = .024), and hip (P = .021), although these associations were not significant after adjusting for multiple testing. Our new findings strongly suggest that the genetic variation in PPARG and ADIPOQ loci could contribute to the risk for the development of T2D in Indian Sikhs. Identification of causal SNPs in these important biological and positional candidate genes would help determine the true physiologic significance of these loci in T2D and obesity.
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PMID:PPARG and ADIPOQ gene polymorphisms increase type 2 diabetes mellitus risk in Asian Indian Sikhs: Pro12Ala still remains as the strongest predictor. 1984 76

Obesity is a global and growing problem. The detrimental health consequences of obesity are significant and include co-morbidities such as diabetes, cancer and coronary heart disease. The marked rise in obesity observed over the last three decades suggests that behavioural and environmental factors underpin the chronic mismatch between energy intake and energy expenditure. However, not all individuals become obese, suggesting that there is considerable variation in responsiveness to 'obesogenic' environments. Some individuals defend easily against a propensity to accumulate fat mass and become overweight whilst others are predisposed to gain weight, possibly as a function of genotype. The genetic contribution to obesity is well established. Common obesity is polygenic, involving complex gene-gene and gene-environment interactions, and it is these interactions that produce the multi-factorial obese phenotypes. Candidate gene variants for polygenic obesity appear to disrupt pathways involved in the regulation of energy intake and expenditure and include adrenergic receptors, uncoupling proteins, PPARG, POMC, MC4R and a set of single nucleotide polymorphisms in the FTO locus. Notably, the FTO gene is the most robust gene for common obesity characterised to date, and recent data shows that the FTO locus seems to confer risk of obesity through increasing energy intake and reduced satiety. Gene variants involved in pathways regulating addiction and reward behaviours may also play a role in predisposition to obesity. Understanding the routes through which the genotype is expressed will ultimately provide opportunities for developing strategies to intervene, as the interaction between genotype and environment is potentially modifiable through behaviour change.
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PMID:Gene-environment interactions in obesity. 1995 87

PPARgamma plays a key role in the regulation of adipocyte differentiation and energy balance. The polymorphism in human PPARG gene resulting in the substitution of Pro12 to Ala in the PPARgamma2 isoform has been established as conferring anti-diabetic and anti-obesity effects, especially in the conditions such as westernized lifestyle with high levels of endogenous ligands for PPARgamma. Thus this is a good example of gene-environment interaction in human diseases. Since this polymorphism is predicted to generate a less active transcription factor, several different phases for metabolism in vivo with regard to PPARgamma activities are assumed.
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PMID:[PPARG gene polymorphism and disease susceptibility]. 2015 84

The phenotypic stability of somatic cells is essential for the maintenance of both structural and functional organ integrity of the adult human body. Deregulated cell plasticity could result in the development of debilitating diseases such as cancer, fibrosis, atherosclerosis, obesity, and type 2 diabetes. We have previously demonstrated that a nonsense mutation in the NPC2 gene, which encodes ubiquitous, highly conserved, secretory protein with unknown function, leads to activation of human skin fibroblasts. The activated fibroblasts, also known as myofibroblasts, have the properties of mesenchymal stem cells and are able to differentiate along the mesodermal and endodermal lineages. Here we show that NPC2-null, but not the normal skin fibroblasts, possess characteristics of adipogenic progenitors as demonstrated by their specific gene expression pattern as well as the ability for efficient differentiation into white adipocytes. The presence of NPC2 in mature white adipocytes was also necessary for their maintenance because silencing NPC2 in differentiated cells by siRNA stimulated PPARG expression, which was followed by a shift toward a more favorable, brown adipocyte-like metabolic state characterized by up-regulated lipolysis and increased insulin sensitivity. It appears that NPC2 controls both the adipogenesis and the metabolic state of mature white adipocytes through a common mechanism that is linked to activation of FGFR2 that could be followed by induction of PPARG expression. Altogether, the current study highlights NPC2 as a novel intracrine/autocrine factor that controls adipocyte differentiation and function as well as potential therapeutic target for the treatment of type 2 diabetes and related metabolic disorders.
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PMID:Somatic cell plasticity and Niemann-pick type C2 protein: adipocyte differentiation and function. 2065 Aug 96

Adipose tissue morphology and release of free fatty acids, as well as peptide hormones, are believed to contribute to obesity and related metabolic disorders. These adipose tissue phenotypes are influenced by adiposity, but there is also a strong hereditary impact. Polymorphisms in numerous adipose-expressed genes have been evaluated for association with adipocyte and clinical phenotypes. In our opinion, some results are convincing. Thus ADRB2 and GPR74 genes are associated with adipocyte lipolysis, GPR74 also with BMI; PPARG and SREBP1, which promote adipogenesis and lipid storage, are associated with T2D and possible adiposity; ADIPOQ and ARL15 are associated with circulating levels of adiponectin, ARL15 also with coronary heart disease. We anticipate that the use of complementary approaches such as expression profiling and RNAi screening, and studies of additional levels of gene regulation, that is, miRNA and epigenetics, will be important to unravel the genetics of adipose tissue function.
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PMID:Genetics of adipose tissue biology. 2103 22


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