NAFLD Susceptibility Genes and Their Association with Type 2 Diabetes and Obesity in a New Mexico Population

Garner, Cara J; Conn, Carole A.; Cohen, Deborah; Luo, Lei; Castillo, Joseph; Shah, Vallabh O.; Garver, William S.

doi:10.15436/2376-0494.15.024

Cited by 5 publications

(4 citation statements)

References 35 publications

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“…[18,20–22] Certain studies pointed out the fact that PNPLA3 gene increases hepatic steatosis by hindering TG decrease. [23] The variant allele of PNPLA3 rs738409 gene polymorphisms might contribute to the increase of AST and ALT, being correlated with age, gender, BMI and type 2 DM [57,58] in GG homozygotes of this SNP. Moreover, the same gene polymorphism seems to be involved in the development of non-alcoholic steatohepatitis (NASH) or type 1 DM.…”

Section: Discussionmentioning

confidence: 99%

“…[18,20–22] Garner underlined that homozygotes of the ancestral (C) allele of PNPLA3 rs738409 leads to a decrease of triglycerides (TG) in the liver, it's variant polymorphism increasing hepatic steatosis through the prevention of TG decrease. [23] Moreover, it seems that PNPLA3 rs738409 gene polymorphism is related to obesity and elevated levels of transaminases in teenagers suggesting that the early detection of its variant allele might be useful in the prevention of these disorders through a healthy and rigorous lifestyle. [24]…”

Section: Introductionmentioning

confidence: 99%

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The relationship among GNB3 rs5443, PNPLA3 rs738409, GCKR rs780094 gene polymorphisms, type of maternal gestational weight gain and neonatal outcomes (STROBE-compliant article)

Mărginean¹,

Bănescu

Meliţ

et al. 2019

Medicine

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The gestational weight gain is determined by food habits, environmental and genetic factors. The aims of this paper were to establish relationships between maternal gene polymorphisms (patatin-like phospholipase domain-containing protein 3 rs738409 [ PNPLA3 rs738409], glucokinase regulatory protein rs780094 [ GCKR rs780094], and guanine nucleotide-binding protein rs5443 [ GNB3 rs5443]) and mothers’ gestational weight gain, but also neonatal outcomes (birth weight, length, and ponderal index [PI]). We performed a cross-sectional study in a sample of 158 mothers and their product of conception’ in an Obstetrics-Gynecology Clinic from Romania. We divided the pregnant women according to the Institute of Medicine recommendations into 3 subgroups: (1) insufficient gestational weight gain; (2) normal gestational weight gain; and (3) excessive gestational weight gain. The gestational weight gain among pregnant women included in this study was classified as insufficient (10.1%), normal (31%), and excessive (58.9%). We found a tendency towards statistical significance for mothers that were overweight or obese before pregnancy to present an excessive gestational weight gain as compared to the normal weight ones. Similarly, we identified a tendency for statistical significance regarding the association between the variant genotype of GNB3 rs5443 and excessive gestational weight gain. We noticed differences that tended to be statistical significant concerning aspartate aminotransferase values between the 3 subgroups, mothers with excessive gestational weight gain having higher values than mothers with normal gestational weight gain (median, IQR: 22.89[17.53; 31.59] for mothers with excessive gestational weight gain versus 22.71[18.58; 27.37] for mothers with normal gestational weight gain). In mothers with excessive gestational weight gain, we found a significant association between the variant genotype of PNPLA3 rs738409 polymorphism and neonatal PI noticing a decrease of this index in case of newborns from mothers carrying the variant genotype. Excessive gestational weight gain was noticed in pregnant women that were obese and overweight before pregnancy. We found a positive association between the variant genotype of GNB3 rs5443 polymorphism and excessive gestational weight gain. Similarly, the presence of variant genotype of PNPLA3 rs738409 in mothers was associated with a lower PI in their newborns. Our study pointed out the most important factors that influence gestational weight gain and related birth outcomes.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The relationship among GNB3 rs5443, PNPLA3 rs738409, GCKR rs780094 gene polymorphisms, type of maternal gestational weight gain and neonatal outcomes (STROBE-compliant article)

Mărginean¹,

Bănescu

Meliţ

et al. 2019

Medicine

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“…The PEMT pathway, as represented within our studies, is necessary when cells lack an external supply to choline for the Kennedy pathway, which is the main source for PE and PC biosynthesis in mammals (Vance 2014). PEMT is low in most tissues with the exception of the liver and it has been reported that diabetic patients have significantly increased PEMT levels (Garner 2015).…”

Section: Characterizing the Role Of Agpat1/slc1 Lipotoxicity Suppress...mentioning

confidence: 54%

“…Metabolic diseases have been linked to genetic risk factors, with many genome-wide association (GWAS) studies providing single-nucleotide-polymorphism (SNP) associations with metabolic disease causing loci (Garner 2015). But the significant down-side to GWAS studies is the inability to determine if the mapped SNPs are associated with the underlying causal gene (Woo et al 2018), and many diseases are polygenic so single gene association studies become insufficient.…”

Section: Genetic Interaction Network (Gin) Analysismentioning

confidence: 99%

Identification and characterisation of the eukaryotic lipotoxicity interaction network (LIN) and modifiers of diacylglycerol-acyltransferase (DGAT)-mediated diseases

Joblin-Mills¹

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There is an ongoing need to understand the molecular mechanisms responsible for generating protective immunity to aid rational vaccine design. Various vaccine administration sites contain unique distributions of resident immune populations and other influencing factors in the microenvironment that may alter adaptive immune response generation. Typically, vaccination is administered intramuscularly or subcutaneously, however, many infectious diseases invade their hosts through the mucosal membranes, including the respiratory tract. Thereby, administering vaccines through the mucosa may represent a more natural infection route and establish specialised immune responses.To date, the importance of vaccine administration site remains unclear and thus should be investigated to understand whether specific local vaccination sites are of relevance in achieving desired immune responses. The main goal of vaccination is to activate antigen-presenting cells (APCs), such as dendritic cells (DCs), to then prime the adaptive immune response. DCs lie at the interface between innate and adaptive immunity, thus, to take up antigen they patrol body sites commonly invaded by pathogens, such as the skin and lung. Upon antigen uptake, DCs migrate to the draining lymph node to interact with T cells, resulting in CD4+ T cell activation and differentiation into distinct T helper subsets. Due to their remarkable ability to sense their environment and interact with pathogens, the context of DC activation instructs the adaptive immune response to react in the manner most suitable to eliminate the particular pathogen. Therefore, DCs are central to gaining a better understanding of the events involved in initiating an immune response. The aim of this investigation was to compare the immune cell composition and response in the skin and lung microenvironments. To address this, I used the novel vaccine adjuvant, αGalCer, which specifically activates innate-like natural killer T (NKT) cells and DCs, leading to peptide-specific T cell responses. APC activation and adaptive immune response generation were assessed in the skin and lung. I discovered that there was a greater proportion of T cells specialised to help B cells in the skin, compared to an enriched effector T cell phenotype in the lung. Additionally, the lung immune response was found to depend specifically on DC1 subset activation and the cytokine IFN-γ, likely produced by NKT cells upon activation, thus providing a mechanism for differential immune response generation in the skin and lung. These findings indicated that the tissue microenvironment could influence the adaptive immune response generated by vaccination, which is of great importance in the context of vaccine design.

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One-Carbon Metabolism and Nonalcoholic Fatty Liver Disease: The Crosstalk between Nutrients, Microbiota, and Genetics

et al. 2019

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The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide. Its etiology includes nutritional, genetic, and lifestyle factors. Several mechanisms may link one-carbon metabolism – the associated metabolic pathways of folate, methionine, and choline – to the onset of NAFLD. In this review, we attempted to assess how choline, folate, methionine, and betaine affect NAFLD development, mainly through their role in the secretion of very low-density lipoproteins (VLDL) from the liver. We also reviewed recent articles that have described the relation between microbiota metabolism and NAFLD progression. Moreover, we describe the effect of single-nucleotide polymorphisms (SNP) in genes related to one-carbon metabolism and disease prevalence. We additionally seek SNP identified by genome-wide associations that may increase the risk of this disease. Even though the evidence available is not entirely consistent, it seems that the concentrations of choline, methionine, folate, and betaine may affect the progression of NAFLD. Since there is no effective therapy for NAFLD, further investigations into the link between nutrition, gut microbiota, genetic factors, and NAFLD are still necessary, with a particular emphasis on methyl donors.

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NAFLD Susceptibility Genes and Their Association with Type 2 Diabetes and Obesity in a New Mexico Population

Cited by 5 publications

References 35 publications

The relationship among GNB3 rs5443, PNPLA3 rs738409, GCKR rs780094 gene polymorphisms, type of maternal gestational weight gain and neonatal outcomes (STROBE-compliant article)

The relationship among GNB3 rs5443, PNPLA3 rs738409, GCKR rs780094 gene polymorphisms, type of maternal gestational weight gain and neonatal outcomes (STROBE-compliant article)

Identification and characterisation of the eukaryotic lipotoxicity interaction network (LIN) and modifiers of diacylglycerol-acyltransferase (DGAT)-mediated diseases

One-Carbon Metabolism and Nonalcoholic Fatty Liver Disease: The Crosstalk between Nutrients, Microbiota, and Genetics

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