Genetic determinants of hepatic steatosis in man.
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ABSTRACT:
SUBMITTER: Hooper AJ
PROVIDER: S-EPMC3053205 | biostudies-literature | 2011 Apr
REPOSITORIES: biostudies-literature
Publications
Genetic determinants of hepatic steatosis in man.
Hooper Amanda J AJ Adams Leon A LA Burnett John R JR
Journal of lipid research 20110118 4
Hepatic steatosis is one of the most common liver disorders in the general population. The main cause of hepatic steatosis is nonalcoholic fatty liver disease (NAFLD), representing the hepatic component of the metabolic syndrome, which is characterized by type 2 diabetes, obesity, and dyslipidemia. Insulin resistance and excess adiposity are considered to play key roles in the pathogenesis of NAFLD. Although the risk factors for NAFLD are well established, the genetic basis of hepatic steatosis ...[more]
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Project description:Introduction and objectivesVarious studies have identified single-nucleotide polymorphisms (SNPs) associated with nonalcoholic fatty liver disease (NAFLD) and related traits, including ones located in or near the LYPLAL1, GCKR, PPP1R3B, TM6SF2, MBOAT7, and PNPLA3 genes. However, these SNPs were identified primarily in populations of European ancestry. This study examined the associations of these previously identified SNPs with hepatic steatosis in a sample of Mexican-origin adults living in Southern Arizona.Materials and methodsA total of 307 Mexican-origin adults between the ages of 18 and 64 with a body mass index (BMI) of 25 kg/m2 or higher were genotyped at the following SNPs: rs12137855 (LYPLAL1), rs1260326 (GCKR), rs4240624 (PPP1R3B), rs58542926 (TM6SF2), rs641738 (MBOAT7), and rs738409 (PNPLA3). Hepatic steatosis was assessed by transient elastography (FibroScan®) with controlled attenuation parameter. Regression models examined the association between each of the six SNPs and hepatic steatosis. BMI was examined as a potential modifier of the genetic associations.ResultsParticipants were, on average, 45 years old and mostly female (63%) with an overall mean hepatic steatosis of 288.1 dB/m. Models showed no associations between LYPLAL1, GCKR, PPP1R3B, TM6SF2, or MBOAT7 and hepatic steatosis. Only PNPLA3 was statistically significantly associated with hepatic steatosis in both unadjusted and adjusted models (p<0.01). There was no effect modification observed with BMI.ConclusionsSNPs associated with NAFLD in populations of European descent did not strongly contribute to hepatic steatosis in individuals of Mexican-origin, except for rs738409 (PNPLA3). Further efforts are necessary to explore additional SNPs that may be associated with NAFLD in this high-risk population.
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Project description:The etiology of nonalcoholic fatty liver disease is complex and influenced by factors such as obesity, insulin resistance, hyperlipidemia, and sex. We now report a study on sex difference in hepatic steatosis in the context of genetic variation using a population of inbred strains of mice. While male mice generally exhibited higher concentration of hepatic TG levels on a high-fat high-sucrose diet, sex differences showed extensive interaction with genetic variation. Differences in percentage body fat were the best predictor of hepatic steatosis among the strains and explained about 30% of the variation in both sexes. The difference in percent gonadal fat and HDL explained 9.6% and 6.7% of the difference in hepatic TGs between the sexes, respectively. Genome-wide association mapping of hepatic TG revealed some striking differences in genetic control of hepatic steatosis between females and males. Gonadectomy increased the hepatic TG to body fat percentage ratio among male, but not female, mice. Our data suggest that the difference between the sexes in hepatic TG can be partly explained by differences in body fat distribution, plasma HDL, and genetic regulation. Future studies are required to understand the molecular interactions between sex, genetics, and the environment.
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Project description:Hepatic steatosis is a common finding in liver biopsy and may co-exist with chronic hepatitis B (CHB) infection. The aims of this study were to determine the prevalence of steatosis in CHB patients among Filipinos; determine the factors related to the presence of steatosis among individuals with and without CHB infection; and to investigate the possible association between steatosis and polymorphism in interleukin 28B (IL28B) gene. The presence of steatosis was correlated with clinical, biochemical and histological parameters. Peripheral blood samples of CHB patients with steatosis, CHB patients without steatosis and normal controls were genotyped for IL28B rs8099917 T>G using the TaqMan assay. Of the 46 CHB patients, 41% (19/46) had steatosis. Body mass index (BMI), fasting blood sugar (FBS), lipid profile and alanine transaminase levels were observed to be significantly different between CHB patients with steatosis and normal controls. The serum FBS of CHB patients with steatosis was significantly higher than patients without steatosis. High density lipoprotein cholesterol of patients without steatosis was significantly higher than patients with steatosis. Although not statistically significant, BMI, triglycerides, low density lipoprotein cholesterol and histology activity index in CHB patients with steatosis were found to be higher than those without steatosis. There was no significant association between the stage of fibrosis and severity of steatosis. In conclusion, the prevalence of hepatic steatosis among Filipino patients with CHB is 41%. Steatosis in CHB patients was associated with metabolic factors such as diabetes and dyslipidemia. IL28B rs8099917 T>G polymorphism is not associated with steatosis.
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Project description:CPEB4 prevents hepatic steatosis
| PRJNA322835 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2017-01-16 | GSE81877 | GEO
Project description:Nonalcoholic steatosis (fatty liver) is a major cause of liver dysfunction that is associated with insulin resistance and metabolic syndrome. The cJun NH(2)-terminal kinase 1 (JNK1) signaling pathway is implicated in the pathogenesis of hepatic steatosis and drugs that target JNK1 may be useful for treatment of this disease. Indeed, mice with defects in JNK1 expression in adipose tissue are protected against hepatic steatosis. Here we report that mice with specific ablation of Jnk1 in hepatocytes exhibit glucose intolerance, insulin resistance, and hepatic steatosis. JNK1 therefore serves opposing actions in liver and adipose tissue to both promote and prevent hepatic steatosis. This finding has potential implications for the design of JNK1-selective drugs for the treatment of metabolic syndrome.
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Project description:Objective:Comorbid NAFLD is increasingly being diagnosed in patients with diabetes and nondiabetic endocrinopathies. The aim of this study was to assess hepatic steatosis noninvasively by transient elastography in patients with acromegaly. Design:A cross-sectional study including 22 patients with acromegaly. Methods:Hepatic steatosis was quantified using controlled attenuation parameter (CAP) during elastography. Anthropometric measurements were obtained, serum liver function tests and lipid and hormone profiles were measured, and prosteatogenic gene variants were genotyped using standard assays. Results:In total, 41% of patients were women (mean age 60 ± 14.7 years, mean BMI 31.2 ± 4.6 kg/m2). Hepatic steatosis, as defined by CAP > 248 dB/m, was present in 66% of patients. Five (45%) of the patients with hepatic steatosis also had fibrosis, and one presented with cirrhosis. Nine patients were carriers of the PNPLA3 p.I148M prosteatogenic [M] risk allele, eight of whom were heterozygotes. CAP values were significantly (P = .045) higher in these patients and corresponded to advanced steatosis, as compared to patients with the wild-type genotype, who demonstrated CAP values consistent with mild steatosis (311 ± 33 dB/m. vs 254 ± 62 dB/m). CAP values did not differ significantly in carriers of distinct TM6SF2 and MBOAT7 genotypes; however, carriers of the risk alleles displayed higher CAP as compared to wild-type patients. Conclusions:This study shows that in patients with acromegaly, carriers of the PNPLA3 susceptibility allele are at risk of developing hepatic steatosis, as assessed by CAP. Comorbid NAFLD might compound prognosis in such patients; thus, further research into the pathomechanisms and treatment of NAFLD in acromegaly is warranted.
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