PNPLA3 I148M Polymorphism in Patients with Nonalcoholic Fatty Liver Disease, Obesity and Prediabetes

Karamfilova, Vera; Gateva, Antoaneta; Assyov, Yavor; Alexiev, A.; Savov, Alexey; Yaneva, N.; Ivanova, Irena; Ivanova-Boyanova, Radina; Ivanova, Raya; Vlahova, Zlatina; Mateva, Л.; Kamenov, Zdravko

doi:10.15403/jgld-506

Cited by 15 publications

(13 citation statements)

References 34 publications

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“…In our study, The PNPLA3 rs738409 gene polymorphism frequency was highly significant in diabetic obese patients when compared to diabetic none obese group. This result goes with that of Karamfilova et al [45] who demonstrated a relationship between diabetes mellitus and the PNPLA3I148M allele. Significantly higher percentage of CG and GG genotype was found in patients with insulin resistance.…”

Section: Plos Onesupporting

confidence: 92%

Gene polymorphisms of Patatin-like phospholipase domain containing 3 (PNPLA3), adiponectin, leptin in diabetic obese patients

et al. 2020

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Obesity leads a crucial importance in metabolic disorders, as well as type 2 diabetes mellitus. Our present study was designed to assess the potential role of irisin, adiponectin, leptin and gene polymorphism of PNPLA3, leptin and adiponectin as predictive markers of diabetes associated with obesity. One hundred eighty subjects were distributed to three groups including; healthy non-diabetic non obese volunteers as a control group, diabetic non obese group, and diabetic obese group (n = 60 for each group). Fasting blood samples of all groups were collected to determine fasting blood glucose, insulin levels, insulin resistance, total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triacylglycerol, irisin, adiponectin, leptin; as well as, polymorphism of PNPLA3, adiponectin and leptin. The results showed that glucose, insulin resistance, total cholesterol, irisin, leptin, LDL-C, triacylglycerol concentrations were significantly increased, however, insulin, HDL-C, adiponectin were significantly decreased in diabetic obese patients in relation to diabetic non-obese patients as well as in healthy volunteers. The polymorphism of PNPLA3 rs738409 was linearly related to irisin and leptin but was not related with circulating concentrations of adiponectin. We concluded that increased irisin and leptin levels can predict the insulin resistance in obese patients. Moreover, patients who have mutant genotype of PNPLA3 I148 gene (rs738409) C>G, ADIPOQ gene (rs266729) G>C and LEP gene (rs2167270) G>A showed a significant higher susceptibility rate for DM in obese people than those with wild type. This could be considered as an adjustable retort to counter the impact of obesity on glucose homeostasis.

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Section: Plos Onesupporting

confidence: 92%

Gene polymorphisms of Patatin-like phospholipase domain containing 3 (PNPLA3), adiponectin, leptin in diabetic obese patients

et al. 2020

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“…By 2030, the number of NAFLD cases is expected to reach 100.9 million [26]. Overnutrition and sedentary lifestyle have been considered as the main causes of NAFLD [27] and genetic variants, including PNPLA3 rs738409, TM6SF2 rs58542926 and HSD17B13 rs72613567, in patients may accelerate or decelerate the progression of NAFLD [28–30]. The present study focused on another candidate gene, SAMM50 , aiming to investigate its association with NAFLD in a Chinese cohort (Table S4).…”

Section: Discussionmentioning

confidence: 99%

The role of SAMM50 in non‐alcoholic fatty liver disease: from genetics to mechanisms

Shen

et al. 2021

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Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic lipid accumulation. SAMM50 encodes Sam50, a mitochondrial outer membrane protein involved in the removal of reactive oxygen species, mitochondrial morphology, and regulation of mitophagy. Certain single nucleotide polymorphisms (SNPs) of SAMM50 have been reported to be correlated with NAFLD. However, the contribution of SAMM50 polymorphisms to the occurrence and severity of fatty liver in the Chinese Han cohort has rarely been reported. Here, we investigated the association between SAMM50 polymorphisms (rs738491 and rs2073082) and NAFLD in a Chinese Han cohort, as well as the mechanistic basis of this association. Clinical information and blood samples were collected from 380 NAFLD cases and 380 normal subjects for the detection of genotypes and biochemical parameters. Carriers of the rs738491 T-allele or rs2073082 G-allele of SAMM50 exhibit increased susceptibility to NAFLD (OR=1.39; 95% CI=1.14-1.71, P=0.001; OR=1.31; 95% CI=1.05-1.62, P=0.016, respectively) and are correlated with elevated serum TG, ALT, and AST levels. The presence of the T allele (TT+CT) of rs738491 (P<0.01) or G allele (AG+GG) of rs2073082 (P=0.03) is correlated with the severity of fatty liver in the NAFLD cohort. In vitro studies indicated that SAMM50 gene polymorphisms decrease its expression and SAMM50 deficiency results in increased lipid

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“… 16 , 25 The PNPLA3 I148M polymorphism also reportedly increased the risk of insulin resistance, obesity, and systemic inflammation. 26 - 28 Indeed, previous studies demonstrated that accelerated lung function decline is attributed to insulin resistance. 19 The associations among lung function, BMI, and systemic inflammation have been well studied.…”

Section: Discussionmentioning

confidence: 99%

Impact of Evolutionary Changes in Nonalcoholic Fatty Liver Disease on Lung Function Decline

et al. 2022

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Background/Aims A relationship between fatty liver and lung function impairment has been identified, and both are independently associated with metabolic dysfunction. However, the temporal relationship between changes in fatty liver status and lung function and their genome-wide association remain unclear. Methods This longitudinal cohort consisted of subjects who received serial health check-ups, including liver ultrasonography and spirometry, for ≥3 years between 2003 and 2015. Lung function decline rates were classified as “slow” and “accelerated” and compared among four different sonographic changes in steatosis status “normal,” “improved,” “worsened,” and “persistent.” A genome-wide association study was conducted between the two groups normal/improved steatosis with a slow decline in lung function versus worsened/persistent steatosis with an accelerated decline in lung function. Results Among 6,149 individuals, the annual rates of decline in forced vital capacity (FVC) and forced expiratory volume measured in the first second of exhalation (FEV 1 ) were higher in the worsened/persistent steatosis group than in the normal/improved steatosis group. In multivariable analysis, persistent or worsened status of fatty liver was significantly associated with accelerated declines in FVC (persistent status, odds ratio [OR]=1.22, 95% confidence interval [CI]=1.04–1.44; worsened status, OR=1.30, 95% CI=1.12–1.50), while improved status of fatty liver was significantly associated with slow declines in FEV 1 (OR=0.77, 95% CI=0.64–0.92). The PNPLA3 risk gene was most strongly associated with steatosis status change and accelerated declines in FVC (rs12483959, p=2.61×10 -7 ) and FEV 1 (rs2294433, p=3.69×10 -8 ). Conclusions Regression of fatty liver is related to lung function decline. Continuing efforts to improve fatty liver may preserve lung function, especially for subjects with a high genetic risk.

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PNPLA3 I148M Polymorphism in Patients with Nonalcoholic Fatty Liver Disease, Obesity and Prediabetes

Cited by 15 publications

References 34 publications

Gene polymorphisms of Patatin-like phospholipase domain containing 3 (PNPLA3), adiponectin, leptin in diabetic obese patients

Gene polymorphisms of Patatin-like phospholipase domain containing 3 (PNPLA3), adiponectin, leptin in diabetic obese patients

The role of SAMM50 in non‐alcoholic fatty liver disease: from genetics to mechanisms

Impact of Evolutionary Changes in Nonalcoholic Fatty Liver Disease on Lung Function Decline

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