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

ABSTRACT: 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.

SUBMITTER: Aly O

PROVIDER: S-EPMC7297308 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Aly Omnia O Zaki Hanan Hassan HH Herzalla Mohamed R MR Fathy Ahmed A Raafat Nermin N Hafez Mohamed M MM

PloS one 20200616 6

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 e ...[more]

PMID: 32544194

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Project description:BackgroundTo investigate the correlation between rs738409 polymorphism of patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene (encoding I148m) and genetic susceptibility to nonalcoholic fatty liver disease (NAFLD).MethodsWeb of Science, Embase, PubMed, Cochrane Library, China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform databases were subjected to study retrieving, from the earliest records to November 2022. International databases were searched using the key words (PNPLA3 gene or PNPLA3 polymorphism or patatin-like phospholipase domain-containing pro-tein3) and (nonalcoholic fatty liver disease or NAFLD or nonalcoholic steatohepatitis) and their possible combination. There was no limitation to language. Ethnicity and country restrictions were not applied. Hardy-Weinberg equilibrium about the genotype frequencies of rs738,409 polymorphism in group of controls was assessed using a chi-square goodness-of-fit test (P > .05). A chi-square-based Q test was applied to assess heterogeneity among studies. The random-effect model (DerSimonian-Laird method) was used when a probability value of P < .10, I2 > 50%. If not, the fixed-effect model (Mantel-Haenszel method) was adopted. The current meta-analysis was done by using STATA 16.0.ResultsTwenty studies are selected for this meta-analysis, which includes totally 3240 patients in the treatment group and 5210 patients in the control group. These studies demonstrated a significant increased association between rs738,409 and NAFLD under 5 models: allelic contrast (odds ratio [OR] = 1.98, 95% confidence interval [CI] = 1.65-2.37, Pheterogeneity = 0.000, Z = 7.346, P = .000), homozygote comparison (OR = 3.59, 95% CI = 2.56-5.04, Pheterogeneity = 0.000, Z = 7.416, P = .000), heterozygote comparison (OR = 1.93, 95% CI = 1.63-2.30, Pheterogeneity = 0.002, Z = 7.507, P = .000), the dominant allele model (OR = 2.33, 95% CI = 1.89-2.88, Pheterogeneity = 0.000, Z = 7.856, P = .000), and the recessive allele model (OR = 2.56, 95% CI = 1.96-3.35, Pheterogeneity = 0.000, Z = 6.850, P = .000). Subgroup analysis shows that the rs738,409 polymorphism of PNPLA3 gene in Caucasians and those with a sample size of < 300 is significantly associated with the susceptibility to nonalcoholic fatty liver. Sensitivity analysis shows that the results of meta-analysis are stable.ConclusionPNPLA3 rs738,409 may play a significant role in increasing risk of NAFLD.

Project description:UnlabelledGenome-wide association studies identified single-nucleotide polymorphisms (SNPs) that are associated with increased hepatic fat or elevated liver enzymes, presumably reflecting nonalcoholic fatty liver disease (NAFLD). To investigate whether these SNPs are associated with histological severity of NAFLD, 1117 (894 adults/223 children) individuals enrolled in the Nonalcoholic Steatohepatitis (NASH) Clinical Research Network and National Institutes of Health Clinical Center studies with histologically confirmed NAFLD were genotyped for six SNPs that are associated with hepatic fat or liver enzymes in genome-wide association studies. In adults, three SNPs on chromosome 22 showed associations with histological parameters of NASH. After adjustment for age, sex, diabetes, and alcohol consumption, the minor allele of rs738409 C/G, a nonsynonymous coding SNP in the patatin-like phospholipase domain-containing protein 3 (PNPLA3) (adiponutrin) gene encoding an Ile148Met change, was associated with steatosis (P = 0.03), portal inflammation (P = 2.5 x 10(-4)), lobular inflammation (P = 0.005), Mallory-Denk bodies (P = 0.015), NAFLD activity score (NAS, P = 0.004), and fibrosis (P = 7.7 x 10(-6)). Two other SNPs in the same region demonstrated similar associations. Three SNPs on chromosome 10 near the CHUK (conserved helix-loop-helix ubiquitous kinase) gene were independently associated with fibrosis (P = 0.010). In children, no SNP was associated with histological severity. However, the rs738409 G allele was associated with younger age at the time of biopsy in multivariate analysis (P = 0.045).ConclusionIn this large cohort of histologically proven NAFLD, we confirm the association of the rs738409 G allele with steatosis and describe its association with histological severity. In pediatric patients, the high-risk rs738409 G allele is associated with an earlier presentation of disease. We also describe a hitherto unknown association between SNPs at a chromosome 10 locus and the severity of NASH fibrosis.

Project description:To investigate whether the patatin-like phospholipase domain containing-3 gene (PNPLA3) I148M polymorphism is associated with steatosis, fibrosis stage, and cirrhosis in hereditary hemochromatosis (HH).We studied 174 consecutive unrelated homozygous for the C282Y HFE mutation of HH (C282Y+/+ HH) patients from Northern Italy, for whom the presence of cirrhosis could be determined based on histological or clinical criteria, without excessive alcohol intake (< 30/20 g/d in males or females) or hepatitis B virus and hepatitis C virus viral hepatitis. Steatosis was evaluated in 123 patients by histology (n = 100) or ultrasound (n = 23). The PNPLA3 rs738409 single nucleotide polymorphism, encoding for the p.148M protein variant, was genotyped by a Taqman assay (assay on demand, Applied Biosystems). The association of the PNPLA3 I148M protein variant (p.I148M) with steatosis, fibrosis stage, and cirrhosis was evaluated by logistic regression analysis.PNPLA3 genotype was not associated with metabolic parameters, including body mass index (BMI), the presence of diabetes, and lipid levels, but the presence of the p.148M variant at risk was independently associated with steatosis [odds ratio (OR) 1.84 per p.148M allele, 95% confidence interval (CI): 1.05-3.31; P = 0.037], independently of BMI and alanine aminotransaminase (ALT) levels. The p.148M variant was also associated with higher aspartate aminotransferase (P = 0.0014) and ALT levels (P = 0.017) at diagnosis, independently of BMI and the severity of iron overload. In patients with liver biopsy, the 148M variant was independently associated with the severity (stage) of fibrosis (estimated coefficient 0.56 ± 0.27, P = 0.041). In the overall series of patients, the p.148M variant was associated with cirrhosis in lean (P = 0.049), but not in overweight patients (P = not significant). At logistic regression analysis, cirrhosis was associated with BMI ? 25 (OR 1.82, 95% CI: 1.02-3.55), ferritin > 1000 ng/mL at diagnosis (OR 19.3, 95% CI: 5.3-125), and with the G allele in patients with BMI < 25 (OR 3.26, 95% CI: 1.3-10.3).The PNPLA3 I148M polymorphism may represent a permissive factor for fibrosis progression in patients with C282Y+/+ HH.

Dataset Information

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

Publications

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

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