Whole-Exome Sequencing Identifies a Variant in Phosphatidylethanolamine N-Methyltransferase Gene to be Associated With Lean-Nonalcoholic Fatty Liver Disease

Bale, Gemma; Vishnubhotla, Ravikanth; Sasikala, Mitnala; Sharma, Mithun; Padaki, Rao N.; Pawar, Sunil; Duvvur, Reddy N.

doi:10.1016/j.jceh.2019.02.001

Cited by 35 publications

(30 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When most of the parameters are not significantly abnormal, the contribution of genes in the development of NAFLD should not be overlooked . A non-synonymous sequence variation (rs738409) in PNPLA3 that substitutes methionine for isoleucine at residue 148(I148M) was first reported to be associated with increased hepatic triglyceride content in a genome wide screen 34 . Single nucleotide polymorphism in the PNPLA3 gene has been associated with steatosis, fibrosis and elevated transaminases in individuals with NAFLD, with variations within different regions of India.…”

Section: Discussionmentioning

confidence: 99%

Difference in lifestyle and metabolic profile of non-alcoholic fatty liver disease with raised alanine amino-transferases between obese and non-overweight subjects

Sharma

Kulkarni

Kumar

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

A significant proportion of patients with non-alcoholic fatty liver disease (NAFLD) in Asian sub-continent are non-overweight and may have different underlying risk factors, lifestyles and metabolic profiles. Seven hundred fifty patients of NAFLD with raised alanine-amino-transferase (ALT) were divided into non-overweight and obese group based on their body mass index (BMI). Detailed dietary and lifestyle history were obtained through questionnaires and a detailed assessment of metabolic profile and liver stiffness was done. Normal BMI (< 23 kg/m2) was found in 6.6% patients, of which 69.5% had raised ALT. Though the intake of dietary fat and exercise pattern were not different amongst these groups, yet the amount of aerated drinks was higher in obese subjects (12 ± 17 vs. 7 ± 7.5 p = 0.005). Serum low-density lipoprotein (111 ± 25.6 vs. 127.7 ± 32.7 p = 0.04) and insulin resistance based on HOMA-IR > 2 were significantly higher in obese group (4.1 ± 0.36 vs. 2.0 ± 0.15 p = 0.001). Insulin resistance and dyslipidemia were prevalent in 12% and 25% non-overweight patients respectively. Metabolic syndrome was more common in obese subjects. In addition, magnetic resonance elastography showed higher mean liver fat in the obese group with similar hepatic fibrosis. Non-overweight patients with NAFLD had lower insulin resistance and prevalence of dyslipidaemia at similar dietary and exercise pattern.

show abstract

Section: Discussionmentioning

confidence: 99%

Difference in lifestyle and metabolic profile of non-alcoholic fatty liver disease with raised alanine amino-transferases between obese and non-overweight subjects

Sharma

Kulkarni

Kumar

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…Together with increased hepatic triglycerides, hepatic steatosis is associated with the depletion of liver phospholipids including PC and PE in morbidly obese mice [ 43 ] and NAFLD patients [ 44 ]. Studies in PEMT -deficient mice have indicated that a decrease in hepatic PC/PE ratio is linked to NAFLD [ 45 ], and variants of PEMT gene is associated with non-obese NAFLD [ 46 ]. HH subjects in our study had significantly higher serum PUFA-containing and total PE species and lower saturated-containing PC resulting in a decrease of PC/PE ratio.…”

Section: Discussionmentioning

confidence: 99%

“…HH subjects in our study had significantly higher serum PUFA-containing and total PE species and lower saturated-containing PC resulting in a decrease of PC/PE ratio. Thus, hepatic metabolism in steatotic HH may be dominated by a shift of metabolism towards PE as seen in PEMT -deficient mice [ 45 ] and non-obese NAFLD [ 46 ]. In support of our results, patients with NAFLD and NASH show higher hepatic PE and lower erythrocyte PC [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Plasma Lipidome, PNPLA3 polymorphism and hepatic steatosis in hereditary hemochromatosis

et al. 2020

View full text Add to dashboard Cite

Background Hereditary hemochromatosis (HH) is an autosomal recessive genetic disorder with increased intestinal iron absorption and therefore iron Overloa d. iron overload leads to increased levels of toxic non-transferrin bound iron which results in oxidative stress and lipid peroxidation. The impact of iron on lipid metabolism is so far not fully understood. The aim of this study was to investigate lipid metabolism including lipoproteins (HDL, LDL), neutral (triglycerides, cholesterol) and polar lipids (sphingo- and phospholipids), and PNPLA3 polymorphism (rs738409/I148M) in HH. Methods We conducted a cohort study of 54 subjects with HH and 20 healthy subjects. Patients were analyzed for their iron status including iron, ferritin, transferrin and transferrin saturation and serum lipid profile on a routine follow-up examination. Results HH group showed significantly lower serum phosphatidylcholine (PC) and significantly higher phosphatidylethanolamine (PE) compared to healthy control group. The ratio of PC/PE was clearly lower in HH group indicating a shift from PC to PE. Triglycerides were significantly higher in HH group. No differences were seen for HDL, LDL and cholesterol. Hepatic steatosis was significantly more frequent in HH. PNPLA3 polymorphism (CC vs. CG/GG) did not reveal any significant correlation with iron and lipid parameters including neutral and polar lipids, grade of steatosis and fibrosis. Conclusion Our study strengthens the hypothesis of altered lipid metabolism in HH and susceptibility to nonalcoholic fatty liver disease. Disturbed phospholipid metabolism may represent an important factor in pathogenesis of hepatic steatosis in HH.

show abstract

“…A recent exome‐wide association study showed a novel association of nuclear polymorphism rs4788084 with hepatic fat content, which regulates the expression of IL‐27, an immune‐regulatory gene 12 . A novel variant of phosphatidylethanolamine N ‐methyltransferase (involved in fatty acid metabolism), identified using whole‐exome sequencing, was shown to confer a three times greater risk for NAFLD in lean individuals 13 . There are some data that suggest that the genetic predisposition to NAFLD may vary according to ancestral ethnicity.…”

Section: Pathogenesis and Risk Factorsmentioning

confidence: 99%

Nonalcoholic Fatty Liver Disease: Indian Perspective

Duseja

2021

Clinical Liver Disease

View full text Add to dashboard Cite

show abstract

Whole-Exome Sequencing Identifies a Variant in Phosphatidylethanolamine N-Methyltransferase Gene to be Associated With Lean-Nonalcoholic Fatty Liver Disease

Cited by 35 publications

References 42 publications

Difference in lifestyle and metabolic profile of non-alcoholic fatty liver disease with raised alanine amino-transferases between obese and non-overweight subjects

Difference in lifestyle and metabolic profile of non-alcoholic fatty liver disease with raised alanine amino-transferases between obese and non-overweight subjects

Plasma Lipidome, PNPLA3 polymorphism and hepatic steatosis in hereditary hemochromatosis

Nonalcoholic Fatty Liver Disease: Indian Perspective

Contact Info

Product

Resources

About