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EBCR - Cut Neubi Getha
EBCR - Cut Neubi Getha
• The overall prevalence of NAFLD among patients with type 2 diabetes mellitus is 55.5%.
• The global prevalence of non-alcoholic steatohepatitis among patients with type 2 diabetes is 37.3%.
Younossi SM, et.al. The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: A systematic review and meta-analysis. J. Hepatol. 2019, 71, 793–801
INTRODUCTION
Kosmalski M. Non-Alcoholic Fatty Liver Disease or Type 2 Diabetes Mellitus—The Chicken or the Egg Dilemma. Biomedicines 2023, 11, 1097.
Genetic variants related to NAFLD T2D and glycemic trait associated variants
Sakurai Y, et.al. Role of Insulin Resistance in MAFLD. Int. J. Mol. Sci. 2021, 22(8), 4156
Prasad RB and Groop L. Genetics of Type 2 Diabetes—Pitfalls and Possibilities. Genes 2015, 6(1), 87-123
CASE ILUSTRATION
In the adult population with type 2 diabetes mellitus, is there a genetic relationship between type 2
diabetes and NAFLD?
Identification
Inclusion criteria :
1. Study designs are original articles of case control, cross-sectional, and systematic
review/meta-analysis (SR/MA) of case control
2. Full text published on English
3. Publication dates : 5 years
Exclusion criteria :
1. Eligibility based on PICO
2. Unpublished full text, books, literature reviews, case report, protocols
(N = 0 ) (N = 2) (N =3) (N = 1)
Critical Appraisal
Selected studies = 1
Tan, Y. et.al. Identification of shared genetic architecture between nonalcoholic fatty liver disease and type 2 diabetes: A genome-wide analysis. Front. Endocrinol. 14:1050049.
SUMMARY OF THE STUDY
Database Keywords
Tan, Y. et.al. Identification of shared genetic architecture between nonalcoholic fatty liver disease and type 2 diabetes: A genome-wide analysis. Front. Endocrinol. 14:1050049.
Tan, Y. et.al. Identification of shared genetic architecture between nonalcoholic fatty liver disease and type 2 diabetes: A genome-wide analysis. Front. Endocrinol. 14:1050049.
DISCUSSION
VPS53 → tumor Involved in endocytic recycling and retrograde transport, endosome to Golgi. Acts upstream of or within lysosomal transport
suppressor gene → Act as anti-tumor effect on liver cancer cells
SCGN SCGN-insulin interaction can stabilize insulin, enhance the hypoglycemic activity of insulin in vivo, and reduce hepatic steatosis and cholesterol
metabolism disorders
RGS6 → tumor • forms a complex with ATM in the liver, promotes ATM phosphorylation, and drives hepatic steatosis
suppressor gene • hepatic RGS6 increases oxidative stress and inflammation, which drive lipid deposition, fibrosis, and nonalcoholic fatty liver disease
SGCG effects on glucose homeostasis, and elevated levels in diabetic patients may be compensatory for IR
FOXN3 → tumor • associated with fasting blood glucose levels → hepatic FOXN3 increases fasting blood glucose by inhibiting hepatic glucose utilization while also
suppressor gene regulating the expression of amino acid transporters and catabolic enzymes
• FOXN3 suppresses the mRNA and protein expression of E2F5 by inhibiting the promoter activity of potential oncogene E2F5, thereby inhibiting
the proliferation of HCC cells in vitro and in vivo
DNAJB9 In ER lumen : promotes the degradation of the lipogenic transcription factor SREBP1c through ERAD
In ER membrane : promotes the assembly of mTORC2 in the cytosol and stimulates the synthesis of proteins and ATP
→ improves insulin sensitivity, restores protein synthesis, and suppresses food intake, accompanied by reduced hepatic steatosis and adiposity
CMAS encodes an enzyme that converts N-acetylneuraminic acid (NeuNAc) to cytidine 5'-monophosphate N-acetylneuraminic acid (CMP-NeuNAc). This
process is important in the formation of sialylated glycoprotein and glycolipids
Gene Role in NAFLD and Type 2 Diabetes
FASLG → tumor necrosis Induction of apoptosis triggered by binding to FAS. The FAS/FASLG signaling pathway is essential for immune system regulation, including
factor superfamily activation-induced cell death (AICD) of T cells and cytotoxic T lymphocyte induced cell death.
ABHD10 Encodes a mitochondrially-localized enzyme that acts in liver cells as a hydrolase. The encoded protein removes glucuronide from mycophenolic acid
acyl-glucuronide.
ATRN Encodes both membrane-bound and secreted protein isoforms.
• A membrane-bound isoform exhibits sequence similarity with the mouse mahogany protein, a receptor involved in controlling obesity.
• A secreted isoform is involved in the initial immune cell clustering during inflammatory responses that may regulate the chemotactic activity of
chemokines
PLA2G2F Enables calcium-dependent phospholipase A2 activity. Involved in glycerophospholipid metabolic process. Predicted to be located in cytosol and
extracellular region
ITIH2 encodes a preproprotein that is proteolytically processed to generate the heavy chain of the inter-alpha-trypsin inhibitor complex, which is secreted
by hepatocytes into the blood.
Strength Limitation
The first study combined Study only included GWAS
GWAS and DEG analysis to from European population
identify shared genes for
Study only focused on the loci
STRENGTH NAFLD and T2D. that achieve the significance
threshold for genome-wide
and association
LIMITATION
CONCLUSION
There is causal relationship between NAFLD and T2D. Fifteen core genes (DNAJB9, VPS53, SCGN, CMAS, RGS6,
FASLG, ABHD10, ATRN, PLA2G2F, ITIH2, ROBO1, SGCG, SH3GL2, CNR1, and FOXN3) are known to be shared
between NAFLD and T2D
Thank You