In the hepatocarcinogenesis of NAFLD&NASH in Figure 2, we also identified eight genes with differences in expression between NAFLD&NASH and HCC, i.e., HIST2H2BE (p value [less than or equal to] 1.00 x [10.sup.-3]), RFC5 (p value < 1.00 x [10.sup.-3]), HSPB1 (p value [less than or equal to] 1.00 x [10.sup.-3]), ZNF480 (p value [less than or equal to] 1.00 x [10.sup.-3]), TUBA1C (p value [less than or equal to] 1.00 x [10.sup.-3]), RPL30 (p value [less than or equal to] 1.00 x [10.sup.-3]), FRAT2 (p value [less than or equal to] 1.00 x [10.sup.-3]), and ALDOB (p value [less than or equal to] 1.5 x [10.sup.-2]).
In addition, the dysregulation of TUBA1C caused by abnormal miR-122 silencing and the dysregulation of ALDOB caused by both hypermethylation and abnormal miR-21 silencing might facilitate tumor metastasis.
In addition, we also found nine genes that play a central role in the upper progression path of Figure 1(a), i.e., two DNA repair-related genes (histone cluster 2 (H2be; HIST2H2BE) and replication factor C5 (RFC5)), four apoptosis-related genes (heat shock 27-kDa protein 1 (HSPB1), zinc finger protein 480 (ZNF480), tubulin alpha 1c (TUBA1C), and ribosomal protein L30 (RPL30)), and three metabolism-related genes (aldolase B (ALDOB), frequently rearranged in advanced T-cell lymphomas 2 (FRAT2), and tRNA methyltransferase 1 (TRMT1)).
In the analysis of the GSE12817 dataset, important genes such as Adm, Aldob, Pkm2, Crem, and nod3l were identified.
Aldob, Txnip, Crem, Adm, and Fos were found among the 16 most upregulated genes known to be strongly induced by high glucose.
These changes--often indicative of fructose intolerance--were correlated to a damaging mutation in ALDOB
(aldolase, fructose-bisphosphate B), which encodes the fructose-bisphosphate aldolase in the sorbitol degradation pathway.
Sheep gene mapping: Assignment of ALDOB
, CYP19, WT and SOX2 by somatic cell hybrid analysis.
Molecular Biology schemes: Factor V-Leiden, prothrombin, MTHFR, PAII (SERPINE1), factor XIII (F13A1), GPIIIa (1TGB3), [3Fib (FGB), VKORC1, Factor XII (F12), a1 PI, APOE, APOB, ACE, CETP, TPMT, CYP2C19, CYP2D6, CYP2C8, CYP2C9, UGT1A1 , DPD (DPYD), BCHE, ALDOB
, HFE, LCT, NOD2, ATP7B, FSAP (HABP2), ITGA2, KRAS.
Direct sequencing of exons 5 and 9 of the ALDOB gene (aldolase B, fructose-bisphosphate) (2) confirmed HFI due to a homozygous G>C transition in exon 5.
Mutations in the ALDOB gene on chromosome 9822.3 have been identified as the genetic cause of the disease.
We recommend that the laboratory instead perform genetic testing for HFI, which leads to a definitive diagnosis in most cases, because only 3 missense mutations in the ALDOB gene account for 85%-95% of the HFI alleles in different Caucasian populations (A149P, A174D, and N334K) (9, 10).
 Human genes: GALNT3, UDP-N-acetyl-[alpha]-D-galactosamine: polypeptide-N-acetylgalactosaminyltransferase 3; COG7, component of oligomeric golgi complex 7; LMNA, lamin A/C (previous symbols: LMN1, CMD1A); MGAT2, mannosyl (alpha-1,6-)-glycoprotein beta-1,2-N-acetylglucosaminyltransferase; GCS1, glucosidase; SLC35C1, solute carrier family 35, member C1; B4GALT1, UDP-Gal:betaGlcNAc beta 1,4-galactosyltransferase, polypepfide 1; SLC35A1, solute carrier family 35 (CMP-sialic acid transporter), member A1; POMGNTI, protein O-linked mannose beta 1,2-N-acetylglucosaminyltransferase; GNE, glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase; GALT, galactose-1-phosphate uridylyltransferase; ALDOB
, aldolase B, fructose-bisphosphate.