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Abstract Objective This study aims to explore ADH4 expression in hepatocellular carcinoma (HCC), its prognostic impact, and its immune correlation to provide novel insights into HCC prognostication and treatment. Methods HCC prognostic marker genes were rigorously selected using GEO database, Lasso regression, GEPIA, Kaplan-Meier and pROC analyses. The expression of interested markers (ADH4, DNASE1L3, RDH16, LCAT, HGFAC) in HCC and adjacent tissues was assessed by Immunohistochemistry (IHC). We observed that ADH4 exhibited low expression levels in liver cancer tissues and high expression levels in normal liver tissues. However, the remaining four genes did not manifest any statistically significant differences between hepatocellular carcinoma (HCC) tissue and adjacent non-cancerous tissue. Consequently, ADH4 became the primary focus of our research. ADH4 expression was validated by signed-rank tests and unpaired Wilcoxon rank sum tests across pan-cancer and HCC datasets. Clinical significance and associations with clinicopathological variables were determined using Kaplan-Meier, logistic regression and Cox analyses on TCGA data. The ADH4-related immune responses were explored by Spearman correlation analysis using TIMER2 data. CD68, CD4, and CD19 protein levels were confirmed by IHC in HCC and non-cancerous tissues. Results ADH4 showed significant downregulation in various cancers, particularly in HCC. Moreover, low ADH4 expression was associated with clinicopathological variables and served as an independent prognostic marker for HCC patients. Additionally, ADH4 affects a variety of biochemical functions and may influence cancer development, prognosis, and treatment by binding to immune cells. Furthermore, at the immune level, the low expression pattern of ADH4 is TME-specific, indicating that ADH4 has the potential to be used as a target for cancer immunotherapy. Conclusion This study highlights the diagnostic, prognostic and immunomodulatory roles of ADH4 in HCC. ADH4 could serve as a valuable biomarker for HCC diagnosis and prognosis, as well as a potential target for immunotherapeutic interventions.

Due to their high reactivity, volatile organic compounds (VOCs) can engage in physical and chemical reactions with particulate matter in the atmosphere, leading to air pollution. Extended exposure to VOCs may result in various health concerns, including respiratory system problems, neurological effects, skin and eye irritation, and an increased risk of certain cancers. Traditional benchtop mass spectrometers possess the advantages of high sensitivity and rapid analysis capabilities, but the large size typically confines their applications to professional laboratories. To overcome this limitation, portable mass spectrometers are emerging as a new tool for in-situ analysis. In this study, a portable mass spectrometer based on discontinuous atmosphere pressure interface was developed, which combined with a sub-vacuum plasma ionization source. Ion trap, known for its small size and adequate performance, was adopted in this miniaturized mass spectrometer. This portable mass spectrometer features a total weight of about 4.6 kg, with the dimensions of 217 mm×162 mm×106 mm, and operates with a power consumption under 150 W. On this design, a fully metallic solenoid valve was selected as the core component to limit atmospheric pressure, eliminating the need for the rubber tubing used in traditional pinch valves. Compared to traditional pinch valves, this solenoid valve ensures a more stable airflow during experiments. As a result, the repeatability and environmental adaptability of the portable mass spectrometer were improved. A certain delay marked as radio freqency (RF) delay was introduced between the injection and cooling periods, and the RF-delay time was optimized. Frequency scanning mode and amplitude scanning mode were tested in parallel. Despite of a trade-off in size, amplitude scanning offered improved resolution, enabling the differentiation of ions with close mass to charge ratios. After systematic optimization, satisfactory performances in mass resolution and sensitivity were achieved. The mass resolution of the mass spectrometer for dimethyl carbonate was improved to 0.2 u (FWHM), and a sensitivity of 60 μg/m3 for naphthalene was achieved. The capability of mixed VOCs was also validated using dimethyl carbonate and trimethyl phosphate. This mass spectrometer developed in this study, characterized by its high portability and satisfactory performance, is expected to hold great potential for applications in VOCs analysis.

The Xiaoqinling gold province, located in the southern margin of the North China Craton (NCC), is the second largest gold-enriched region in China. In this region, the Mesozoic Huashan (HS) and Wenyu (WY) plutons are the major magmatic intrusions coeval with gold mineralization, although they show contrasting characteristics in the distribution of gold. In this study, we use geochemical features of titanite determined by LA-ICP-MS and EPMA analyses and elemental mapping to decipher the mechanisms that led to the difference in gold enrichment related to the two plutons. Titanite from the Wenyu granitic pluton exhibits significantly higher (La/Sm)N, (La/Yb)N, ΣLREE/ΣHREE ratios, and ΣREE concentration and slightly higher (Gd/Yb)N values than those of the Huashan Pluton, suggesting that the Wenyu pluton might have experienced more complex magmatic evolution, widespread hydrothermal alteration, and higher silica activity in the melt than the Huashan pluton. The titanite grains from the Huashan pluton show higher (Nb/Ta)N and (Lu/Hf)N values and significantly lower Zr concentration than those of the Wenyu pluton. The titanite grains from the Wenyu pluton show higher vanadium and gallium concentrations and Fe/Al ratio than those of the Huashan pluton, indicating comparatively higher fo2. Furthermore, the titanite grains from Wenyu pluton indicate higher water content in the magma. In addition, magma mingling and magmatic hydrothermal fluids derived from the crust/mantle are critical sources for ore-forming materials. These results suggest that the Wenyu pluton is more conducive to gold migration and enrichment than the Huashan pluton.

Abstract Background Hypercholesterolemia and gut microbiota dysbiosis are associated with the risk of cardiovascular diseases. Hawthorn fruits has shown to be cardioprotective and hypocholesterolemic. However, no studies to date have studied the biological activity of hawthorn seed oil (HSO). The present study was to investigate if HSO could favourably reduce plasma cholesterol and modulate gut microbiota in hypercholesterolemia hamsters. Methods Golden Syrian hamsters (age, 8 weeks) were randomly divided into five groups (n = 8, each) and fed one of the following five diets, namely a non-cholesterol diet, a high cholesterol diet containing 0.15% cholesterol (HCD); a HCD diet with addition of 4.75% HSO (LHSO), a HCD diet with addition of 9.5% HSO (HHSO), a HCD diet with addition of 0.50% cholestyramine as positive control diet. After 6-week dietary intervention, plasma lipids, inflammatory markers, atherosclerosis plaque, hepatic and fecal lipids were quantified. Microbiota in fresh feces were analysed by sequencing 16S rRNA genes, while RT-PCR and Western blot analyses were employed to quantify the expression of genes involved in cholesterol homeostasis. Results HSO at a dose of 9.5% HSO could decrease plasma cholesterol and non-HDL-cholesterol by 15%. Additionally, both HSO experimental groups also suppressed mRNA of 3-Hydroxy-3-Methylglutaryl-CoA Reductase (HMG-CoA-R). Supplementation of HSO at 4.75% could significantly increase the excretion of fecal acidic sterols, accompanied by elevation of short-chain fatty acid levels in feces. The analyses of gut microbiome indicated that HSO supplementation could selectively alter the genera abundance of gut bacteria that were correlated with cholesterol metabolism including unclassified_f__Christensenellaceae, Ruminococcaceae_NK4A214_ group, norank_o_Gastranaerophilales, Faecalibaculum, Peptococcus, norank_f__Clostridiales_vadinBB60_group and Ruminococcus_2. Conclusions HSO supplementation was able to decrease plasma cholesterol by favourably modulating gut microbiota composition and gut-derived metabolites associated with cholesterol regulation. Graphical Abstract

Abstract We aimed to examine whether the efficacy of the risk of poor prognosis in patients with coronary artery disease is jointly affected by total cholesterol and baseline serum albumin in a secondary analysis of previous study. We analyzed the data of 204 patients from October 2014 to October 2017 for newly diagnosed stable CAD. The outcome was major adverse cardiac events (MACE; defined as all cause mortality, non fatal myocardial infarction, and non fatal stroke). The median duration of follow-up was 783 days. Multivariable COX model was performed to revalidate the relationship between the sALB and MACE and interaction tests were conducted to find the effects of total cholesterol on their association. A total of 28 MACE occurred among the 204 participants. The risk of MACE varied by baseline serum albumin and total cholesterol. Specifically, lower serum albumin indicated higher risk of MACE (HR 3.52, 95% CI 1.30–9.54), and a test for interaction between baseline serum albumin and total cholesterol on MACE was significant (P = 0.0005). We suggested that baseline serum albumin and total cholesterol could interactively affect the risk of poor prognosis of patients with coronary artery diseases. Our findings need to be confirmed by further randomized trials.

BackgroundCardiovascular diseases (CVDs) have been the major cause of mortality in type 2 diabetes. However, new approaches are still warranted since current diabetic medications, which focus mainly on glycemic control, do not effectively lower cardiovascular mortality rate in diabetic patients. Protocatechuic acid (PCA) is a phenolic acid widely distributed in garlic, onion, cauliflower and other plant-based foods. Given the anti-oxidative effects of PCA in vitro, we hypothesized that PCA would also have direct beneficial effects on endothelial function in addition to the systemic effects on vascular health demonstrated by previous studies.Methods and resultsSince IL-1β is the major pathological contributor to endothelial dysfunction in diabetes, the anti-inflammatory effects of PCA specific on endothelial cells were further verified by the use of IL-1β-induced inflammation model. Direct incubation of db/db mouse aortas with physiological concentration of PCA significantly ameliorated endothelium-dependent relaxation impairment, as well as reactive oxygen species overproduction mediated by diabetes. In addition to the well-studied anti-oxidative activity, PCA demonstrated strong anti-inflammatory effects by suppressing the pro-inflammatory cytokines MCP1, VCAM1 and ICAM1, as well as increasing the phosphorylation of eNOS and Akt in the inflammatory endothelial cell model induced by the key player in diabetic endothelial dysfunction IL-1β. Upon blocking of Akt phosphorylation, p-eNOS/eNOS remained low and the inhibition of pro-inflammatory cytokines by PCA ceased.ConclusionPCA exerts protection on vascular endothelial function against inflammation through Akt/eNOS pathway, suggesting daily acquisition of PCA may be encouraged for diabetic patients.

The gut microbiota serves as a pivotal mediator between diet and human health. Emerging evidence has shown that the gut microbiota may play an important role in cholesterol metabolism. In this review, we delve into five possible mechanisms by which the gut microbiota may influence cholesterol metabolism: (1) the gut microbiota changes the ratio of free bile acids to conjugated bile acids, with the former being eliminated into feces and the latter being reabsorbed back into the liver; (2) the gut microbiota can ferment dietary fiber to produce short-chain fatty acids (SCFAs) which are absorbed and reach the liver where SCFAs inhibit cholesterol synthesis; (3) the gut microbiota can regulate the expression of some genes related to cholesterol metabolism through their metabolites; (4) the gut microbiota can convert cholesterol to coprostanol, with the latter having a very low absorption rate; and (5) the gut microbiota could reduce blood cholesterol by inhibiting the production of lipopolysaccharides (LPS), which increases cholesterol synthesis and raises blood cholesterol. In addition, this review will explore the natural constituents in foods with potential roles in cholesterol regulation, mainly through their interactions with the gut microbiota. These include polysaccharides, polyphenolic entities, polyunsaturated fatty acids, phytosterols, and dicaffeoylquinic acid. These findings will provide a scientific foundation for targeting hypercholesterolemia and cardiovascular diseases through the modulation of the gut microbiota.

ObjectiveThis study aimed to investigate the role of ficolin-2 (FCN2) in the development and course of hepatocellular carcinoma (HCC) and to contribute to the evolution of innovative HCC therapeutics.MethodsOncomine, GEPIA (Gene Expression Profiling Interactive Analysis), TISIDB (Tumor Immune System Interactions and Drug Bank database), UALCAN (University of Alabama at Birmingham Cancer data analysis portal), UCSC (University of California, Santa Cruz), R package, the Kaplan–Meier technique, Cox regression analysis, LinkedOmics, Pearson’s correlation, and a nomogram were used to investigate the prognostic value of FCN2 in HCC. Co-expressed genes were screened. A protein–protein interaction network was created using the STRING database. Finally, immunohistochemistry was performed to establish the expression of FCN2 in HCC tissues. A pan-cancer study centered on HCC-related molecular analysis was also conducted to look for a link between FCN2 and immune infiltration, immune modulators, and chemokine receptors.ResultsIn HCC tissues, the expression of FCN2 was observed to be lower than that in normal tissues. This was connected to the HCC marker alpha-fetoprotein, showing that FCN2 is involved in the development and progression of cancer. FCN2 may act through Staphylococcus aureus infection, lectins, and other pathways. Furthermore, at the immune level, the expression of FCN2 in HCC was associated with some immune cell infiltration, immunomodulators, and chemokine receptors.ConclusionFCN2 may be an immune checkpoint inhibitor for HCC, creating a breakthrough in the treatment of HCC.

Abstract Background Trimethylamine-N-oxide (TMAO) is an independent risk factor for atherosclerosis. Consumption of hawthorn fruit is believed to be cardio-protective, yet whether it is able to suppress the TMAO-induced atherosclerosis remains unexplored. The present study was to investigate the effects of hawthorn fruit extract (HFE) on TMAO-exacerbated atherogenesis. Methods Five groups of male Apolipoprotein E knock-out (ApoE−/−) mice were fed a low-fat diet (LFD), a Western high-fat diet (WD), or one of the three WDs containing 0.2% TMAO (WD + TMAO), 0.2% TMAO plus 1% HFE (WD + TMAO + L-HFE), or 0.2% TMAO plus 2% HFE (WD + TMAO + H-HFE), respectively. After 12-weeks of intervention, plasma levels of TMAO, lipid profile, inflammatory biomarkers, and antioxidant enzyme activities were measured. Atherosclerotic lesions in the thoracic aorta and aortic sinus were evaluated. The sterols and fatty acids in the liver and feces were extracted and measured. Hepatic expressions of inflammatory biomarkers and antioxidant enzymes were analyzed. Results Dietary TMAO accelerated atherogenesis, exacerbated inflammation, and reduced antioxidant capacities in the plasma and the liver. TMAO promoted hepatic cholesterol accumulation by inhibiting fecal excretion of acidic sterols. HFE could dose-dependently reduce the TMAO-aggravated atherosclerosis and inflammation. HFE was also able to reverse the TMAO-induced reduction in antioxidant capacity by up-regulating the expression of antioxidant enzymes including superoxide dismutase 1 (SOD1), SOD2, glutathione peroxidase 3 (GSH-Px3), and catalase (CAT) in the liver. Moreover, the hepatic cholesterol content was lowered by HFE via enhanced fecal excretion of neutral and acidic sterols. Conclusions The present results indicated that HFE was able to reduce the TMAO-exacerbated atherogenesis by attenuating inflammation and improving antioxidant capacity at least in mice. Graphic abstract

Repeated reuse of frying oil raises health concerns due to the accumulation of oxidative products after each frying cycle. Gut microbiota is integral in lipid metabolism and immune regulation. The present study was designed to investigate the effects of thermally-oxidized corn oil and lard on gut microbiota in relation to atherosclerosis, inflammatory cytokines, and plasma lipids. Male Golden Syrian hamsters were randomly divided into four groups and fed one of four diets containing fresh corn oil (CF), oxidized corn oil (CO), fresh lard (LF), and oxidized lard (LO), for six weeks. CO and LO were prepared by deep-frying potatoes in corn oil or lard for seven days. Results indicated that oxidized oil and lard caused the loss of species diversity and richness of gut microbiota. Feeding CO and LO also reduced the body and adipose tissue weights, associated with genus Acetatifactor and Allobaculum. Plasma triacylglycerols significantly increased by 51% in the CO and 35% in the LO group compared with that in their CF and LF counterparts, respectively. CO could also affect the abundance of specific bacteria genera: Bacteroides, Barnesiella, Acetatifactor, Allobaculum, Clostridium_IV, Clostridium_XIVa, Coprococcus, Lactococcus, Paraprevotella, Parasutterella, and Oscillibacter. In addition, CO and LO could adversely remodel gut composition and affect intestinal production of short-chain fatty acids, pro-inflammatory biomarkers (LPS and IL-6), anti-inflammatory biomarker IL-10, and atherosclerotic progression. It was concluded that frying oil could adversely modulate the gut microbiota and exacerbate the atherosclerosis at least in a hypercholesterolemia hamster model.

Trimethylamine-N-oxide (TMAO) has recently been identified as an independent risk factor for atherosclerosis. The present study was to investigate the effects of ginger extract (GE) on plasma cholesterol and inflammation in TMAO-exacerbated hypercholesterolemic mice. Forty-five mice were assigned into five groups and fed a non-cholesterol diet, a high-cholesterol diet, or one of the three experimental high-cholesterol diets containing 1% GE, 0.2% TMAO, or 0.2% TMAO plus 1% GE for 12 weeks. Results showed that dietary TMAO increased plasma total cholesterol (TC). GE decreased plasma TC in both non-TMAO-fed and TMAO-fed mice, by up-regulating the expression of hepatic cholesterol 7α-hydroxylase (CYP7A1) and promoting fecal excretion of total acidic sterols. GE also lowered plasma levels of proinflammatory cytokines including interleukin (IL)-1β, IL-6, tumor necrosis factor α (TNF-α), and monocyte chemotactic protein 1 (MCP-1). It was concluded that GE could alleviate the TMAO-aggravated elevation in plasma TC and vascular inflammation in high cholesterol diet-fed mice.

Piperine is the major pungent ingredient in black and white peppers. The present study investigated plasma cholesterol-lowering activity of piperine and associated underlying mechanism in hypercholesterolemia hamsters. Thirty-two hamsters were assigned into four groups receiving one of four diets namely a non-cholesterol diet (NCD), a high-cholesterol diet (HCD), and the two HCD diets containing 0.03% (PL) and 0.06% (PH) piperine, respectively, for 6 weeks. Results showed that PL and PH diets significantly reduced plasma total cholesterol (TC) by 16–17%, and non-high-density lipoprotein cholesterol (non-HDL-C) by 24–25%, respectively. This was accompanied by 84–109% increase in fecal excretion of neutral sterols with down-regulation on gene expression of intestinal Niemann-Pick C1-like 1 protein (NPC1L1), acyl-CoA:cholesterol acyltransferase 2 (ACAT2), and microsomal triacylglycerol transport protein (MTP). It was concluded that plasma TC-lowering activity of piperine was mediated by reducing the intestinal cholesterol absorption via inhibition on gene expression of intestinal NPC1L1, ACAT and MTP.

7S protein is one of four major storage proteins in soybean. The present study compared the relative cholesterol-lowering activity of the 7S protein with that of total soybean protein isolate (SPI). Forty-eight hamsters were divided into six groups fed non-cholesterol diet or one of five high-cholesterol diets containing 24.2% casein, 12.1–24.2% SPI, 12.1–24.2% 7S protein, respectively. Results showed the 7S protein reduced plasma total cholesterol (TC) by 20–41% while SPI reduced it by 9–16%. 7S protein increased the fecal excretion of neutral sterols by 43–116%, while SPI only had 18–68% increase. 7S protein increased the excretion of total bile acids by 208–367%, while SPI only increased it by 41–86%. 7S protein could not only down regulate gene expression of HMG-CoA reductase but also up regulate gene expression of CYP7A1. It was concluded that dietary 7S protein was more hypocholesterolemic than SPI, mediated by increasing the sterol excretion and decreasing the cholesterol synthesis.

Rutin (R) and quercetin (Q) are two widespread dietary flavonoids. Previous studies regarding the plasma cholesterol-lowering activity of R and Q generated inconsistent results. The present study was therefore carried out to investigate the effects of R and Q on cholesterol metabolism in both HepG2 cells and hypercholesterolemia hamsters. Results from HepG2 cell experiments demonstrate that both R and Q decreased cholesterol at doses of 5 and 10 µM. R and Q up-regulated both the mRNA and protein expression of sterol regulatory element binding protein 2 (SREBP2), low-density lipoprotein receptor (LDLR), and liver X receptor alpha (LXRα). The immunofluorescence study revealed that R and Q increased the LDLR expression, while only Q improved LDL-C uptake in HepG2 cells. Results from hypercholesterolemia hamsters fed diets containing R (5.5 g/kg diet) and Q (2.5 g/kg diet) for 8 weeks demonstrate that both R and Q had no effect on plasma total cholesterol. In the liver, only Q reduced cholesterol significantly. The discrepancy between the in vitro and in vivo studies was probably due to a poor bioavailability of flavonoids in the intestine. It was therefore concluded that R and Q were effective in reducing cholesterol in HepG2 cells in vitro, whereas in vivo, the oral administration of the two flavonoids had little effect on plasma cholesterol in hamsters.

β-Sitosterol (SI) is hypocholesterolemic. The present study investigated whether the blockage of its hydroxyl group would abolish its cholesterol-lowering activity. The blockage was made by methylating and ethylating the hydroxyl group on C3 position, leading to formation of β-sitosteryl 3β-methoxy (SM) and β-sitosteryl 3β-ethoxy (SE) derivatives. Male hamsters were divided into five groups (n = 8 each) and fed the non-cholesterol diet (NCD), high cholesterol diet containing 5 mmol of cholesterol (HCD), or one of the three high cholesterol experimental diets with addition of 5 mmol of SI (HCD + SI), 5 mmol of SM (HCD + SM) and 5 mmol of SE (HCD + SE), respectively, for 8 weeks. Results showed that SI could significantly reduce plasma total cholesterol (TC) by 17% (P

Interest in Tartary buckwheat as a cholesterol-lowering functional food is increasing. The present study was to (i) investigate the relative hypocholesterolemic activity of Tartary buckwheat flour compared with that of wheat and rice flour; and (ii) study the interaction of these three flours with gene expression of sterol transporters and proteins involved in cholesterol absorption. Thirty-six male hamsters were divided into four groups fed either the control or one of three experimental diets containing 24% respective flour, for a period of 6 weeks. Results showed that Tartary buckwheat flour but no wheat and rice flours reduced plasma total cholesterol (TC) and non-high-density lipoprotein cholesterol (non-HDL) as well as hepatic cholesterol concentrations. Compared with that of wheat and rice flours, supplementation of Tartary buckwheat flour into diet led to greater neutral sterol excretion and lesser mRNA of intestinal Niemann-Pick C1 Like 1 (NPC1L1) and acyl-CoA: cholesterol acyltransferase 2 (ACAT2). It was therefore concluded that Tartary buckwheat flour was hypocholesterolemic via inhibition of cholesterol absorption, most likely mediated by down-regulation of intestinal NPC1L1 and ACAT2.

Docosahexaenoic acid (DHA) plays important roles in the prevention of ageing and ageing-related diseases. In this work, the anti-ageing effect of Schizochytrium mangrovei (SM), a marine microalga with high contents of DHA was investigated for the first time. In vitro results showed that SM enhanced the vitality of healthy pheochromocytoma (PC12) cells, whereas it had no protective effect under H2O2-induced oxidative stress. Meanwhile, SM exerted neuroprotective actions in vivo: the supplementation of SM significantly extended the lifespan of both wild type and SODn108 mutant flies Drosophila melanogaster, and ameliorated the age-related decline of locomotor function. This lifespan-extending activity was associated with the mRNA up-regulation of endogenous stress-defense genes such as CuZn-superoxide dismutase (SOD1) and Mn-superoxide dismutase (SOD2), as well as the down-regulation of Methuselah (MTH) gene. Therefore, it was concluded that the anti-ageing capability of DHA-rich SM was mediated through the cooperation with endogenous stress-defense system rather than the direct interaction with oxidative free radicals.

Cholesterol is always an issue because blood total cholesterol (TC) and low-density lipoprotein (LDL) correlate strongly with coronary heart disease. Cholesterol homeostasis is maintained by a complex mechanism of sterol absorption, anabolism, catabolism and excretion. Nutraceuticals and functional foods which lower TC must affect the genes which regulate cholesterol homeostasis. In general, cholesterol-lowering functional foods and nutraceuticals can be classified into seven types namely intestinal Niemann-Pick C1 like 1 (NPC1L1) competitors, intestinal acyl-CoA:cholesterol acyltransferase 2 (ACAT2) inhibitors, 3-hydroxy-3-methylglutaryl (HMG-CoA) reductase inhibitors, LDL receptor up-regulators, bile acid reabsorption inhibitors, cholesterol-7α-hydroxylase (CYP7A1) activators, and plasma cholesteryl ester transporting protein (CETP) inhibitors. This mini-review classifies the popular cholesterol-lowering nutraceuticals and functional foods, and explores their underlying mechanisms.

This study aimed at substantiating the associations of the apolipoproein M gene (APOM) with type 2 diabetes (T2D) as well as with metabolic traits in Hong Kong Chinese. In addition, APOM gene function was further characterized to elucidate its activity in cholesterol metabolism. Seventeen APOM SNPs documented in the NCBI database were genotyped. Five SNPs were confirmed in our study cohort of 1234 T2D and 606 control participants. Three of the five SNPs rs707921(C+1871A), rs707922(G+1837T) and rs805264(G+203A) were in linkage disequilibrium (LD). We chose rs707922 to tag this LD region for down stream association analyses and characterized the function of this SNP at molecular level. No association between APOM and T2D susceptibility was detected in our Hong Kong Chinese cohort. Interestingly, the C allele of rs805297 was significantly associated with T2D duration of longer than 10 years (OR = 1.245, p = 0.015). The rs707922 TT genotype was significantly associated with elevated plasma total- and LDL- cholesterol levels (p = 0.006 and p = 0.009, respectively) in T2D patients. Molecular analyses of rs707922 lead to the discoveries of a novel transcript APOM5 as well as the cryptic nature of exon 5 of the gene. Ectopic expression of APOM5 transcript confirmed rs707922 allele-dependent activity of the transcript in modifying cholesterol homeostasis in vitro. In conclusion, the results here did not support APOM as a T2D susceptibility gene in Hong Kong Chinese. However, in T2D patients, a subset of APOM SNPs was associated with disease duration and metabolic traits. Further molecular analysis proved the functional activity of rs707922 in APOM expression and in regulation of cellular cholesterol content.