China
Africa
Explore chapters and articles related to this topic
Gene–Diet Interactions
Published in Nathalie Bergeron, Patty W. Siri-Tarino, George A. Bray, Ronald M. Krauss, Nutrition and Cardiometabolic Health, 2017
Silvia Berciano, Jose M. Ordovas, Nathalie Bergeron, Patty W. Siri-Tarino, George A. Bray, Ronald M. Krauss
Another example of replicated evidence without support from GWAS findings comes from the apolipoprotein A2 (APOA2) gene and its relation to obesity. We have identified and replicated a significant interaction between the APOA2 gene variant [APOA2-265T > C (rs5082)] (which in vitro has been shown to modulate APOA2 gene expression), dietary SFAs, and BMI. We analyzed gene–diet interactions between the rs5082 SNP and SFA intake on BMI and obesity in subjects from three American populations: (1) Framingham Heart Study (1454 Whites); (2) GOLDN (1078 Whites); and (3) BPRHS (930 Hispanics of Caribbean origin). We found that the magnitude of the difference in BMI between the homozygotes for the risk allele C and carriers of the major allele was dependent on SFA intake. We observed a difference of 6.2% in BMI between the two genotype groups when SFA consumption was high (>22 g/d), but no difference when SFA consumption was low. Moreover, the CC genotype was significantly associated with higher obesity prevalence in these populations only when SFA intake was high (Corella et al., 2009b). These findings in three independent populations were further replicated in other geographical areas and ethnic groups (Corella et al., 2011b), and more recently, we replicated these interactions using specific foods (i.e., dairy) (Smith et al., 2013).
Plasma lipids and lipoproteins
Published in Martin Andrew Crook, Clinical Biochemistry & Metabolic Medicine, 2013
The proteins associated with lipoproteins are called apolipoproteins (apo). ApoA (mainly apoA1 and apoA2) is the major group associated with HDL particles. The apoB series (apoB100) is predominantly found with LDL particles and is the ligand for the LDL receptor. Low-density lipoprotein has one molecule of apoB100
Mechanisms of Fibril Formation and Cellular Response
Published in Martha Skinner, John L. Berk, Lawreen H. Connors, David C. Seldin, XIth International Symposium on Amyloidosis, 2007
Martha Skinner, John L. Berk, Lawreen H. Connors, David C. Seldin
high-level expression of Apoa2c mRNA was found in the testis, liver, brain, kidney, heart, lungs, spleen, stomach and intestine by RT-PCR. However it was detected only in the liver, brain, lung and stomach of Tg-/-mice. Quantitation of plasma apoA-I and apoA-II levels revealed that the concentration of apoA-II in Tg+/+ mice, was 1.57-fold greater than in Tg-/- mice (P < 0.05). Total and HDL cholesterol levels were significantly (P < 0.05) increased in Tg+/+ mice compared to Tg-/- mice. To induce amyloidosis, sonicated AApoAII
Macrophages in the reticuloendothelial system inhibit early induction stages of mouse apolipoprotein A-II amyloidosis
Published in Amyloid, 2023
Hiroki Miyahara, Jian Dai, Ying Li, Xiaoran Cui, Hibiki Takeuchi, Naomi Hachiya, Fuyuki Kametani, Masahide Yazaki, Masayuki Mori, Keiichi Higuchi
To address these issues, we investigated phagocyte-related amyloid clearance mechanisms using an inducible mouse AApoAII amyloidosis model. AApoAII amyloidosis is characterized by systemic amyloid deposition derived from circulating apolipoprotein A-II (ApoA-II), which is a secondary abundant apoprotein of high-density lipoproteins (HDL). In humans, 4 different point mutations, all of which are located in the stop codon of the APOA2 gene, resulted in variant ApoA-II with a C-terminal 21-residue elongation [20–22]. Additionally, one case of wild-type ApoA-II-derived amyloidosis has been reported [23]. In mice, AApoAII amyloidosis was initially detected in a senescence accelerated-mouse prone (SAMP1) model [24]. We subsequently reported that laboratory inbred strain C57BL/6 and crossbred strain BDF1 mice spontaneously developed AApoAII amyloidosis with aging [25]. There are seven alleles of the Apoa2 gene among inbred laboratory strains, and the mouse strain with the type C allele of Apoa2 (Apoa2c) exhibits accelerated spontaneous AApoAII amyloidosis [26]. We established a congenic strain of mice with the amyloidogenic Apoa2c allele on the genetic background of the senescence-accelerated resistant mouse (SAMR1), named R1.P1-Apoa2c [27]. The lag phase of AApoAII progression in R1.P1-Apoa2 mice may be markedly shortened by the administration of a tissue-extracted AApoAII fibril fraction [27]. Therefore, R1.P1-Apoa2c mice represent a valid model for elucidating the cellular and molecular mechanisms of action of phagocytes in both the transmission and progression of amyloidosis.
Quantifying HDL proteins by mass spectrometry: how many proteins are there and what are their functions?
Published in Expert Review of Proteomics, 2018
HDL is a family of nanoparticles composed of non-covalently associated amphipathic lipids, neutral lipids, and proteins that undergo complex metabolic interactions with other classes of lipoproteins, cells, and plasma proteins [16]. Its major proteins, apolipoprotein A-I (APOA1) and APOA2, account for ~70% and ~20% of its protein mass [17,18] and over half the mass of the lipoprotein. However, it is not a homogeneous population of particles because the lipoproteins vary greatly in protein composition and size, consisting of multiple subspecies that vary from 7 to 14 nm in diameter. Moreover, shotgun proteomics has revealed that HDL carries a wide array of proteins linked to inflammation, complement regulation, and proteolysis inhibition (Figure 1) [19]. As HDL-C measurements do not reflect the abundance of such proteins [20], modulating HDL-C levels might have no impact on the properties of the particular particles responsible for atheroprotection [6,21]. Indeed, elevating HDL-C levels with drugs that act by different mechanisms has not lowered CVD risk in statin-treated humans with established atherosclerosis [22–24]. For example, torcetrapib, a potent cholesteryl ester transfer protein (CETP) inhibitor, inhibited the development of atherosclerosis in rabbits [25] and also increased HDL-C by 60–100% in early-phase human studies [26,27]. However, several large trials with torcetrapib showed no clinical benefits, as rates of CVD and total death were higher in the treated group than in the controls [22,28,29]. Another trial with a combination of niacin and statin also failed to reduce the risk of cardiovascular events due to no incremental clinical benefit and a twofold increase in stroke risk [30].
Trends in biomarker discoveries for the early detection and risk stratification of pancreatic cancer using omics studies
Published in Expert Review of Molecular Diagnostics, 2019
Takashi Kobayashi, Kazufumi Honda
We recently identified plasma/serum apolipoprotein A2 (apoA2) isoforms, which are among the promising proteomic biomarkers for early PDAC and at-risk diseases. ApoA2 is a major component of high-density lipoproteins (HDLs), and plays an important role in directing the fate of lipid metabolism among HDLs. In humans, most circulating apoA2 exists as a homodimer comprising two identical 77-residue polypeptide chains linked by a disulfide bridge between Cys-6 residues. Five isoforms of apoA2 have been identified, showing different amino acid sequences in the C-terminal region: apoA2-ATQ/ATQ, apoA2-ATQ/AT, apoA2-AT/AT, apoA2-AT/A, and apoA2-A/A. In recent years, proteomic approaches have revealed that levels of specific apoA2 isoforms in the serum/plasma of pancreatic cancer patients differ significantly from those seen in healthy individuals, even in the early stages of the disease [24]. A significant reduction in apoA2-ATQ/AT was detected in the plasma of any stage of PDAC. Areas under the curve (AUCs) to differentiate stage I, II, III and IV were 0.939, 0.957, 0.926 and 0.946, respectively. A significant reduction in apoA2-ATQ/AT has also been detected in at-risk diseases for PDAC, such as IPMN and chronic pancreatitis. Those findings were confirmed in a blinded study of a pancreatic cancer reference sample set organized by the National Cancer Institute Early Detection Research Network (NCI EDRN). In this blinded study, AUCs for CA19-9 and apoA2-ATQ/AT as single biomarkers to distinguish patients with early-stage pancreatic cancer (stage-I/II) were 0.783 (95% confidence interval (CI), 0.699–0.855) and 0.809 (95%CI, 0.748–0.867), respectively [25]. In addition, plasma samples collected by the European Prospective Investigation into Cancer and Nutrition study have been investigated, revealing that combination assay with CA19-9 and apoA2-ATQ/AT enabled earlier detection of PDAC than CA19-9 alone up to 18 months before diagnosis [26]. Such findings suggest apoA2 isoforms as potential biomarkers for filtering the general population for individuals at higher risk of PDAC. Although the mechanisms underlying these findings are still unknown, we have previously reported that specific abnormal processing patterns of amino acid in the C-terminal ends of apoA2 homodimer were observed in PDAC or autoimmune pancreatitis (AIP) [27,28]. Hayasaki et al. recently reported that apoA2-ATQ levels seem to reflect pancreatic atrophy and insufficient secretion of circulating pancreatic enzymes, and could provide a biomarker to assess pancreatic exocrine disorder [29].