Genomes and Genes
Gene Symbol: Apoc3
Description: apolipoprotein C3
Alias: ApoC-III, apo-CIII, apolipoprotein C-III, apolipoprotein C-3
- Windler E, Havel R. Inhibitory effects of C apolipoproteins from rats and humans on the uptake of triglyceride-rich lipoproteins and their remnants by the perfused rat liver. J Lipid Res. 1985;26:556-65 pubmed..Preferential loss of apolipoprotein C-II during remnant formation may regulate the termination of triglyceride hydrolysis prior to complete removal of triglycerides from chylomicrons and VLDL. ..
- Dashti N, Ontko J. Alterations in rat serum lipids and apolipoproteins following clofibrate treatment. Atherosclerosis. 1983;49:255-66 pubmed..These observations suggest that the hypolipidemic effect of clofibrate in the normolipemic rat is caused mainly by diminished hepatic secretion, rather than by enhanced catabolism, of triglyceride-rich lipoproteins. ..
- Hughes T, Gaber A, Amiri H, Wang X, Elmer D, Winsett R, et al. Lipoprotein composition in insulin-dependent diabetes mellitus with chronic renal failure: effect of kidney and pancreas transplantation. Metabolism. 1994;43:333-47 pubmed..The addition of a pancreas to a kidney transplant had no obvious impact on the lipoproteins.(ABSTRACT TRUNCATED AT 400 WORDS)..
- Rodrigo E, Gonzalez Lamuno D, Ruiz J, Fresnedo G, Isla D, Cotorruelo J, et al. Association between the SstI polymorphism of the apolipoprotein C-III gene, glucose intolerance and cardiovascular risk in renal transplant recipients. Transplant Proc. 2002;34:379 pubmed
- Florez H, Mendez A, Casanova Romero P, Larreal Urdaneta C, Castillo Florez S, Lee D, et al. Increased apolipoprotein C-III levels associated with insulin resistance contribute to dyslipidemia in normoglycemic and diabetic subjects from a triethnic population. Atherosclerosis. 2006;188:134-41 pubmed..52, P < 0.01). These results suggest that higher apo C-III may contribute to the increased cardiovascular risk in subjects with insulin resistance and type 2 diabetes through its effects on triglycerides and LDL particle size. ..
- Wang C, McConathy W, Kloer H, Alaupovic P. Modulation of lipoprotein lipase activity by apolipoproteins. Effect of apolipoprotein C-III. J Clin Invest. 1985;75:384-90 pubmed....
- Hallman D, Srinivasan S, Chen W, Boerwinkle E, Berenson G. Longitudinal analysis of haplotypes and polymorphisms of the APOA5 and APOC3 genes associated with variation in serum triglyceride levels: the Bogalusa Heart Study. Metabolism. 2006;55:1574-81 pubmedPolymorphisms in the APOC3 and APOA5 genes, from the APOA1/APOC3/APOA4/APOA5 gene cluster on chromosome 11q23, have been associated with interindividual variation in plasma triglycerides...
- Caron S, Verrijken A, Mertens I, Samanez C, Mautino G, Haas J, et al. Transcriptional activation of apolipoprotein CIII expression by glucose may contribute to diabetic dyslipidemia. Arterioscler Thromb Vasc Biol. 2011;31:513-9 pubmed publisher..Glucose induces apoCIII transcription, which may represent a mechanism linking hyperglycemia, hypertriglyceridemia, and cardiovascular disease in type 2 diabetes. ..
- Berbee J, van der Hoogt C, Sundararaman D, Havekes L, Rensen P. Severe hypertriglyceridemia in human APOC1 transgenic mice is caused by apoC-I-induced inhibition of LPL. J Lipid Res. 2005;46:297-306 pubmed..Therefore, we conclude that apoC-I is a potent inhibitor of LPL-mediated TG-lipolysis. ..
- Dallongeville J, Cottel D, Montaye M, Codron V, Amouyel P, Helbecque N. Impact of APOA5/A4/C3 genetic polymorphisms on lipid variables and cardiovascular disease risk in French men. Int J Cardiol. 2006;106:152-6 pubmed..The APOA5 S19W, APOA5 -l2,238T>C, APOA4 T347S and APOC3 -482C>T SNPs were examined. The APOA5 S19W polymorphism was associated with plasma triglyceride levels...
- Singh P, Singh M, Gaur S, Kaur T. The ApoAI-CIII-AIV gene cluster and its relation to lipid levels in type 2 diabetes mellitus and coronary heart disease: determination of a novel susceptible haplotype. Diab Vasc Dis Res. 2007;4:124-9 pubmed..45) even after adjustment for confounders. The findings in the present study suggest that each unit of P1-S2-X1 in diabetes increases the risk of CHD by a factor of 1.37+/-0.307 (beta + SE), which is manifest in its multiplicative mode. ..
- Smith C, Tucker K, Scott T, Van Rompay M, Mattei J, Lai C, et al. Apolipoprotein C3 polymorphisms, cognitive function and diabetes in Caribbean origin Hispanics. PLoS ONE. 2009;4:e5465 pubmed publisherApolipoprotein C3 (APOC3) modulates triglyceride metabolism through inhibition of lipoprotein lipase, but is itself regulated by insulin, so that APOC3 represents a potential mechanism by which glucose metabolism may affect lipid ..
- Kypreos K. ABCA1 promotes the de novo biogenesis of apolipoprotein CIII-containing HDL particles in vivo and modulates the severity of apolipoprotein CIII-induced hypertriglyceridemia. Biochemistry. 2008;47:10491-502 pubmed publisher..Furthermore, the data establish that ABCA1 and apoCIII-containing HDL play key roles in the prevention of apoCIII-induced hypertriglyceridemia in mice. ..
- Jong M, Rensen P, Dahlmans V, van der Boom H, van Berkel T, Havekes L. Apolipoprotein C-III deficiency accelerates triglyceride hydrolysis by lipoprotein lipase in wild-type and apoE knockout mice. J Lipid Res. 2001;42:1578-85 pubmedPrevious studies with hypertriglyceridemic APOC3 transgenic mice have suggested that apolipoprotein C-III (apoC-III) may inhibit either the apoE-mediated hepatic uptake of TG-rich lipoproteins and/or the lipoprotein lipase (LPL)-mediated ..
- Mancone C, Amicone L, Fimia G, Bravo E, Piacentini M, Tripodi M, et al. Proteomic analysis of human very low-density lipoprotein by two-dimensional gel electrophoresis and MALDI-TOF/TOF. Proteomics. 2007;7:143-54 pubmed..While the physiological relevance of our finding remains to be assessed, we believe that our results will be useful as reference for future studies of VLDL structure in specific physiopathological conditions. ..
- Miller M, Rhyne J, Chen H, Beach V, Ericson R, Luthra K, et al. APOC3 promoter polymorphisms C-482T and T-455C are associated with the metabolic syndrome. Arch Med Res. 2007;38:444-51 pubmed..One candidate, APOC3, modulates lipid and lipoprotein metabolism and the promoter polymorphisms C-482T/T-455C are associated with loss ..
- Ceccarelli V, Nocentini G, Riccardi C, Ayroldi E, Di Nardo P, Roberti R, et al. Effect of dietary saturated fatty acids on HNF-4α DNA binding activity and ApoCIII mRNA in sedentary rat liver. Mol Cell Biochem. 2011;347:29-39 pubmed publisher..In conclusion, we can speculate that dietary saturated fats, acting at apolipoprotein transcriptional level, may impact on the close relationship existing among high ApoCIII plasma level, dyslipidemia, and atherosclerosis. ..
- Blaufuss M, Gordon J, Schonfeld G, Strauss A, Alpers D. Biosynthesis of apolipoprotein C-III in rat liver and small intestinal mucosa. J Biol Chem. 1984;259:2452-6 pubmed..Thus, the acute response of the apo-A-I and C-III genes to triacylglycerol absorption differs. ..
- Nofer J, Remaley A, Feuerborn R, Wolinnska I, Engel T, von Eckardstein A, et al. Apolipoprotein A-I activates Cdc42 signaling through the ABCA1 transporter. J Lipid Res. 2006;47:794-803 pubmed..We conclude that ABCA1 transduces signals from apoA-I by complexing and activating Cdc42 and downstream kinases and, therefore, acts as a full apoA-I receptor...
- Tanaka S, Tamura K, Mizuno Y. [Clinical consideration with special reference to autopsy cases of malignant tumor in the oral cavity, treated with Bleomycin (author's transl)]. Hiroshima Daigaku Shigaku Zasshi. 1975;8:168-75 pubmed
- Joven J, Villabona C, Vilella E. Pattern of hyperlipoproteinemia in human nephrotic syndrome: influence of renal failure and diabetes mellitus. Nephron. 1993;64:565-9 pubmed....
- Morgan P, Sturgess A, Hennessy A, Davies M. Serum protein oxidation and apolipoprotein CIII levels in people with systemic lupus erythematosus with and without nephritis. Free Radic Res. 2007;41:1301-12 pubmed..Total apoCIII levels (assessed by ELISA) in lupus nephritis patients were significantly elevated compared to controls or non-renal SLE patients. Thus, levels of oxidized proteins and apoCIII may be useful biomarkers in SLE studies. ..
- al Muhtaseb N, al Yousuf A, Bajaj J. Apolipoprotein A-I, A-II, B, C-II, and C-III in children with insulin-dependent diabetes mellitus. Pediatrics. 1992;89:936-41 pubmed..We suggest that measurement of apo C-III level along with apo B and apo A-I in these patients may be a sensitive indicator to alterations in glycemic control. ..
- Connelly P, Maguire G, Vezina C, Hegele R, Little J. Identification of disulfide-linked apolipoprotein species in human lipoproteins. J Lipid Res. 1993;34:1717-27 pubmed..These results demonstrate that the molecular species of cysteine-containing apolipoproteins are complex and should be considered in studies of human lipoprotein composition and function. ..
- Kim J, Park H, Choi I, Kim Y, Cho K. Severely modified lipoprotein properties without a change in cholesteryl ester transfer protein activity in patients with acute renal failure secondary to Hantaan virus infection. BMB Rep. 2010;43:535-40 pubmed..Low-density lipoprotein (LDL) particle size was smaller and the distribution was less homogeneous. Patients with HFRS in the oliguric phase had severely modified lipoproteins in composition and metabolism. ..
- Dorfmeister B, Zeng W, Dichlberger A, Nilsson S, Schaap F, Hubacek J, et al. Effects of six APOA5 variants, identified in patients with severe hypertriglyceridemia, on in vitro lipoprotein lipase activity and receptor binding. Arterioscler Thromb Vasc Biol. 2008;28:1866-71 pubmed publisher..Their occurrence in the homozygous state, coinheritance of LPL variants or common APOA5 TG-raising variant in trans, appears to be essential for their phenotypic expression. ..
- Henderson H, Landon S, Michie J, Berger G. Association of a DNA polymorphism in the apolipoprotein C-III gene with diverse hyperlipidaemic phenotypes. Hum Genet. 1987;75:62-5 pubmed..These results suggest that the Sst-1 site is linked to a gene defect with a minor or subtle phenotypic effect which enhances the expression of a co-existent major monogenic defect of lipoprotein transport. ..
- Shen P, Howlett G. Alteration in rat apolipoprotein C-III gene expression and lipoprotein composition during inflammation. Inflammation. 1993;17:153-66 pubmed..A decrease in the concentration of apo A-I-containing HDL particles was also observed in these rats. The results indicate altered apolipoprotein gene expression associated with alterations in the size and composition of HDL particles. ..
- Wang J, Wang L, Zhang D, Fan Y, Jia Z, Qin P, et al. Identification of potential serum biomarkers for Wilms tumor after excluding confounding effects of common systemic inflammatory factors. Mol Biol Rep. 2012;39:5095-104 pubmed publisher..Taken together, these findings suggest that SAA1 and APO C-III are two potential biomarkers for Wilms tumor. ..
- Duivenvoorden I, Teusink B, Rensen P, Romijn J, Havekes L, Voshol P. Apolipoprotein C3 deficiency results in diet-induced obesity and aggravated insulin resistance in mice. Diabetes. 2005;54:664-71 pubmed..b>Apoc3(-/-) mice and wild-type littermates were fed a high-fat (46 energy %) diet for 20 weeks...
- Lin Lee Y, Strobl W, Soyal S, Radosavljevic M, Song M, Gotto A, et al. Role of thyroid hormone in the expression of apolipoprotein A-IV and C-III genes in rat liver. J Lipid Res. 1993;34:249-59 pubmed....
- Ooi E, Chan D, Watts G, Chan D, Ng T, Dogra G, et al. Plasma apolipoprotein C-III metabolism in patients with chronic kidney disease. J Lipid Res. 2011;52:794-800 pubmed publisher..05 for all). Altered plasma apoC-III metabolism is a feature of dyslipidemia in moderate CKD. Modification of apoC-III catabolism may be an important therapeutic target for reducing cardiovascular disease risk in moderate CKD. ..
- Jackson K, Wolstencroft E, Bateman P, Yaqoob P, Williams C. Apolipoprotein E enrichment of immuno-separated chylomicron and chylomicron remnants following saturated fatty acids. Nutr Metab Cardiovasc Dis. 2006;16:405-17 pubmed....
- Sedova L, Seda O, Krenova D, Kren V, Kazdova L. Isotretinoin and fenofibrate induce adiposity with distinct effect on metabolic profile in a rat model of the insulin resistance syndrome. Int J Obes Relat Metab Disord. 2004;28:719-25 pubmed..The PD/Cub strain may also serve as a pharmacogenetic model for dissection of the retinoid-induced hypertriglyceridemia. ..
- Takahashi H, Hashimoto N, Kawasaki T, Kikuchi T, Uchiyama M. The usefulness of measuring body fat deposition for detecting obesity and atherogenesity in Japanese school children. Acta Paediatr Jpn. 1996;38:634-9 pubmed..lipoprotein cholesterol (LDL-C), atherogenic index (AI), RLP-cholesterol (RLP-C), apoA1, apoA2, apoB, apoC2, apoC3, apoE and the ratio of apoB to apoA1 than non-overweight boys...
- Kee F, Amouyel P, Fumeron F, Arveiler D, Cambou J, Evans A, et al. Lack of association between genetic variations of apo A-I-C-III-A-IV gene cluster and myocardial infarction in a sample of European male: ECTIM study. Atherosclerosis. 1999;145:187-95 pubmed..In conclusion, in the ECTIM study, the apo A-I, C-III, A-IV gene cluster polymorphism is associated with neither circulating plasma variables nor MI survival. ..
- Huard K, Bourgeois P, Rhainds D, Falstrault L, Cohn J, Brissette L. Apolipoproteins C-II and C-III inhibit selective uptake of low- and high-density lipoprotein cholesteryl esters in HepG2 cells. Int J Biochem Cell Biol. 2005;37:1308-18 pubmed..These results indicate that apoC-II and apoC-III inhibit CE-selective uptake. ..
- Maeda N, Li H, Lee D, Oliver P, Quarfordt S, Osada J. Targeted disruption of the apolipoprotein C-III gene in mice results in hypotriglyceridemia and protection from postprandial hypertriglyceridemia. J Biol Chem. 1994;269:23610-6 pubmed..These data indicate that ApoC-III modulates the catabolism of triglyceride-rich lipoproteins and plays a role in the postprandial management of triglycerides. ..
- Sehayek E, Eisenberg S. Mechanisms of inhibition by apolipoprotein C of apolipoprotein E-dependent cellular metabolism of human triglyceride-rich lipoproteins through the low density lipoprotein receptor pathway. J Biol Chem. 1991;266:18259-67 pubmed....
- Graham M, Lee R, Bell T, Fu W, Mullick A, Alexander V, et al. Antisense oligonucleotide inhibition of apolipoprotein C-III reduces plasma triglycerides in rodents, nonhuman primates, and humans. Circ Res. 2013;112:1479-90 pubmed publisher..This compelling pharmacological profile supports further clinical investigations in hypertriglyceridemic subjects. ..
- Inoue T, Kawaji T, Tanihara H. Elevated levels of multiple biomarkers of Alzheimer's disease in the aqueous humor of eyes with open-angle glaucoma. Invest Ophthalmol Vis Sci. 2013;54:5353-8 pubmed publisher..To investigate levels of biomarkers of Alzheimer's disease in the aqueous humor in patients with open-angle glaucoma (OAG)...
- Andersson Y, Majd Z, Lefebvre A, Martin G, Sechkin A, Kosykh V, et al. Developmental and pharmacological regulation of apolipoprotein C-II gene expression. Comparison with apo C-I and apo C-III gene regulation. Arterioscler Thromb Vasc Biol. 1999;19:115-21 pubmed....
- Remaley A, Stonik J, Demosky S, Neufeld E, Bocharov A, Vishnyakova T, et al. Apolipoprotein specificity for lipid efflux by the human ABCAI transporter. Biochem Biophys Res Commun. 2001;280:818-23 pubmed..In summary, ABCAI-mediated cellular binding of apolipoproteins and lipid efflux is not specific for only apoA-I but can also occur with other apolipoproteins that contain multiple amphipathic helical domains...
- Dallinga Thie G, van Linde Sibenius Trip M, Rotter J, Cantor R, Bu X, Lusis A, et al. Complex genetic contribution of the Apo AI-CIII-AIV gene cluster to familial combined hyperlipidemia. Identification of different susceptibility haplotypes. J Clin Invest. 1997;99:953-61 pubmed..XmnI, and MspI sites 5' of the apo AI gene and SstI site in the 3' untranslated region of exon 4 of the apo CIII gene in 18 FCH pedigrees, including 18 probands, 178 hyperlipidemic relatives, 210 normolipidemic relatives, and ..
- Howell M, Li R, Zhang R, Li Y, Chen W, Chen G. The expression of Apoc3 mRNA is regulated by HNF4α and COUP-TFII, but not acute retinoid treatments, in primary rat hepatocytes and hepatoma cells. Mol Cell Biochem. 2014;387:241-50 pubmed..The Rarb and Srebp-1c mRNA levels are higher in the liver and isolated hepatocytes from ZF than ZL rats. The Apoc3 mRNA level is only higher in the isolated hepatocytes from ZF than ZL rats...
- Schoonjans K, Peinado Onsurbe J, Fruchart J, Tailleux A, Fievet C, Auwerx J. 3-Hydroxy-3-methylglutaryl CoA reductase inhibitors reduce serum triglyceride levels through modulation of apolipoprotein C-III and lipoprotein lipase. FEBS Lett. 1999;452:160-4 pubmed..These results suggest that the triglyceride-lowering effect of statins involves a stimulation of lipoprotein lipase-mediated clearance of triglyceride-rich lipoproteins. ..
- Hamadneh L, Al Essa L, Hikmat S, Al Qirim T, Abu Sheikha G, Al Hiari Y, et al. N-(3-Benzoylphenyl)-1H-Indole-2-Carboxamide decreases triglyceride levels by downregulation of Apoc3 gene expression in acute hyperlipidemic rat model. Mol Cell Biochem. 2017;431:133-138 pubmed publisher..Several genes of potential interest were reported to be overexpressed by Triton WR1339 including Apoc3, Apob, Hmgcs2, Apoa1, Apoe, Apof, acsl1, and Decr1...
- Liu H, Labeur C, Xu C, Ferrell R, Lins L, Brasseur R, et al. Characterization of the lipid-binding properties and lipoprotein lipase inhibition of a novel apolipoprotein C-III variant Ala23Thr. J Lipid Res. 2000;41:1760-71 pubmedWe have identified a G-to-A transition in exon 3 of the APOC3 gene resulting in a novel Ala23Thr apolipoprotein (apo) C-III variant, associated with apoC-III deficiency in three unrelated Yucatan Indians...
- Konemori G, Kawanishi M, Nakamoto A, Hiraoka M, Kajiyama G. [Application of the box plot to evaluate serum lipid levels and apolipoprotein levels in patients with cerebral infarction and diabetes mellitus]. Nihon Ronen Igakkai Zasshi. 1990;27:22-7 pubmed..d. Compared to the control group, the ratio of LDL-C. to Apo B was lower (p less than 0.05) in the cerebral infarction group with diabetes mellitus and tended to be lower even in the diabetes mellitus-only group. ..
- Gerritsen G, Rensen P, Kypreos K, Zannis V, Havekes L, Willems van Dijk K. ApoC-III deficiency prevents hyperlipidemia induced by apoE overexpression. J Lipid Res. 2005;46:1466-73 pubmed..Because apoC-III is a strong inhibitor of TG hydrolysis, we questioned whether Apoc3 deficiency might prevent the hyperlipidemia induced by apoE overexpression in vivo...
- Kamisako T, Ogawa H. Effect of bile duct obstruction on the expression of intestinal mRNA related to cholesterol and bile acid metabolism in the rat. J Gastroenterol Hepatol. 2007;22:125-31 pubmed..The purpose of this study was to evaluate the effect of bile duct ligation (BDL) on the expression of intestinal and hepatic genes that are important for cholesterol and bile acid metabolism...
- Yokoyama S, Kawai Y, Tajima S, Yamamoto A. Behavior of human apolipoprotein E in aqueous solutions and at interfaces. J Biol Chem. 1985;260:16375-82 pubmed....
- de Messieres M, Huang R, He Y, Lee J. Amyloid triangles, squares, and loops of apolipoprotein C-III. Biochemistry. 2014;53:3261-3 pubmed publisher..Triangles and squares with a width of ~50 nm were also observed, which may be a novel form of amyloid or related to previously reported amyloid rings. ..
- Hirano T, Takahashi T, Saito S, Tajima H, Ebara T, Adachi M. Apoprotein C-III deficiency markedly stimulates triglyceride secretion in vivo: comparison with apoprotein E. Am J Physiol Endocrinol Metab. 2001;281:E665-9 pubmed..These results suggest that apo C-III deficiency potently enhances TG turnover, especially when TG production is stimulated, and that apo E deficiency is not always rate limiting for TG production...
- Holmberg R, Refai E, Höög A, Crooke R, Graham M, Olivecrona G, et al. Lowering apolipoprotein CIII delays onset of type 1 diabetes. Proc Natl Acad Sci U S A. 2011;108:10685-9 pubmed publisher..ApoCIII thus serves as a diabetogenic factor, and intervention with this apolipoprotein in the prediabetic state can arrest disease progression. These findings suggest apoCIII as a target for the treatment of type 1 diabetes. ..
- Lee D, Jackson K, Knowlton N, Wages J, Alaupovic P, Samuelsson O, et al. Oxidative stress and inflammation in renal patients and healthy subjects. PLoS ONE. 2011;6:e22360 pubmed publisher..In conclusion, we have discovered a new inflammatory factor, TG48. It is characterized with TG rich in saturated fatty acids. Renal patients have increased TG48 than healthy controls. ..
- Klein R, McHenry M, Lok K, Hunter S, Le N, Jenkins A, et al. Apolipoprotein C-III protein concentrations and gene polymorphisms in Type 1 diabetes: associations with microvascular disease complications in the DCCT/EDIC cohort. J Diabetes Complications. 2005;19:18-25 pubmed..In the DCCT/EDIC cohort of patients, there was an independent positive association of apoCIII level with microvascular complications of Type 1 diabetes. ..
- Hokanson J, Kinney G, Cheng S, Erlich H, Kretowski A, Rewers M. Susceptibility to type 1 diabetes is associated with ApoCIII gene haplotypes. Diabetes. 2006;55:834-8 pubmed..00, 0.97, and 0.73, respectively; P = 0.03). This haplotype block contains an insulin response element. Screening for this haplotype may identify at-risk individuals, and this pathway may offer a target for prevention of type 1 diabetes. ..
- Panin L, Shalbueva N, Polyakov L. Effects of apolipoproteins C on oxidative phosphorylation in rat liver mitochondria. Bull Exp Biol Med. 2000;130:769-71 pubmed..ApoC-III completely blocked oxidative phosphorylation during oxidation of palmitoyl carnitine by mitochondria, while the respiration rate in metabolic state 4 remained unchanged. ..
- Meyer B, Duvillard L, Owen A, Packard C, Caslake M. Fractionation of cholesteryl ester rich intermediate density lipoprotein subpopulations by chondroitin sulphate. Atherosclerosis. 2007;195:e28-34 pubmed..It remains to be determined if these cholesterol rich IDL particles are potentially more atherogenic than the triglyceride rich IDL particles. ..
- Tornero F, García Garzón A, Rincon B, Prieto S, Uson J, Lozano L. [Apolipoprotein C-II and C-III anomalies in normolipemic and hyperlipemic patients with chronic kidney failure]. Nefrologia. 2000;20:47-53 pubmed....
- Zeng Q, Dammerman M, Takada Y, Matsunaga A, Breslow J, Sasaki J. An apolipoprotein CIII marker associated with hypertriglyceridemia in Caucasians also confers increased risk in a west Japanese population. Hum Genet. 1995;95:371-5 pubmed..The results suggest that S2-M2 chromosomes carry HTG susceptibility sequences that predate the separation of the Asian and Caucasian races. ..