The APOA1/C3/A4/A5 gene cluster, lipid metabolism and cardiovascular disease risk

Current Opinion in Lipidology

Volumn 16, Issue 2, 2005, Pages 153-166

  Lai, Chao Qiang ^a   Parnell, Laurence D ^a   Ordovas, Jose M ^a  

^a TUFTS UNIVERSITY   (United States)

Author keywords

Apolipoprotein A1 C3 A4 A5; Cardiovascular disease risk; Haplotype; Linkage disequilibrium; Promoter; Regulatory

Indexed keywords

APOLIPOPROTEIN A1; APOLIPOPROTEIN A4; APOLIPOPROTEIN A5; APOLIPOPROTEIN C3; LIPID;

CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; ENVIRONMENTAL FACTOR; GENE CLUSTER; GENE EXPRESSION; GENE LINKAGE DISEQUILIBRIUM; GENETIC ASSOCIATION; GENETIC POLYMORPHISM; GENETIC VARIABILITY; GENOMICS; HAPLOTYPE; HUMAN; LIPID BLOOD LEVEL; LIPID METABOLISM; LIPOPROTEIN METABOLISM; NUCLEOTIDE SEQUENCE; PHENOTYPE; PRIORITY JOURNAL; PROMOTER REGION; REVIEW; TRANSCRIPTION REGULATION;

EID: 17144407255     PISSN: 09579672     EISSN: None     Source Type: Journal    
DOI: 10.1097/01.mol.0000162320.54795.68     Document Type: Review

References (117)

1. Karathanasis SK. Apolipoprotein multigene family: tandem organization of human apolipoprotein AI, CIII, and AIV genes. Proc Natl Acad Sci U S A 1985; 82:6374-6378.
2. Haddad IA, Ordovas JM, Fitzpatrick T, Karathanasis SK. Linkage, evolution, and expression of the rat apolipoprotein A-I, C-III, and A-IV genes. J Biol Chem 1986; 261:13268-13277.
3. Pennacchio LA, Olivier M, Hubacek JA, et al. An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing. Science 2001; 294:169-173.
4. van der Vliert HN, Sammels MG, Leegwater ACJ, et al. Apolipoprotein A-V - apolipoprotein A-V - a novel apolipoprotein associated with an early phase of liver regeneration. J Biol Chem 2001; 276:44512-44520.
5. Groenendijk M, Cantor RM, de Bruin TWA, et al. The apoAI-CIII-AIV gene cluster - review. Atherosclerosis 2001; 157:1-11.
6. van Dijk KW, Rensen PC, Voshol PJ, et al. The role and mode of action of apolipoproteins CIII and AV: synergistic actors in triglyceride metabolism? Curr Opin Lipidol 2004; 15:239-246. A recent and excellent review on the function and possible interaction between APOC3 and A5.
7. Pennacchio LA, Rubin EM. Apolipoprotein A5, a newly identified gene that affects plasma triglyceride levels in humans and mice. Arterioscler Thromb Vasc Biol 2003; 23:529-534.
8. Sorci-Thomas MG, Prack MM, Dashti N, et al. Differential effects of dietary fat on the tissue-specific expression of the apolipoprotein A-I gene: relationship to plasma concentration of high density lipoproteins. J Lipid Res 1989; 30:1397-1403.
9. Rubin EM, Krauss RM, Spangler EA, et al. Inhibition of early atherogenesis in transgenic mice by human apolipoprotein AI. Nature 1991; 353:265-267.
10. Herbert PN, Assmann G, Grotton JAM, Fredrickson DS. Disorders of lipid and lipoprotein metabolism. In: Stanbury JB, Wyngaarden DS, Fredrickson DS, et al., editors. Metabolic basis of inherited disease. New York: McGraw-Hill; 1999. pp. 589-651.
11. Lambert DA, Catapano AL, Smith LC, et al. Effect of the apolipoprotein C-II/C-III1 ratio on the capacity of purified milk lipoprotein lipase to hydrolyse triglycerides in monolayer vesicles. Atherosclerosis 1996; 127:205-212.
12. Ito Y, Azrolan N, O'Connell A, et al. Hypertriglyceridemia as a result of human apoCIII gene expression in transgenic mice. Science 1990; 249:790-793.
13. Ebara T, Ramakrishnan R, Steiner G, Shachter NS. Chylomicronemia due to apolipoprotein CIII overexpression in apolipoprotein E-null mice: apolipoprotein CIII-induced hypertriglyceridemia is not mediated by effects on apolipoprotein E. J Clin Invest 1997; 99:2672-2681.
14. Maeda N, Li H, Lee D, et al. Targeted disruption of the apolipoprotein C-III gene in mice results in hypotriglyceridemia and protection from postprandial hypertriglyceridemia. J Biol Chem 1994; 269:23610-23616.
15. Swaney J B, Braithwaite F, Eder HA. Characterization of the apolipoproteins of rat plasma lipoproteins. Biochemistry 1977; 16:271-278.
16. Beisiegel U, Utermann G. An apolipoprotein homolog of rat apolipoprotein A-IV in human plasma. Eur J Biochem 1979; 93:601-608.
17. Cohen RD, Castellani LW, Qiao JH, et al. Reduced aortic lesions and elevated high density lipoprotein levels in transgenic mice overexpressing mouse apolipoprotein A-IV. J Clin Invest 1997; 99:1906-1916.
18. Clark AG. The role of haplotypes in candidate gene studies. Genet Epidemiol 2004; 27:321-333.
19. Ordovas JM, Civeira F, Genest J Jr, et al. Restriction fragment length polymorphisms of the apolipoprotein A-I, C-III, A-IV gene locus. Relationships with lipids, apolipoproteins, and premature coronary artery disease. Atherosclerosis 1991; 87:75-86.
20. Pennacchio LA, Olivier M, Hubacek JA, et al. Two independent apolipoprotein A5 haplotypes influence human plasma triglyceride levels. Hum Mol Genet 2002; 11:3031-3038.
21. Lai CQ, Demissie S, Cupples LA, et al. Influence of the APOA5 locus on plasma triglyceride, lipoprotein subclasses, and CVD risk in the Framingham Heart Study. J Lipid Res 2004; 45:2096-2105.
22. Talmud PJ, Hawe E, Martin S, et al. Relative contribution of variation within the APOC3/A4/A5 gene cluster in determining plasma triglycerides. Hum Mol Genet 2002; 11:3039-3046.
23. Olivier M, Wang X, Cole R, et al. Haplotype analysis of the apolipoprotein gene cluster on human chromosome 11. Genomics 2004; 83:912-923. Extensive analyses of LD and haplotype structure within the A1/C3/A4/A5 cluster.
24. Stumpf MPH, Goldstein DB. Demography, recombination hotspot intensity, and the block structure of linkage disequilibrium. Curr Biol 2003; 13:1-8.
25. Fullerton SM, Buchanan AV, Sonpar VA, et al. The effects of scale: variation in the APOA1/C3/A4/A5 gene cluster. Hum Genet 2004; 115:36-56. An extensive investigation by resequencing on LD and haplotype structures within the A1/C3A4/A5 cluster among three populations.
26. Fu YX, Li WH. Statistical tests of neutrality of mutations. Genetics 1993; 133:693-709.
27. Fay JC, Wu CI. Hitchhiking under positive Darwinian selection. Genetics 2000; 155:1405-1413.
28. Stram DO, Haiman CA, Hirschhorn JN, et al. Choosing haplotype-tagging SNPs based on unphased genotype data using a preliminary sample of unrelated subjects with an example from the multiethnic cohort study. Hum Hered 2003; 55:27-36.
29. Stephens M, Smith NJ, Donnelly P. A new statistical method for haplotype reconstruction from population data. Am J Hum Genet 2001; 68:978-989.
30. Goldstein DB, Ahmadi KR, Weale ME, et al. Genome scans and candidate gene approaches in the study of common diseases and variable drug responses. Trends Genet 2003; 19:615-622.
31. Ding K, Zhou K, Zhang J, et al. The effect of haplotype block definitions on inference of haplotype block structure and htSNPs selection. Mol Biol Evol 2004; MBE Advance Access published 15 September 2004.
32. Lai CQ, Tai ES, Tan CE, et al. The APOA5 locus is a strong determinant of plasma triglyceride concentrations across ethnic groups in Singapore. J Lipid Res 2003; 44:2365-2373.
33. Li G-P, Wang J-Y, Yan S-K, et al. Genetic effect two polymorphisms in the apolipoprotein A5 gene and apolipoprotein C3 gene on serum lipids and lipoproteins levels in a Chinese population. Clin Genet 2004; 65:470-476.
34. Austin MA, Talmud PJ, Farin FM, et al. Association of apolipoprotein A5 variants with LDL particle size and triglyceride in Japanese Americans. Biochim Biophys Acta 2004; 1688:1-9.
35. Wang Q-F, Liu X, O'Connell J, et al. Haplotypes in the APOA1-C3-A4-A5 gene cluster affect plasma lipids in both humans and baboons. Hum Mol Genet 2004; 13:1049-1056. An investigation of LD and haplotype structures in humans and baboons.
36. Talianidis I, Tambakaki A, Toursounova J, Zannis VI. Complex interactions between SP1 bound to multiple distal regulatory sites and HNF4 bound to the proximal promoter lead to transcriptional activation of liver-specific human APOCIII gene. Biochemistry 1995; 34:10298-10309.
37. Ktistaki E, Lacorte JM, Katrakili N, et al. Transcriptional regulation of the apolipoprotein A-IV gene involves synergism between a proximal orphan receptor response element and a distant enhancer located in the upstream promoter region of the apolipoprotein C-III gene. Nucl Acids Res 1994; 22:4689-4696.
38. Kardassis D, Tzameli I, Hadzopoulou-Cladaras M, et al. Distal apolipoprotein C-III regulatory elements F to J act as a general modular enhancer for proximal promoters that contain hormone response elements. Synergism between hepatic nuclear factor-4 molecules bound to the proximal promoter and distal enhancer sites. Arterioscler Thromb Vasc Biol 1997; 17:222-232.
39. Pagani F, Sidoli A, Giudici GA, et al. Human apolipoprotein A-I gene promoter polymorphism: association with hyperalphalipoproteinemia. J Lipid Res 1990; 31:1371-1377.
40. Talmud PJ, Shu Y, Humphries SE. Polymorphism in the promoter region of the apolipoprotein A-I gene associated with differences in apolipoprotein A-I levels: the European Atherosclerosis Research study. Genet Epidemiol 1994; 11:265-280.
41. Saha N, Tay JSH, Low PS, Humphries SE. Guanidine to adenine (G/A) substitution in the promoter region of the apolipoprotein A-I gene is associated with elevated serum apolipoprotein A-I levels in Chinese non-smokers. Genet Epidemiol 1994; 11:255-264.
42. Peacock RE, Hamsten A, Johansson J, et al. Association of genotypes at the apolipoprotein AI-CIII-AIV, apolipoprotein B and lipoprotein lipase gene loci with coronary atherosclerosis and high density lipoprotein subclasses. Clin Genet 1994; 46:273-282.
43. Peacock RE, Temple A, Gudnason V, et al. Variation at the lipoprotein lipase and apolipoprotein AI-CIII gene loci are associated with fasting lipid and lipoprotein traits in a population sample from Iceland: interaction between genotype, gender, and smoking status. Genet Epidemiol 1997; 14:265-282.
44. Shioji K, Mannami T, Kokubo Y, et al. An association analysis between ApoA1 polymorphisms and the high-density lipoprotein (HDL) cholesterol level and myocardial infarction (MI) in Japanese. J Hum Genet 2004; 49:433-439.
45. Olivieri O, Stranieri C, Bassi A, et al. Apolipoprotein CIII gene polymorphisms and risk of coronary artery disease. J Lipid Res 43: 1450-1457.
46. Olivieri O, Bassi A, Stranieri C, et al. Apolipoprotein C-III, metabolic syndrome, and risk of coronary artery disease. J Lipid Res 2003; 44:2374-2381.
47. Li WW, Dammerman MM, Smith JD, et al. Common genetic variation in the promoter of the human apo CIII gene abolishes regulation by insulin and may contribute to hypertriglyceridemia. J Clin Invest 1995; 96:2601-2605.
48. von Eckardstein A, Funke H, Schulte M, et al. Nonsynonymous polymorphic sites in the apolipoprotein (apo) A-IV gene are associated with changes in the concentration of apo B- and apo A-I-containing lipoproteins in a normal population. Am J Hum Genet 1992; 50:1115-1128.
49. Saha N, Wang G, Vasisht S, Kamboh MI. Influence of two apo A4 polymorphisms at codons 347 and 360 on non-fasting plasma lipoprotein-lipids and apolipoproteins in Asian Indians. Atherosclerosis 1997; 131:249-255.
50. Seda O, Sedova L. New apolipoprotein A-V: comparative genomics meets metabolism. Physiol Res 2003; 52:141-146.
51. Eichenbaum-Voline S, Olivier M, Jones EL, et al. Linkage and association between distinct variants of the APOA1/C3/A4/A5 gene cluster and familial combined hyperlipidemia. Arterioscler Thromb Vasc Biol 2004; 24:167-174.
52. Mar R, Pajukanta P, Allayee H, et al. Association of the apolipoprotein A1/C3/A4/A5 gene cluster with triglyceride levels and LDL particle size in familial combined hyperlipidemia. Circ Res 2004; 94:993-999.
53. Talmud PJ, Martin S, Taskinen MR, et al. APOA5 gene variants, lipoprotein particle distribution, and progression of coronary heart disease: results from the LOCAT study. J Lipid Res 2004; 45:750-756.
54. Lee KW, Ayyobi AF, Frohlich JJ, Hill JS. APOA5 gene polymorphism modulates levels of triglyceride, HDL cholesterol and FERHDL but is not a risk factor for coronary artery disease. Atherosclerosis 2004; 176:165-172.
55. Szalai C, Keszei M, Duba J, et al. Polymorphism in the promoter region of the apolipoprotein A5 gene is associated with an increased susceptibility for coronary artery disease. Atherosclerosis 2004; 173:109-114.
56. Hubacek JA, Skodova Z, Adamkova V, et al. The influence of APOAV polymorphisms (T-1131 > C and S19 > W) on plasma triglyceride levels and risk of myocardial infarction. Clin Genet 2004; 65:126-130.
57. Bi N, Van S-K, Li G-P, et al. A single nucleotide polymorphism -1131T > C in the apolipoprotein A5 gene is associated with an increased risk of coronary artery disease and alters triglyceride metabolism in Chinese. Mol Genet Metab 2004; 83:280-286.
58. Liu HK, Wang CT, Zhang SZ, et al. Association of APOA5 gene single nucleotide polymorphism with levels of lipids and coronary heart disease in Chinese [in Chinese]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2004; 21:335-338.
59. Martin S, Nicaud V, Humphries SE, Talmud PJ, and the EARS group. Contribution of APOA5 gene variants to plasma triglyceride determination and to the response to both fat and glucose tolerance challenges. Biochim Biophys Acta 2003; 1637:217-225.
60. Liu S, Song YQ, Hu FB, et al. A prospective study of the APOA1 Xmnl and APOC3 Sstl polymorphisms in the APOA1/C3/A4 gene cluster and risk of incident myocardial infarction in men. Atherosclerosis 2004; 177:119-126.
61. Masana L, Ribalta J, Salazar J, et al. The apolipoprotein AV gene and diurnal triglyceridaemia in normolipidaemic subjects. Clin Chem Lab Med 2003; 41:517-521.
62. Ordovas JM, Corella D. Genes, diet and plasma lipids: the evidence from observational studies. World Rev Nutr Diet 2004; 93:41-76. A recent review of gene and diet interactions on plasma lipids.
63. Ordovas JM, Corella D. Nutritional genomics. Annu Rev Genom Hum Genet 2004; 5:71-118.
64. Ordovas JM. The quest for cardiovascular health in the genomic era: nutrigenetics and plasma lipoproteins. Proc Nutr Soc 2004; 63:145-152. A recent review of nutrition and genomics and cardiovascular health.
65. Karpe F. Postprandial lipoprotein metabolism and atherosclerosis. J Intern Med 1999; 246:341-355.
66. Jang Y, Kim JY, Kim OY, et al. The -1131T > C polymorphism in the apolipoprotein A5 gene is associated with postprandial hypertriacylglycerolemia; elevated small, dense LDL concentrations; and oxidative stress in nonobese Korean men. Am J Clin Nutr 2004; 80:832-840.
67. Altomonte J, Cong L, Harbaran S, et al. Foxol mediates insulin action on apoC-III and triglyceride metabolism. J Clin Invest 2004; 114:1493-1503. This study provides a clearer definition of the link between APOC3 (gene) and insulin-mediated gene expression.
68. Horikawa Y, Oda N, Cox NJ, et al. Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus. Nat Genet 2000; 26:163-175.
69. Gretarsdottir S, Thorleifsson G, Reynisdottir ST, et al. The gene encoding phosphodiesterase 4D confers risk of ischemic stroke. Nat Genet 2003; 35:131-138.
70. Pastinen T, Hudson TJ. Cis-acting regulatory variation in the human genome. Science 2004; 306:647-650.
71. Lira ME, Lloyd DB, Hallowell S, et al. Highly polymorphic repeat region in the CETP promoter induces unusual DNA structure. Biochim Biophys Acta 2004; 1684:38-45.
72. Dachet C, Poirier O, Cambien F, et al. New functional promoter polymorphism, CETP/-629, in cholesteryl ester transfer protein (CETP) gene related to CETP mass and high density lipoprotein cholesterol levels: role of Sp1/Sp3 in transcriptional regulation. Arterioscler Thromb Vasc Biol 2000; 20:507-515.
73. Le Goff W, Guerin M, Petit L, et al. Regulation of human CETP gene expression: role of SP1 and SP3 transcription factors at promoter sites -690, -629, and -37. J Lipid Res 2003; 44:1322-1331.
74. Wung SF, Aouizerat BE. Gender and ethnic differences in a case-control study of dyslipidemia: using the apolipoprotein A-V gene as an exemplar in cardiovascular genetics. Res Theory Nurs Pract 2003; 17:281-299; discussion 335-338.
75. Prieur X, Coste H, Rodriguez JC. The human apolipoprotein AV gene is regulated by peroxisome proliferator-activated receptor-alpha and contains a novel farnesoid X-activated receptor response element. J Biol Chem 2003; 278:25468-25480.
76. Vu-Dac N, Gervois P, Jakel H, et al. Apolipoprotein A5, a crucial determinant of plasma triglyceride levels, is highly responsive to peroxisome proliferator-activated receptor α activators. J Biol Chem 2003; 278:17982-17985.
77. Jakel H, Nowak M, Moitrot E, et al. The liver X receptor ligand T0901317 down-regulates APOA5 gene expression through activation of SREBP-1c. J Biol Chem 2004; 279:45462-45469.
78. Sauvaget D, Chauffeton V, Citadelle D, et al. Restriction of apolipoprotein A-IV gene expression to the intestine villus depends on a hormone-responsive element and parallels differential expression of the hepatic nuclear factor 4α and γ isoforms. J Biol Chem 2002; 277:34540-34548.
79. Minihane AM, Finnegan YE, Talmud P, et al. Influence of the APOC3 -2854T > G polymorphism on plasma lipid levels: effect of age and gender. Biochim Biophys Acta 2002; 1583:311-314.
80. Ogami K, Hadzopoulou-Cladaras M, Cladaras C, Zannis VI. Promoter elements and factors required for hepatic and intestinal transcription of the human ApoCIII gene. J Biol Chem 1990; 265:9808-9815.
81. Lavrentiadou SN, Hadzopoulou-Cladaras M, Kardassis D, Zannis VI. Binding specificity and modulation of the human ApoCIII promoter activity by heterodimers of ligand-dependent nuclear receptors. Biochemistry 1999; 38:964-975.
82. Brown S, Ordovas JM, Campos H. Interaction between the APOC3 gene promoter polymorphisms, saturated fat intake and plasma lipoproteins. Atherosclerosis 2003; 170:307-313.
83. Waterworth DM, Talmud PJ, Luan J, et al. Variants in the APOC3 promoter insulin responsive element modulate insulin secretion and lipids in middle-aged men. Biochim Biophys Acta 2003; 1637:200-206.
84. Sass C, Cheng S, Siest G, Visvikis S. Genetic influences on blood pressure within the Stanislas Cohort. J Hypertens 2004; 22:297-304.
85. Cladaras C, Ogami K, Kardassis D, et al. Recognition of proximal human apoCIII promoter by NFY* type, C/EBP and a family of heat stable activities [Abstract]. Circulation 1991; 84(Suppl. II):II-109.
86. Pastier D, Lacorte JM, Chambaz J, et al. Two initiator-like elements are required for the combined activation of the human apolipoprotein C-III promoter by upstream stimulatory factor and hepatic nuclear factor-4. J Biol Chem 2002; 277:15199-15206.
87. Coste H, Rodriguez JC. Orphan nuclear receptor Rev-erbα regulates the human apolipoprotein CIII promoter. J Biol Chem 2002; 277:27120-27129.
88. Murao K, Wada Y, Nakamura T, et al. Effects of glucose and insulin on rat apolipoprotein A-I gene expression. J Biol Chem 1998; 273:18959-18965.
89. Rottman JN, Widom RL, Nadal-Ginard B, et al. A retinoic acid-responsive element in the apolipoprotein AI gene distinguishes between two different retinoic acid response pathways. Mol Cell Biol 1991; 11:3814-3820.
90. Haas MJ, Horani M, Mreyoud A, et al. Suppression of apolipoprotein AI gene expression in HepG2 cells by TNF alpha and IL-1 beta. Biochim Biophys Acta 2003; 1623:120-128.
91. Widom RL, Ladias JA, Kouidou S, Karathanasis SK. Synergistic interactions between transcription factors control expression of the apolipoprotein AI gene in liver cells. Mol Cell Biol 1991; 11:677-687.
92. Mietus-Snyder M, Sladek FM, Ginsburg GS, et al. Antagonism between apolipoprotein AI regulatory protein 1, Ear3/COUP-TF, and hepatocyte nuclear factor 4 modulates apolipoprotein CIII gene expression in liver and intestinal cells. Mol Cell Biol 1992; 12:1708-1718.
93. Zhang X, Chen Z-Q, Wang Z, et al. Protein-DNA interactions at a drug-responsive element of the human apolipoprotein A-I gene. J Biol Chem 1996; 271:27152-27160.
94. Garasto S, Rose G, Derango F, et al. The study of APOA1, APOC3 and APOA4 variability in healthy ageing people reveals another paradox in the oldest old subjects. Ann Hum Genet 2003; 67:54-62.
95. Vu-Dac N, Schoonjans K, Laine B, et al. Negative regulation of the human apolipoprotein A-I promoter by fibrates can be attenuated by the interaction of the peroxisome proliferator-activated receptor with its response element. J Biol Chem 1994; 269:31012-31018.
96. Haas MJ, Reinacher D, Li JP, et al. Regulation of apoA1 gene expression with acidosis: requirement for a transcriptional repressor. J Mol Endocrinol 2001; 27:43-57.
97. Angotti E, Mele E, Costanzo F, Avvedimento EV. A polymorphism (G > A transition) in the -78 position of the apolipoprotein A-I promoter in creases transcription efficiency. J Biol Chem 1994; 269:17371-17374.
98. Matsunaga A, Sasaki J, Han H, et al. Compound heterozygosity for an apolipoprotein A1 gene promoter mutation and a structural nonsense mutation with apolipoprotein A1 deficiency. Arterioscler Thromb Vasc Biol 1999; 19:348-355.
99. Ordovas JM, Corella D, Cupples LA, et al. Polyunsaturated fatty acids modulate the effects of the APOA1 G-A polymorphism on HDL-cholesterol concentrations in a sex-specific manner: the Framingham Study. Am J Clin Nutr 2002; 75:38-46.
100. Jump DB. Dietary polyunsaturated fatty acids and regulation of gene transcription. Curr Opin Lipidol 2002; 13:155-164.
101. Naganawa S, Ginsberg HN, Glickman RM, Ginsburg GS. Intestinal transcription and synthesis of apolipoprotein AI is regulated by five natural polymorphisms upstream of the apolipoprotein CIII gene. J Clin Invest 1997; 8:1958-1965.
102. Harnish DC, Evans MJ, Scicchitano MS, et al. Estrogen regulation of the apolipoprotein AI gene promoter through transcription cofactor sharing. J Biol Chem 1998; 273:9270-9278.
103. Waterland RA, Jirtle RL. Early nutrition, epigenetic changes at transposons and imprinted genes, and enhanced susceptibility to adult chronic diseases. Nutrition 2004; 20:63-68.
104. Putt W, Palmen J, Nicaud V, et al. Variation in USF1 shows haplotype effects, gene:gene and gene:environment associations with glucose and lipid parameters in the European Atherosclerosis Research Study II. Hum Mol Genet 2004; 13:1587-1597.
105. Pajukanta P, Lilja HE, Sinsheimer JS, et al. Familial combined hyperlipidemia is associated with upstream transcription factor 1 (USF1). Nat Genet 2004; 36:371-376. Brings to light the role of USF transcription factors in FCHL via an integration of polymorphism analysis, transcription regulation and comparative genomics.
106. Bisaha JG, Simon TC, Gordon JI, Breslow JL. Characterization of an enhancer element in the human apolipoprotein C-III gene that regulates human apolipoprotein A-I gene expression in the intestinal epithelium. J Biol Chem 1995; 270:19979-19988.
107. Kellis M, Patterson N, Endrizzi M, et al. Sequencing and comparison of yeast species to identify genes and regulatory elements. Nature 2003; 423:241-254.
108. Cliften P, Sudarsanam P, Desikan A, et al. Finding functional features in Saccharomyces genomes by phylogenetic footprinting. Science 2003; 301:71-76.
109. Wang T, Stormo GD. Combining phylogenetic data with co-regulated genes to identify regulatory motifs. Bioinformatics 2003; 19:2369-2380.
110. Pritsker M, Liu YC, Beer MA, Tavazoie S. Whole-genome discovery of transcription factor binding sites by network-level conservation. Genome Res 2004; 14:99-108.
111. Harbison CT, Gordon DB, Lee TI, et al. Transcriptional regulatory code of a eukaryotic genome. Nature 2004; 431:99-104.
112. Miller W, Makova KD, Nekrutenko A, Hardison RC. Comparative genomics. Annu Rev Genom 2004; 5:15-56. A noteworthy review indicating the value of a comparative genomics approach to the identification of important genome features.
113. Buckland PR, Hoogendoorn B, Guy CA, et al. A high proportion of polymorphisms in the promoters of brain expressed genes influences transcriptional activity. Biochim Biophys Acta 2004; 1690:238-249. An exciting finding that promoter polymorphisms are rich in functionality.
114. ENCODE Project Consortium. The ENCODE (ENCyclopedia Of DNA Elements) project. Science 2004; 306:636-640.
115. Nobrega MA, Pennacchio LA. Comparative genomic analysis as a tool for biological discovery. J Physiol 2004; 554:31-39.
116. Schwartz S, Zhang Z, Frazer KA, et al. PipMaker - a web server for aligning two genomic DNA sequences. Genome Res 2000; 10:577-586.
117. Elshourbagy NA, Walker DW, Paik Y-K, et al. Structure and expression of the human apolipoprotein A-IV gene. J Biol Chem 1987; 262:7973-7981.