Disparities in allele frequencies and population differentiation for 101 disease-associated single nucleotide polymorphisms between Puerto Ricans and non-Hispanic whites

Josiemer Mattei, Laurence D Parnell, Chao-Qiang Lai, Bibiana Garcia-Bailo, Xian Adiconis, Jian Shen, Donna Arnett, Serkalem Demissie, Katherine L Tucker, Jose M Ordovas, Josiemer Mattei, Laurence D Parnell, Chao-Qiang Lai, Bibiana Garcia-Bailo, Xian Adiconis, Jian Shen, Donna Arnett, Serkalem Demissie, Katherine L Tucker, Jose M Ordovas

Abstract

Background: Variations in gene allele frequencies can contribute to differences in the prevalence of some common complex diseases among populations. Natural selection modulates the balance in allele frequencies across populations. Population differentiation (FST) can evidence environmental selection pressures. Such genetic information is limited in Puerto Ricans, the second largest Hispanic ethnic group in the US, and a group with high prevalence of chronic disease. We determined allele frequencies and population differentiation for 101 single nucleotide polymorphisms (SNPs) in 30 genes involved in major metabolic and disease-relevant pathways in Puerto Ricans (n = 969, ages 45-75 years) and compared them to similarly aged non-Hispanic whites (NHW) (n = 597).

Results: Minor allele frequency (MAF) distributions for 45.5% of the SNPs assessed in Puerto Ricans were significantly different from those of NHW. Puerto Ricans carried risk alleles in higher frequency and protective alleles in lower frequency than NHW. Patterns of population differentiation showed that Puerto Ricans had SNPs with exceptional FST values in intronic, non-synonymous and promoter regions. NHW had exceptional FST values in intronic and promoter region SNPs only.

Conclusion: These observations may serve to explain and broaden studies on the impact of gene polymorphisms on chronic diseases affecting Puerto Ricans.

Figures

Figure 1
Figure 1
Differences in protective (upper panel) or risk (lower panel) minor allele frequency in Puerto Rican versus non-Hispanic whites, by SNP. Tables describe the associated phenotypes for those SNPs with significantly different MAF between populations. *Significantly different MAF between populations, p < 0.0005 Abbreviations: MAF: minor allele frequency; HDL-C: high density lipoprotein; T2DM: type 2 diabetes mellitus; HOMA-IR: homeostasis model assessment of insulin resistance; CAD: coronary artery disease; BMI: body mass index; TG: triglycerides; LDL-C: low density lipoprotein; VLDL-C: very low density lipoprotein; TC: total cholesterol; IHD: ischemic heart disease; CHD: coronary heart disease; HbA1c: glycosylated hemoglobin.
Figure 2
Figure 2
FST range (filled circle) for Puerto Ricans (a) and non-Hispanic whites (b) by SNP function. Open squares represent mean FST and bars represent three standard deviations from the mean for each SNP function.

References

    1. United States Census Bureau: United States General Demographic Characteristics: 2004 American Community Survey
    1. Zsembik BA, Fennell D. Ethnic variation in health and the determinants of health among Latinos. Soc Sci Med. 2005;61:53–63. doi: 10.1016/j.socscimed.2004.11.040.
    1. Hajat A, Lucas JB, Kington R. Health outcomes among Hispanic subgroups: data from the National Health Interview Survey, 1992–95. Adv Data. 2000:1–14.
    1. Cleghorn GD, Nguyen M, Roberts B, Duran G, Tellez T, Alecon M. Practice-based interventions to improve health care for Latinos with diabetes. Ethn Dis. 2004;14:S117–121.
    1. Lin H, Bermudez OI, Falcon LM, Tucker KL. Hypertension among Hispanic elders of a Caribbean origin in Massachusetts. Ethn Dis. 2002;12:499–507.
    1. Falcon LM, Tucker KL. Prevalence and correlates of depressive symptoms among Hispanic elders in Massachusetts. J Gerontol B Psychol Sci Soc Sci. 2000;55:S108–116.
    1. Denney JT, Krueger PM, Rogers RG, Boardman JD. Race/ethnic and sex differentials in body mass among US adults. Ethn Dis. 2004;14:389–398.
    1. Bermudez OI, Tucker KL. Total and central obesity among elderly Hispanics and the association with Type 2 diabetes. Obes Res. 2001;9:443–451. doi: 10.1038/oby.2001.58.
    1. Tucker KL, Falcon LM, Bianchi LA, Cacho E, Bermudez OI. Self-reported prevalence and health correlates of functional limitation among Massachusetts elderly Puerto Ricans, Dominicans, and non-Hispanic white neighborhood comparison group. J Gerontol A Biol Sci Med Sci. 2000;55:M90–97.
    1. American Diabetes Association Total Prevalence of Diabetes &Pre-diabetes
    1. Oquendo MA, Lizardi D, Greenwald S, Weissman MM, Mann JJ. Rates of lifetime suicide attempt and rates of lifetime major depression in different ethnic groups in the United States. Acta Psychiatr Scand. 2004;110:446–451. doi: 10.1111/j.1600-0447.2004.00404.x.
    1. Martinez-Cruzado JC, Toro-Labrador G, Viera-Vera J, Rivera-Vega MY, Startek J, Latorre-Esteves M, Roman-Colon A, Rivera-Torres R, Navarro-Millan IY, Gomez-Sanchez E, et al. Reconstructing the population history of Puerto Rico by means of mtDNA phylogeographic analysis. Am J Phys Anthropol. 2005;128:131–155. doi: 10.1002/ajpa.20108.
    1. Gonzalez Burchard E, Borrell LN, Choudhry S, Naqvi M, Tsai HJ, Rodriguez-Santana JR, Chapela R, Rogers SD, Mei R, Rodriguez-Cintron W, et al. Latino populations: a unique opportunity for the study of race, genetics, and social environment in epidemiological research. Am J Public Health. 2005;95:2161–2168. doi: 10.2105/AJPH.2005.068668.
    1. Choudhry S, Coyle NE, Tang H, Salari K, Lind D, Clark SL, Tsai HJ, Naqvi M, Phong A, Ung N, et al. Population stratification confounds genetic association studies among Latinos. Hum Genet. 2006;118:652–664. doi: 10.1007/s00439-005-0071-3.
    1. Taioli E, Pedotti P, Garte S. Importance of allele frequency estimates in epidemiological studies. Mutat Res. 2004;567:63–70. doi: 10.1016/j.mrrev.2004.06.001.
    1. Race, Ethnicity, Genetics Working Group The use of racial, ethnic, and ancestral categories in human genetics research. Am J Hum Genet. 2005;77:519–532. doi: 10.1086/491747.
    1. Goddard KA, Hopkins PJ, Hall JM, Witte JS. Linkage disequilibrium and allele-frequency distributions for 114 single-nucleotide polymorphisms in five populations. Am J Hum Genet. 2000;66:216–234. doi: 10.1086/302727.
    1. Ioannidis JP, Ntzani EE, Trikalinos TA. 'Racial' differences in genetic effects for complex diseases. Nat Genet. 2004;36:1312–1318. doi: 10.1038/ng1474.
    1. Spielman RS, Bastone LA, Burdick JT, Morley M, Ewens WJ, Cheung VG. Common genetic variants account for differences in gene expression among ethnic groups. Nat Genet. 2007;39:226–231. doi: 10.1038/ng1955.
    1. Lan Q, Shen M, Garcia-Rossi D, Chanock S, Zheng T, Berndt SI, Puri V, Li G, He X, Welch R, et al. Genotype frequency and F ST analysis of polymorphisms in immunoregulatory genes in Chinese and Caucasian populations. Immunogenetics. 2007;59:839–852. doi: 10.1007/s00251-007-0253-3.
    1. Lanfear DE, Marsh S, Cresci S, Shannon WD, Spertus JA, McLeod HL. Genotypes associated with myocardial infarction risk are more common in African Americans than in European Americans. J Am Coll Cardiol. 2004;44:165–167. doi: 10.1016/j.jacc.2004.03.053.
    1. Chandalia M, Grundy SM, Adams-Huet B, Abate N. Ethnic differences in the frequency of ENPP1/PC1 121Q genetic variant in the Dallas Heart Study cohort. J Diabetes Complications. 2007;21:143–148. doi: 10.1016/j.jdiacomp.2006.11.003.
    1. Pemberton TJ, Mehta NU, Witonsky D, Di Rienzo A, Allayee H, Conti DV, Patel PI. Prevalence of common disease-associated variants in Asian Indians. BMC Genet. 2008;9:13. doi: 10.1186/1471-2156-9-13.
    1. Myles S, Davison D, Barrett J, Stoneking M, Timpson N. Worldwide population differentiation at disease-associated SNPs. BMC Med Genomics. 2008;1:22. doi: 10.1186/1755-8794-1-22.
    1. Tang H, Choudhry S, Mei R, Morgan M, Rodriguez-Cintron W, Burchard EG, Risch NJ. Recent genetic selection in the ancestral admixture of Puerto Ricans. Am J Hum Genet. 2007;81:626–633. doi: 10.1086/520769.
    1. Kullo IJ, Ding K. Patterns of population differentiation of candidate genes for cardiovascular disease. BMC Genet. 2007;8:48. doi: 10.1186/1471-2156-8-48.
    1. Olshen AB, Gold B, Lohmueller KE, Struewing JP, Satagopan J, Stefanov SA, Eskin E, Kirchhoff T, Lautenberger JA, Klein RJ, et al. Analysis of genetic variation in Ashkenazi Jews by high density SNP genotyping. BMC Genet. 2008;9:14. doi: 10.1186/1471-2156-9-14.
    1. Rockman MV, Hahn MW, Soranzo N, Zimprich F, Goldstein DB, Wray GA. Ancient and recent positive selection transformed opioid cis-regulation in humans. PLoS Biol. 2005;3:e387. doi: 10.1371/journal.pbio.0030387.
    1. Barreiro LB, Laval G, Quach H, Patin E, Quintana-Murci L. Natural selection has driven population differentiation in modern humans. Nat Genet. 2008;40:340–345. doi: 10.1038/ng.78.
    1. Weir BS, Cardon LR, Anderson AD, Nielsen DM, Hill WG. Measures of human population structure show heterogeneity among genomic regions. Genome Res. 2005;15:1468–1476. doi: 10.1101/gr.4398405.
    1. Lai CQ, Tucker KL, Choudhry S, Parnell LD, Mattei J, Garcia-Bailo B, Beckman K, Burchard EG, Ordovas JM. Population admixture associated with disease prevalence in the Boston Puerto Rican health study. Hum Genet. 2009;125:199–209. doi: 10.1007/s00439-008-0612-7.
    1. Tucker KL. Stress and nutrition in relation to excess development of chronic disease in Puerto Rican adults living in the Northeastern USA. J Med Invest. 2005;52:252–258. doi: 10.2152/jmi.52.252.
    1. Lai CQ, Arnett DK, Corella D, Straka RJ, Tsai MY, Peacock JM, Adiconis X, Parnell LD, Hixson JE, Province MA, et al. Fenofibrate effect on triglyceride and postprandial response of apolipoprotein A5 variants: the GOLDN study. Arterioscler Thromb Vasc Biol. 2007;27:1417–1425. doi: 10.1161/ATVBAHA.107.140103.
    1. Lai CQ, Tucker KL, Parnell LD, Adiconis X, Garcia-Bailo B, Griffith J, Meydani M, Ordovas JM. PPARGC1A variation associated with DNA damage, diabetes, and cardiovascular diseases: the Boston Puerto Rican Health Study. Diabetes. 2008;57:809–816. doi: 10.2337/db07-1238.
    1. National Center for Biotechnology Information
    1. Livak KJ. Allelic discrimination using fluorogenic probes and the 5' nuclease assay. Genet Anal. 1999;14:143–149.
    1. Liu K, Muse SV. PowerMarker: an integrated analysis environment for genetic marker analysis. Bioinformatics. 2005;21:2128–2129. doi: 10.1093/bioinformatics/bti282.
    1. Weir BS, Hill WG. Estimating F-statistics. Annu Rev Genet. 2002;36:721–750. doi: 10.1146/annurev.genet.36.050802.093940.
    1. Akey JM, Zhang G, Zhang K, Jin L, Shriver MD. Interrogating a high-density SNP map for signatures of natural selection. Genome Res. 2002;12:1805–1814. doi: 10.1101/gr.631202.
    1. Bamshad M, Wooding S, Salisbury BA, Stephens JC. Deconstructing the relationship between genetics and race. Nat Rev Genet. 2004;5:598–609. doi: 10.1038/nrg1401.
    1. Burchard EG, Ziv E, Coyle N, Gomez SL, Tang H, Karter AJ, Mountain JL, Perez-Stable EJ, Sheppard D, Risch N. The importance of race and ethnic background in biomedical research and clinical practice. N Engl J Med. 2003;348:1170–1175. doi: 10.1056/NEJMsb025007.
    1. Lohmueller KE, Mauney MM, Reich D, Braverman JM. Variants associated with common disease are not unusually differentiated in frequency across populations. Am J Hum Genet. 2006;78:130–136. doi: 10.1086/499287.
    1. Payami H, Zhu M, Montimurro J, Keefe R, McCulloch CC, Moses L. One step closer to fixing association studies: evidence for age- and gender-specific allele frequency variations and deviations from Hardy-Weinberg expectations in controls. Hum Genet. 2005;118:322–330. doi: 10.1007/s00439-005-0057-1.
    1. Ylonen SK, Salminen I, Lyssenko V, Virtanen SM, Groop L, Aro A, Saloranta C. The Pro12Ala polymorphism of the PPAR-gamma2 gene affects associations of fish intake and marine n-3 fatty acids with glucose metabolism. Eur J Clin Nutr. 2008;62:1432–1439. doi: 10.1038/sj.ejcn.1602882.
    1. Rouse I. The Tainos: Rise and Decline of the People who Greeted Columbus. New Haven: Yale University Press; 1992.
    1. Lin H, Bermudez OI, Tucker KL. Dietary patterns of Hispanic elders are associated with acculturation and obesity. J Nutr. 2003;133:3651–3657.
    1. Tucker KL, Bianchi LA, Maras J, Bermudez OI. Adaptation of a food frequency questionnaire to assess diets of Puerto Rican and non-Hispanic adults. Am J Epidemiol. 1998;148:507–518.
    1. Tucker KL, Bermudez OI, Castaneda C. Type 2 diabetes is prevalent and poorly controlled among Hispanic elders of Caribbean origin. Am J Public Health. 2000;90:1288–1293. doi: 10.2105/AJPH.90.8.1288.
    1. Belle DJ, Singh H. Genetic factors in drug metabolism. Am Fam Physician. 2008;77:1553–1560.
    1. Buzzetti R, Petrone A, Ribaudo MC, Alemanno I, Zavarella S, Mein CA, Maiani F, Tiberti C, Baroni MG, Vecci E, et al. The common PPAR-gamma2 Pro12Ala variant is associated with greater insulin sensitivity. Eur J Hum Genet. 2004;12:1050–1054. doi: 10.1038/sj.ejhg.5201283.
    1. Deeb SS, Fajas L, Nemoto M, Pihlajamaki J, Mykkanen L, Kuusisto J, Laakso M, Fujimoto W, Auwerx J. A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nat Genet. 1998;20:284–287. doi: 10.1038/3099.
    1. Frederiksen L, Brodbaek K, Fenger M, Jorgensen T, Borch-Johnsen K, Madsbad S, Urhammer SA. Comment: studies of the Pro12Ala polymorphism of the PPAR-gamma gene in the Danish MONICA cohort: homozygosity of the Ala allele confers a decreased risk of the insulin resistance syndrome. J Clin Endocrinol Metab. 2002;87:3989–3992. doi: 10.1210/jc.87.8.3989.
    1. Altshuler D, Hirschhorn JN, Klannemark M, Lindgren CM, Vohl MC, Nemesh J, Lane CR, Schaffner SF, Bolk S, Brewer C, et al. The common PPARgamma Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes. Nat Genet. 2000;26:76–80. doi: 10.1038/79216.
    1. Ludovico O, Pellegrini F, Di Paola R, Minenna A, Mastroianno S, Cardellini M, Marini MA, Andreozzi F, Vaccaro O, Sesti G, et al. Heterogeneous effect of peroxisome proliferator-activated receptor gamma2 Ala12 variant on type 2 diabetes risk. Obesity (Silver Spring) 2007;15:1076–1081. doi: 10.1038/oby.2007.617.
    1. Lohmueller KE, Pearce CL, Pike M, Lander ES, Hirschhorn JN. Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease. Nat Genet. 2003;33:177–182. doi: 10.1038/ng1071.
    1. Temelkova-Kurktschiev T, Hanefeld M, Chinetti G, Zawadzki C, Haulon S, Kubaszek A, Koehler C, Leonhardt W, Staels B, Laakso M. Ala12Ala genotype of the peroxisome proliferator-activated receptor gamma2 protects against atherosclerosis. J Clin Endocrinol Metab. 2004;89:4238–4242. doi: 10.1210/jc.2003-032120.
    1. Sparso T, Andersen G, Nielsen T, Burgdorf KS, Gjesing AP, Nielsen AL, Albrechtsen A, Rasmussen SS, Jorgensen T, Borch-Johnsen K, et al. The GCKR rs780094 polymorphism is associated with elevated fasting serum triacylglycerol, reduced fasting and OGTT-related insulinaemia, and reduced risk of type 2 diabetes. Diabetologia. 2008;51:70–75. doi: 10.1007/s00125-007-0865-z.
    1. Xiao J, Zhang F, Wiltshire S, Hung J, Jennens M, Beilby JP, Thompson PL, McQuillan BM, McCaskie PA, Carter KW, et al. The apolipoprotein AII rs5082 variant is associated with reduced risk of coronary artery disease in an Australian male population. Atherosclerosis. 2008;199:333–339. doi: 10.1016/j.atherosclerosis.2007.11.017.
    1. Delgado-Lista J, Perez-Jimenez F, Tanaka T, Perez-Martinez P, Jimenez-Gomez Y, Marin C, Ruano J, Parnell L, Ordovas JM, Lopez-Miranda J. An apolipoprotein A-II polymorphism (-265T/C, rs5082) regulates postprandial response to a saturated fat overload in healthy men. J Nutr. 2007;137:2024–2028.
    1. Roberts CG, Shen H, Mitchell BD, Damcott CM, Shuldiner AR, Rodriguez A. Variants in scavenger receptor class B type I gene are associated with HDL cholesterol levels in younger women. Hum Hered. 2007;64:107–113. doi: 10.1159/000101962.
    1. Qi L, Corella D, Sorli JV, Portoles O, Shen H, Coltell O, Godoy D, Greenberg AS, Ordovas JM. Genetic variation at the perilipin (PLIN) locus is associated with obesity-related phenotypes in White women. Clin Genet. 2004;66:299–310. doi: 10.1111/j.1399-0004.2004.00309.x.
    1. Chien KL, Fang WH, Wen HC, Lin HP, Lin YL, Lin SW, Wu JH, Kao JT. APOA1/C3/A5 haplotype and risk of hypertriglyceridemia in Taiwanese. Clin Chim Acta. 2008;390:56–62. doi: 10.1016/j.cca.2007.12.014.
    1. Maasz A, Kisfali P, Horvatovich K, Mohas M, Marko L, Csongei V, Farago B, Jaromi L, Magyari L, Safrany E, et al. Apolipoprotein A5 T-1131C variant confers risk for metabolic syndrome. Pathol Oncol Res. 2007;13:243–247. doi: 10.1007/BF02893505.
    1. Szalai C, Keszei M, Duba J, Prohaszka Z, Kozma GT, Csaszar A, Balogh S, Almassy Z, Fust G, Czinner A. 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. doi: 10.1016/j.atherosclerosis.2003.12.003.
    1. Wang J, Ban MR, Kennedy BA, Anand S, Yusuf S, Huff MW, Pollex RL, Hegele RA. APOA5 genetic variants are markers for classic hyperlipoproteinemia phenotypes and hypertriglyceridemia. Nat Clin Pract Cardiovasc Med. 2008;5:730–737. doi: 10.1038/ncpcardio1326.
    1. Henneman P, Schaap FG, Havekes LM, Rensen PC, Frants RR, van Tol A, Hattori H, Smelt AH, van Dijk KW. Plasma apoAV levels are markedly elevated in severe hypertriglyceridemia and positively correlated with the APOA5 S19W polymorphism. Atherosclerosis. 2007;193:129–134. doi: 10.1016/j.atherosclerosis.2006.05.030.
    1. Samuels ME, Forbey KC, Reid JE, Abkevich V, Bulka K, Wardell BR, Bowen BR, Hopkins PN, Hunt SC, Ballinger DG, et al. Identification of a common variant in the lipoprotein lipase gene in a large Utah kindred ascertained for coronary heart disease: the -93G/D9N variant predisposes to low HDL-C/high triglycerides. Clin Genet. 2001;59:88–98. doi: 10.1034/j.1399-0004.2001.590205.x.
    1. Hoffer MJ, Bredie SJ, Snieder H, Reymer PW, Demacker PN, Havekes LM, Boomsma DI, Stalenhoef AF, Frants RR, Kastelein JJ. Gender-related association between the -93T-->G/D9N haplotype of the lipoprotein lipase gene and elevated lipid levels in familial combined hyperlipidemia. Atherosclerosis. 1998;138:91–99. doi: 10.1016/S0021-9150(98)00007-0.
    1. Kastelein JJ, Groenemeyer BE, Hallman DM, Henderson H, Reymer PW, Gagne SE, Jansen H, Seidell JC, Kromhout D, Jukema JW, et al. The Asn9 variant of lipoprotein lipase is associated with the -93G promoter mutation and an increased risk of coronary artery disease. The Regress Study Group. Clin Genet. 1998;53:27–33. doi: 10.1034/j.1399-0004.1998.531530106.x.
    1. Wittrup HH, Andersen RV, Tybjaerg-Hansen A, Jensen GB, Nordestgaard BG. Combined analysis of six lipoprotein lipase genetic variants on triglycerides, high-density lipoprotein, and ischemic heart disease: cross-sectional, prospective, and case-control studies from the Copenhagen City Heart Study. J Clin Endocrinol Metab. 2006;91:1438–1445. doi: 10.1210/jc.2005-1725.
    1. Garenc C, Couillard C, Laflamme N, Cadelis F, Gagne C, Couture P, Julien P, Bergeron J. Effect of the APOC3 Sst I SNP on fasting triglyceride levels in men heterozygous for the LPL P207L deficiency. Eur J Hum Genet. 2005;13:1159–1165. doi: 10.1038/sj.ejhg.5201469.
    1. Liu HK, Li XF, Zhang SZ, Ren Y, Yong X, Liu YQ, Wang CT, Chen X, Hu YM, Zhang L. Association of Sst I polymorphism in apolipoprotein C3 gene with hypertriglyceridaemia in coronary atherosclerotic heart disease and type II diabetes mellitus in Chinese population. Yi Chuan Xue Bao. 2005;32:11–18.
    1. Russo GT, Meigs JB, Cupples LA, Demissie S, Otvos JD, Wilson PW, Lahoz C, Cucinotta D, Couture P, Mallory T, et al. Association of the Sst-I polymorphism at the APOC3 gene locus with variations in lipid levels, lipoprotein subclass profiles and coronary heart disease risk: the Framingham offspring study. Atherosclerosis. 2001;158:173–181. doi: 10.1016/S0021-9150(01)00409-9.
    1. Chhabra S, Narang R, Krishnan LR, Vasisht S, Agarwal DP, Srivastava LM, Manchanda SC, Das N. Apolipoprotein C3 SstI polymorphism and triglyceride levels in Asian Indians. BMC Genet. 2002;3:9. doi: 10.1186/1471-2156-3-9.
    1. Han T, Jiang Z, Suo G, Zhang S. Apolipoprotein B-100 gene Xba I polymorphism and cholesterol gallstone disease. Clin Genet. 2000;57:304–308. doi: 10.1034/j.1399-0004.2000.570410.x.
    1. Li S, Lei ZW, Chen Z, Lin D, Ke XS, Zhong YM, Wu SF. [Relationship between apolipoprotein E and apolipoprotein B polymorphisms in youths with coronary heart disease] Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2003;20:241–243.
    1. Bernard S, Charriere S, Charcosset M, Berthezene F, Moulin P, Sassolas A. Relation between XbA1 apolipoprotein B gene polymorphism and cardiovascular risk in a type 2 diabetic cohort. Atherosclerosis. 2004;175:177–181. doi: 10.1016/j.atherosclerosis.2004.03.017.
    1. Hegele RA, Connelly PW, Hanley AJ, Sun F, Harris SB, Zinman B. Common genomic variation in the APOC3 promoter associated with variation in plasma lipoproteins. Arterioscler Thromb Vasc Biol. 1997;17:2753–2758.
    1. Martinelli N, Trabetti E, Bassi A, Girelli D, Friso S, Pizzolo F, Sandri M, Malerba G, Pignatti PF, Corrocher R, et al. The -1131 T>C and S19W APOA5 gene polymorphisms are associated with high levels of triglycerides and apolipoprotein C-III, but not with coronary artery disease: an angiographic study. Atherosclerosis. 2007;191:409–417. doi: 10.1016/j.atherosclerosis.2006.04.009.
    1. Talmud PJ, Hawe E, Martin S, Olivier M, Miller GJ, Rubin EM, Pennacchio LA, Humphries SE. Relative contribution of variation within the APOC3/A4/A5 gene cluster in determining plasma triglycerides. Hum Mol Genet. 2002;11:3039–3046. doi: 10.1093/hmg/11.24.3039.
    1. Muendlein A, Saely CH, Marte T, Schmid F, Koch L, Rein P, Langer P, Aczel S, Drexel H. Synergistic effects of the apolipoprotein E epsilon3/epsilon2/epsilon4, the cholesteryl ester transfer protein TaqIB, and the apolipoprotein C3 -482 C>T polymorphisms on their association with coronary artery disease. Atherosclerosis. 2008;199:179–186. doi: 10.1016/j.atherosclerosis.2007.10.030.

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