Among ethnic groups, there are notable differences in the prevalence of hypoalphalipoproteinemia (defined as HDL cholesterol <40 mg/dl) . Asians and Indigenous American populations consistently have the lowest concentrations of HDL cholesterol both in population-based surveys and in cross-sectional studies. Hispanics are the fastest growing minority in the USA; from 1990 to 2000 this population increased by 58%, more than four times the national average of 13% . Hispanics will constitute up to a quarter of the US population by the year 2050. This ethnic group has a higher prevalence of diabetes, incidence of stroke and premature cardiovascular death than other populations . In this review, we examine the evidence regarding the increased susceptibility of Hispanic populations for hypoalphalipoproteinemia and discuss the contribution of genetic factors for this phenotype. The Native American ancestry of Hispanic populations provides an opportunity to assess the population-specific interactions between genes and the environment.
The epidemiological evidence
In the Global Burden of Disease Study, 31% of all deaths in 2000 in Latin American countries were attributed to cardiovascular diseases. The WHO predicts that the cardiovascular mortality rate in Latin America will increase by more than 60% between 2000 and 2020; in the developed world this figure is estimated to be 5% . In the USA, cardiovascular mortality is the leading cause of death in Hispanic men and women . The same is true for various Latin American populations . The association between atherogenic dyslipidemias (evaluated by the ratio apolipoprotein B/apolipoprotein A-I) and cardiovascular events has been confirmed in Latin American individuals ; the strength of the relationship is similar to that found in other areas of the world [8•]. Several groups have recognized that the expression of lipid abnormalities in Hispanics differs when compared with other ethnic groups [9,10]. Hypoalphalipoproteinemia is the most frequently found cardiovascular risk factor and its prevalence is higher than that seen in non-Hispanic individuals living in the same environment. The most recent NHANES data (1999–2002) show that the mean HDL cholesterol levels were lowest in Mexican Americans (45 ± 0.39 mg/dl in men and 52.9 ± 0.47 mg/dl in women) than in any other ethnic group . This difference was 5.6 mg/dl compared with non-Hispanic Blacks and 2.3 mg/dl compared with non-Hispanic Whites. The difference remains statistically significant among women (but not men) of different ethnic groups after adjusting for age. The low-HDL cholesterol levels reported in Hispanics in NHANES 1999–2002 are in accordance with the findings of NHANES 1988–1994. The same phenomenon has been reported in the US studies involving Hispanic adults and elders. In both the San Luis Rio Valley Study and the San Antonio Heart Study, lower HDL cholesterol levels were found in Mexican American participants compared with Caucasian controls [12,13]. Bermudez et al.  reported the same observation when comparing 490 Hispanic and 163 non-Hispanic White elders. The HDL cholesterol concentrations were statistically lower in Hispanics even after adjusting for age, sex, years-of-education, smoking status, waist circumference, BMI, and use of antihyperlipidemic drugs. A summary of several studies that have reported mean HDL cholesterol levels in adults from different ethnic backgrounds is shown in Table 1. Thus, hypoalphalipoproteinemia appears to be a phenotypic trait associated with Hispanic ethnicity.
The susceptibility of Hispanic populations to hypoalphalipoproteinemia has been detected in several Latin American population surveys. The prevalence of low HDL cholesterol has been described in two Mexican population-based surveys [19,20]. The National Survey of Chronic diseases (1993–1994) included results from 15 607 adults aged 20–69 years from 417 cities in Mexico . Of the 2256 individuals who provided fasting blood samples, the mean concentration of HDL cholesterol was 38.3 ± 9.5mg/dl. Close to 50% of the study group (58.8% in men and 40.8% in women) were found to have hypoalphalipoproteinemia (HDL cholesterol <35 mg/dl). If the low HDL cholesterol is defined as a concentration below 40 mg/dl in both genders, this figure jumps to 61%. Sixty-two percent of those with low-HDL cholesterol had hypertriglyceridemia (>150 mg/dl) and the remaining 38% had isolated hypoalphalipoproteinemia. These results were replicated in a second population-based survey carried out six years later. The Mexican National Health USA Survey (2000) included results from approximately 44 000 individuals over the age of 20  from both urban and rural regions. Of these, 2351 persons provided fasting blood samples for lipid analysis. Here again the mean concentration of HDL cholesterol was low, 38.4 mg/dl (95%CI = 37.2, 39.5). Hypoalphalipoproteinemia (HDL cholesterol <40 mg/dl) was the most prevalent dyslipidemia, present in 64.7% (95%CI = 58.7–70.8) of women and 61.4% (95%CI = 54.4–68.3) of men. Remarkably, the prevalence of hypoalphalipoproteinemia was not significantly different between adults living in rural or urban settings (for women 63.1 vs. 66.3%, for men 59.2 vs. 63.7% respectively).
The prevalence of hypoalphalipoproteinemia in Mexican adults is higher than that found in Caucasians. Using 1999–2000 NHANES data, with less strict thresholds (as defined by the National Cholesterol Education Program (NCEP) less than 40 mg/dl for men and <50 mg/dl for women), hypoalphalipoproteinemia was present in 36.6 and 43.4% of Hispanic men and women, respectively . Even higher percentages have been found in studies from the UK and the Netherlands [26,27]. The high figures reported for Mexico have only been superseded by the estimates reported for an urban cohort in Turkey (82% of men and 50% of women using the NCEP criteria).
The findings of the two Mexican National Surveys coincide with the results of the Mexico City Diabetes Study. In 1990–1992, 2282 adults (aged 35–64 years) from six low-income neighborhoods in Mexico City were enrolled in this study. Follow up results for the period 1997–1999 (n = 1754) have been published . The prevalence of low-HDL cholesterol (<40 mg/dl in men and <50 mg/dl in women) increased from 88.6% (95%CI 86.3–90.5) to 92.1% (95%CI 89.9–93.9) in men and from 94.4% (95%CI 92.9–95.5) to 96.6% (95%CI 95.3–97.5) in women. In addition, the cardiovascular risk profile of individuals in the 1990–1992 Mexico City Study has been compared with that of the Mexican-American participants in the San Antonio Heart Study . Individuals from Mexico City had significantly lower HDL cholesterol (P < 0.001) and higher triglyceride levels (P < 0.001) than their Texan counterparts. These results probably reflect differences in dietary habits between the two populations; the Mexico City inhabitants consuming a diet lower in fat but higher in carbohydrates. This highlights the influence of environmental factors on the expression of a particular genetic trait.
Surveys carried out in other Latin American countries are in accordance with the increased susceptibility of Hispanic individuals for low-HDL cholesterol and metabolic-syndrome traits. Studies performed in Colombia , Venezuela , Argentina , El Salvador , Brazil  and simultaneously in seven Latin American cities [34•], primarily to measure the prevalence of the metabolic syndrome, have reported a high prevalence of hypoalphalipoproteinemia. In particular, a Brazilian population-based study measured the prevalence of diabetes and related-risk factors among 1494 adults (18–59 years) living in the small community of Bambuí : using the NCEP criteria, a prevalence of 50% was reported.
Hence, low-HDL cholesterol is common in Hispanic populations. Clearly, further population-based studies and national surveys are necessary, especially as Latin American populations are undergoing an epidemiological transition [35•].
Factors influencing low-HDL cholesterol in Hispanic populations
The high prevalence of hypoalphalipoproteinemia encountered in Hispanics is a result of the interaction of environmental and genetic factors. On average, US Hispanics have lower intakes of total fat and higher intakes of carbohydrates compared with the US Caucasians . The same is true for the food pattern reported in México and other Latin American countries [37•]. Furthermore, Hispanics have a high prevalence of obesity, hypertriglyceridemia and the metabolic syndrome traits, all of which have a negative effect on HDL cholesterol concentrations . These associations complicate the identification of an independent contribution of ethnicity to the pathogenesis of this condition. However, there are two observations that suggest that Hispanic ancestry predisposes to low-HDL cholesterol. Firstly, in the USA metabolic syndrome cases, Hispanics (especially women) are the group with the highest prevalence of hypoalphalipoproteinemia . The prevalence is higher still in Mexican adults; in the Mexico City Study, hypoalphalipoproteinemia is a constant feature of the metabolic syndrome (men 88.6% and women 94.2%). This percentage is significantly greater than that found in Caucasians from San Antonio (58.4%) and from Spain (30.8%) . Secondly, 18.6% of Mexican adults have isolated hypoalphalipoproteinemia, a condition in which low-HDL cholesterol is not related to hypertriglyceridemia. The prevalence in young men (23.1%) is similar to that observed in men aged 50–59 years (26.5%). In addition, 43% of this group are lean and without markers of insulin resistance . These two observations endorse the search for a genetic predisposition for low-HDL cholesterol in this population.
The term Hispanic refers to people born in a country that was ‘conquered’ by Spaniards and for whom Spanish is the mother tongue . Significant genetic (in particular variability in genetic admixture) and cultural diversity is evident in this ethnic group. Even the Native American ancestry cannot be considered a homogeneous genetic background . However, if a genetic predisposition for hypoalphalipoproteinemia exists, it should be associated with the Native American heritage. Several groups have studied the lipid profile of American Indians from Canada, the USA, México and South America [42–44]. Most reports found low mean HDL cholesterol levels in these groups living in their natural settlements. However, a remarkable increment (∼31%) in HDL cholesterol occurs when they are exposed to a high-fat diet (from 32 to 42 mg/dl), as have been reported in Tarahumara and Pima Indians . More recent reports including indigenous populations living in Northern Mexico have found a high prevalence of hypoalphalipoproteinemia (53.8% in men and 39.5% in women, using the NCEP criteria) . This data supports the contention that the susceptibility for hypoalphalipoproteinemia in Hispanics may come from their Native American heritage.
HDL-genetic studies in hispanics
Twin studies suggest that close to 50% of the variation of HDL cholesterol levels are genetically determined . More than 50 genes have been reported to be associated with HDL based on human and animal studies . The genes encoding apolipoprotein AI, lecithin:cholesterol acyltransferase, cholesterol ester transfer protein, hepatic lipase and the ATP binding cassette protein A1(ABCA1) are key players in HDL metabolism and variations of these genes have been shown to alter HDL cholesterol levels . The number of identified loci and genes has recently increased as a result of the publication of five high-density genome-wide association studies [49•–53•]. However, the pathophysiological mechanism by which the majority of the genes and loci are linked with variations in HDL cholesterol levels remain unknown. Despite the large number of identified loci, the SNPs that meet the genome-wide level of significance, including the previously identified genes, explain only 5–8% of the interindividual variation in HDL cholesterol . Current knowledge of the genetics of HDL accounts for only a small fraction of the total-genetic contribution.
The evidence discussed earlier originates primarily from Caucasian cohorts. Hispanics have been included in only one of the five genome-wide scans cited earlier. The majority of the genetic studies including Hispanics or Native Americans have focused on other metabolic syndrome traits [55,56]. However, there are several reports describing loci that affect HDL cholesterol levels in Mexican-Americans and in kindred from Mexico [57,58]. Also, several groups have analyzed the effects of CETP, LPL, LIPC, ABCG5/G8 and APOC3 variants on HDL levels in multiethnic cohorts including Hispanics or Native Americans [59,60••].
Certain population-specific genes may alter the disease susceptibility of Hispanics by influencing lipid profiles, for example, the ε2 allele of APOE is very rare in Native American populations ; in Latin American cohorts, the prevalence of the ε2 allele is a marker of admixture with Europeans. A more noteworthy allele is the (Arg230Cys) variant of the ABC-A1 gene. Villarreal-Molina et al. [60••,61•] have shown that this variant is strongly associated with hypoalphalipoproteinemia in two different Mexicans cohorts. The R230C/C230C genotypes were significantly more frequent in the low HDL cholesterol (≤10 percentile of the Mexican population) than in the high HDL cholesterol group (≥90 percentile) (45 vs. 2.9%, P = 0.00006, P = 0.0005 after adjusting for admixture). Although the R230C variant has not been functionally tested, it is very likely that this change results in decreased activity of the transporter as supported by computer modeling. An additional finding was that the R230C variant appears to be specific for the Mexican Amerindian populations. The C230 allele had a frequency of 0.109 in mestizos; as expected, this was half the prevalence found in Mexican native groups (0.28 in Mayans, 0.214 in Purepechas, 0.203 in Yaquis and 0.179 among Teenek). In contrast, the C230 allele has not been found in African, European, Chinese, South Asian or Inuit populations. R230C seems to be exclusive for Amerindian and Amerindian-derived populations such as Mexican Mestizos. These results have been confirmed by Kooner et al. [49•]. The authors did a three-stage association study to identify genetic polymorphisms affiliated with metabolic syndrome traits. In stage 2, 900 SNPs were tested against HDL cholesterol in 4568 individuals from four cohorts: 859 European women, 1181 Indian Asian women, 1560 Mexican women and 968 Mexican men. For HDL cholesterol, nine SNPs were significantly associated with HDL cholesterol levels. Six of these were in or around the CETP gene, one was in the LPL gene, one was in the LIPC gene and one was a nsSNP in ABCA1 (rs9282541, Arg230Cys). This ABC-A1 variant was exclusively found in the Mexican cohort. Its presence has a significant negative effect on HDL cholesterol levels (−4.2%). We believe that this is a relevant finding that may be a result of a survival effect. This variant may be preserved in these populations because it provided some advantage in the past (i.e. allowing the cells to preserve cholesterol inside during times of famine). No similar phenomenon has been reported between an ethnic-specific variant and hypoalphalipoproteinemia.
Hypoalphalipoproteinemia is a common feature of Hispanic and Native American populations. The observations summarized here provide strong arguments for the inclusion of Hispanic and Native American individuals in future genome-wide scans. The assessment of the genetic and environmental determinants of hypoalphalipoproteinemia in populations with Native American origin provides an opportunity to assess the population-specific interactions between genes and the environment. This is a unique opportunity to do nutrigenomic studies, as these populations are undergoing an epidemiological transition. The high prevalence of the R230C allele of ABC-A1 in populations of Native American origin may be the result of a survival process (Fig. 1). However, after major changes in environmental factors, this variant may have become a susceptibility factor for hypoalphalipoproteinemia and possibly other metabolic traits and atherosclerosis.
The authors would like to express their gratitude to the collaborators that have participated in the ABC-A1 studies. Of special mention is the invariably stimulating collaboration with David Cox, PhD (Perlegen laboratories). We are also grateful to Ivan Dario Sierra MD and Nestor Caceres, MD for providing data (from Colombia and Salvador, respectively) for the preparation of this review.
Some of the research presented here was supported by grants from the Consejo Nacional de Ciencia y Tecnologıa (CONACyT) and by Dirección General de Asuntos del Personal Académico (DGAPA) of the Universidad Nacional Autónoma de México (UNAM).
References and recommended reading
Papers of particular interest, published within the annual period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Additional references related to this topic can also be found in the Current World Literature section in this issue (pp. 141–142).
1 Kuller LH. Ethnic differences in atherosclerosis, cardiovascular disease and lipid metabolism. Cur Opin Lipidol 2004; 15:109–113.
2 Palloni A, Morenoff JD. Interpreting the paradoxical in the hispanic paradox: demographic and epidemiologic approaches. Ann N Y Acad Sci 2001; 954:140–174.
3 Miech RA, Kim J, McConnell C, Hamman RF. A growing disparity in diabetes-related mortality U.S. trends, 1989–2005. Am J Prev Med 2009; 36:126–132.
4 Yusuf S, Reddy S, Ounpuu S, et al
. Global Burden of Cardiovascular Diseases. Part II: Variations in cardiovascular disease by specific ethnic groups and geographic regions and prevention strategies. Circulation 2001; 104:2855–2864.
5 Mensah GA, Mokdad AH, Ford ES, et al
. State of disparities in cardiovascular health in the United States. Circulation 2005; 111:1233–1241.
6 Lopez-Jaramillo P. Defining the research priorities to fight the burden of cardiovascular diseases in Latin America. J Hypertens 2008; 26:1886–1889.
7 Lanas F, Avezum A, Bautista L, et al
. Risk factors for acute myocardial infarction in Latin America. The INTERHEART Latin American Study. Circulation 2007; 115:1067–1074.
8• McQueen MJ, Hawken S, Wang X, et al
. Lipids, lipoproteins, and apolipoproteins as risk markers of myocardial infarction in 52 countries (the INTERHEART study): a case-control study. Lancet 2008; 372:224–233. The population-attributable risk of the ratio apolipoprotein B/apolipoprotein A-I for a cardiovascular event is described in a large case-control study including subjects of several ethnic groups.
9 Carroll M, Sempos C, Fulwood R, et al
. Serum lipids and lipoproteins of Hispanics, 1982–84. Vital Health Stat 1990; 240:1–65.
10 Harris-Hooker S, Sanford GL. Lipids, lipoproteins and coronary heart disease in minority populations. Atherosclerosis 1994; 108(Suppl):S83–S104.
11 Carroll MD, Lacher DA, Sorlie PD, et al
. Trends in serum lipids and lipoproteins of adults 1960–2002. JAMA 2005; 294:1773–1781.
12 Swenson CJ, Trepka MJ, Rewers MJ, et al
. Cardiovascular disease mortality in Hispanics and non-Hispanic Whites. Am J Epidemiol 2002; 156:919–928.
13 Hunt KJ, Resendez RG, Williams K, et al
. All-cause and cardiovascular mortality among Mexican-American and non-Hispanic White older participants in the San Antonio Heart Study- evidence against the ‘Hispanic paradox’. Am J Epidemiol 2003; 158:1048–1057.
14 Bermudez O, Velez-Carrasco W, Schaefer EJ, Tucker KL. Dietary and plasma lipid, lipoprotein, and apolipoprotein profiles among elderly Hispanics and non-Hispanics and their association with diabetes. Am J Clin Nutr 2002; 76:1214–1221.
15 Leino A, Impivaara O, Kaitsaari M, et al
. Serum concentrations of apolipoprotein A-I, apolipoprotein B and lipoprotein (a) in a population sample. Clin Chem 1995; 41:1633–1636.
16 Houterman S, Verschuren WMM, Boersma-CobbaertF CM, et al
. Trends in total and high density lipoprotein cholesterol and their determinants in the Netherlands between 1993 and 1997. Int J Epidemiol 2001; 30:1063–1070.
17 Bruckert E. Epidemiology of low HDL-cholesterol: results of studies and surveys. Eur Heart J Supplements 2006; 8(Suppl F):F17–F22.
18 De Azeredo Passos VM, Barrero SM, Diniz LM, et al
. Type 2 diabetes: prevalence and associated factors in a Brazilian community- the Bambuí health and aging study. Sao Paulo Med J 2005; 123:66–71.
19 Aguilar-Salinas CA, Olaiz G, Valles V, et al
. High prevalence of low HDL cholesterol concentrations and mixed hyperlipidemia in a Mexican nationwide survey. J Lipid Res 2001; 42:1298–1307.
20 Barquera S, Flores M, Olaiz-Fernández, et al.
Dyslipidemias and obesity in Mexico. Salud Pública Mex 2007; 49:S338–S347.
21 Choudhury S, Ueshima H, Kita Y, et al
. Alcohol intake and serum lipids in a Japanese population. Int J Epidemiol 1994; 23:940–947.
22 Fong PC, Tam SC, Tai Y, et al
. Serum lipid and apolipoprotein distribution in Hong Kong Chinese. J Epidemiol Community Health 1994; 48:355–359.
23 Mahley RW, Erhan-Palaoglu K, Atak Z, et al
. Turkish Heart Study: lipids,lipoproteins and apolipoproteins. J Lipid Res 1995; 36:839–859.
24 Rodriguez-Moran M, Guerrero-Romero F, Brito-Zurita O, et al
. Cardiovascular risk factors and acculturation in Yaquis and Tepehuanos Indians from Mexico. Arch Med Res 2008; 39:352–357.
25 Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults. JAMA 2002; 287:356–359.
26 Patel JV, Kirby M, Hughes EA. The lipid audit: analysis of lipid management in two centers in Britain 2003. Br J Cardiol 2004; 11:214–217.
27 Verschuren WMM, Boerma GJ, Kromhout D. Total and HDL-cholesterol in the Netherlands: 1987–1992. Levels and changes over time in relation to age, gender and educational level. Int J Epidemiol 1994; 23:948–956.
28 Lorenzo C, Gonzalez-Villalpando C, Williams J, et al
. The prevalence of the metabolic syndrome did not increase in Mexico City between 1990–1992 and 1997–1999 despite more central obesity. Diabetes Care 2005; 28:2480–2485.
29 Mitchell BD, González Villalpando C, Arredondo Pérez B, et al
. Myocardial Infarction and cardiovascular risk factors in Mexico City and San Antonio, Texas. Arterioscler Thromb Vasc Biol 1995; 15:721–725.
30 Mendevil CO, Sierrea ID, Pérez CE. Valoración del riesgo cardiovascular global y prevalencia de dislipidemia según los criterios del NCEP-ATP-III en una población adulta de Bogotá, Columbia. Clin Invest Arterioscl 2004; 16:99–107.
31 Ryder E, Silva E, Sulbarán T, et al
. Black Hispanics have a worse cardiovascular risk profile than mixed Hispanics in Venezuela. Invest Clin 2007; 48:45–55.
32 Ferrante D, Virgolini M. Risk factor's national survey 2005:Main results. Prevalence of the cardiovascular risk factors in Argentina. Rev Argent Cardiol 2007; 75:20–29.
33 Juarez X, Benitez J, Quezada-Galdamez R, et al
. Prevalence of the metabolic syndrome in an urban population of San Salvador. Revista de la Asociación Latinoamericana de Diabetes 2006; 14:16–20.
34• Schargrodsky H, Hernandez-Hernandez R, Marcet Champagne B, et al
. CARMELA: assessment of cardiovascular risk in seven Latin American cities. Am J Med 2008; 121:58–65. The first population-based study that describes the prevalence of cardiovascular risk factor in several Latin American cities.
35• Stevens G, Dias RH, Kevin JA, et al.
Characterizing the epidemiological transition in Mexico: National and subnational burden of diseases, injuries, and risk factors. PLoS Med 5: e125. doi:10.1371/journal.pmed.0050125.
A careful joint analysis of epidemiological data that demonstrates the epidemiological transition that is occurring in México.
36 Rodriguez C, Pablos-Méndez A, Palmas W, et al
. Comparison of modifiable determinants of lipids and lipoprotein levels among African-Americans, Hispanics, and Non-Hispanic Caucasians > or =65 years of age living in New York City. Am J Cardiol 2002; 89:178–183.
37• Barquera S, Hernandez-Barrera L, Tolentino ME, et al
. Energy intake from beverages is increasing among Mexican adolescents and adults. J Nutr 2008; 138:2454–2461. A description of the dietary habits (with emphasis on the consumption of beverages) in a Mexican population-based nationwide survey.
38 Caballero AE. Type 2 diabetes in the Hispanic or Latino population: challenges and opportunities. Curr Opin Endocrinol Diabetes Obes 2007; 14:151–157.
39 Lorenzo C, Serrano-Ríos M, Martinez-Larrad M, et al
. Geographic variations of the International Diabetes Federation and the National Cholesterol Education Program–Adult Treatment Panel III definitions of the metabolic syndrome in nondiabetic subjects. Diabetes Care 2006; 29:685–691.
40 Caballero AE. Diabetes in the Hispanic or Latino population: genes, environment, culture, and more. Curr Diab Rep 2005; 5:217–225.
41 Price A, Patterson N, Yu F, et al
. A genomewide admixture map for Latino populations. Am J Hum Genet 2007; 80:1024–1036.
42 Merchant AT, Anand SS, Kelemen LE, et al
. Carbohydrate intake and HDL in a multiethnic population. Am J Clin Nutr 2007; 85:225–230.
43 Welty TK, Lee ET, Yeh J, et al
. Cardiovascular disease risk factors among American Indians. The Strong Heart Study. Am J Epidemiol 1995; 142:269–287.
44 Aguilar CA, Talavera G, Ordovas JM, et al
. The apolipoprotein E4 allele is not associated with an abnormal lipid profile in a Native American population following its traditional lifestyle. Atherosclerosis 1999; 142:409–414.
45 McMurry MP, Connor WE, Cerqueira MT. Dietary cholesterol and the plasma lipids and lipoproteins in the Tarahumara Indians: a people habituated to a low cholesterol diet after weaning. Am J Clin Nutr 1982; 35:741–744.
46 Kathiresan S, Manning A, Demissie S, et al
. A genome-wide association study for blood lipid phenotypes in the Framingham Heart Study. BMC Medical Genetics 2007; 8(Suppl 1):S1–S17.
47 Holleboom AG, Vergeer M, Hovingh K, et al
. The value of HDL genetics. Cur Opin Lipidol 2008; 19:385–394.
48 Scanu AM, Edelstein C. HDL: bridging past and present with a look at the future. FASEB J 2008; 22:4044–4054.
49• Kooner J, Chambers JC, Aguilar-Salinas CA, et al
. Genome-wide scan identifies variation in MLXIPL
associated with plasma triglycerides. Nat Genet 2008; 40:149–151. The only high-density genome-wide association study related to lipid disorders in which a Hispanic population was included.
50• Willer C, Sanna S, Jackson A, et al
. Newly identified loci that influence lipid concentrations and risk of coronary heart disease. Nat Genet 2008; 40:161–169. Several newly identified loci linked with HDL cholesterol levels are reported in an European study including 6068 individuals, originally collected to identify diabetes genes.
51• Kathiresan S, Melander O, Guiducci C, et al
. Six new loci associated with blood low density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans. Nat Genet 2008; 40:189–197. Six newly identified chromosomal regions, one with HDL cholesterol (1q42 in GALNT2) and five with triglycerides are reported in this genome-wide association study.
52• Kathiresan S, Willer CJ, Peloso GM, et al
. Common variants at 30 loci contribute to polygenic dyslipidemia. Nat Genet 2009; 41:56–65. A genome-wide association study that identifies association between the ANGPTL4, FADS1-FADS2-FADS3, HNF4A, LCAT, PLTP and TTC39B genes and HDL cholesterol levels in a large number of cases and controls.
53• Aulchenko YS, Ripatti S, Lindqvist I, et al
. Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts. Nat Genet 2009; 41:47–55. A genome-wide association study that describes the association between 22 loci and several lipid traits in a large number of cases and controls. However, genetic risk scores based on lipid loci explain up to 4.8% of variation in lipids.
54 Hunt KJ, Lehman DM, Arya R, et al
. Genome-wide linkage analyses of type 2 diabetes in Mexican Americans: the San Antonio Family Diabetes/Gallbladder Study. Diabetes 2005; 54:2655–2662.
55 Santamaría A, Diego VP, Almasy L, et al
. Quantitative trait locus on chromosome 12q14.1 influences variation in plasma plasminogen levels in the San Antonio Family Heart Study. Hum Biol 2007; 79:515–523.
56 Arya R, Duggirala R, Almasy L, et al
. Linkage of high-density lipoprotein-cholesterol concentrations to a locus on chromosome 9p in Mexican Americans. Nat Genet 2002; 30:102–105.
57 Canizales S, Aguilar Salinas CA, Auron Gomez M, et al
. Locus on chromosome 6p linked to elevated HDL-C serum levels, and to protection against premature atherosclerosis in a kindred with familial hypercholesterolemia. Circ Res 2003; 92:569–576.
58 Humphries SE, Berglund L, Isasi CR, et al
. Loci for CETP, LPL, LIPC, and APOC3 affect plasma lipoprotein size and sub-population distribution in Hispanic and non-Hispanic white subjects: the Columbia University BioMarkers Study. Nutr Metab Cardiovasc Dis 2002; 12:163–172.
59 Junyent M, Tucker KL, Smith CE, et al.
The effects of ABCG5/G8
polymorphisms on plasma HDL cholesterol concentrations depend on smoking habit in the Boston Puerto Rican Health Study. J Lipid Res 2008 [Epub ahead of print]
60•• Villarreal-Molina MT, Aguilar-Salinas CA, Rodríguez-Cruz M, et al
. The ABCA1 R230C variant affects HDL cholesterol levels and body mass index in the Mexican population: association with obesity and obesity-related comorbidities. Diabetes 2007; 56:1881–1887. This study reports the ethnic-specific association of the R230C variant of the ABC-A1 gene with hypoalphaliproteinemia in Mexican Mestizos and several Native American populations.
61• Villarreal-Molina MT, Flores-Dorantes MT, Arellano-Campos O, et al
. Association of the ABCA1 R230C variant with early-onset type 2 diabetes in the Mexican population. Diabetes 2008; 57:509–513. The confirmation of the association of the R230C variant of the ABC-A1 gene with hypoalphaliproteinemia in a different Mexican cohort. In addition, an association with early onset type 2 diabetes is reported here.