Serum distribution of lipoprotein(a) in African Americans and Nigerians: Potential evidence for a genotype-environmental effect

Rotimi, Charles N.; Cooper, Richard S.; Marcovina, Santica M.; McGee, Daniel; Owoaje, Eme E.; Ladipo, Modupe M.

doi:10.1002/(sici)1098-2272(1997)14:2<157::aid-gepi5>3.0.co;2-4

Cited by 15 publications

(13 citation statements)

References 27 publications

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“…21 The mean lipid levels observed in this study are very similar to those reported in another Nigerian sample. 22 There was also no reported use of statins in this population.…”

Section: Nih-pa Author Manuscriptsupporting

confidence: 54%

“…21 The mean lipid levels observed in this study are very similar to those reported in another Nigerian sample. 22 There was also no reported use of statins in this population.The APOE and lipid interaction is being explored as an explanation to understand the risk of AD. This is not surprising because APOE plays a central role in cholesterol uptake and transport in the brain and is necessary for amyloid deposition in transgenic mice.…”

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confidence: 99%

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Cholesterol, APOE genotype, and Alzheimer disease

Hall¹,

Murrell²,

Ogunniyi³

et al. 2006

Neurology

121

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Objective-To examine the relationship between cholesterol and other lipids, APOE genotype, and risk of Alzheimer disease (AD) in a population-based study of elderly Yoruba living in Ibadan, Nigeria.Methods-Blood samples and clinical data were collected from Yoruba study participants aged 70 years and older (N = 1,075) as part of the Indianapolis-Ibadan Dementia Project, a longitudinal epidemiologic study of AD. Cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride levels were measured in fasting blood samples. DNA was extracted and APOE was genotyped. Diagnoses of AD were made by consensus using National Institute of Neurologic Disorders/Stroke-Alzheimer's Disease and Related Disorders Association criteria.Results-Logistic regression models showed interaction after adjusting for age and gender between APOE-ε4 genotype and biomarkers in the risk of AD cholesterol*genotype (p = 0.022), LDL*genotype (p = 0.018), and triglyceride*genotype (p = 0.036). Increasing levels of cholesterol and LDL were associated with increased risk of AD in individuals without the APOE-ε4 allele, but not in those with APOE-ε4. There was no significant association between levels of triglycerides and AD risk in those without APOE-ε4.Conclusions-There was a significant interaction between cholesterol, APOE-ε4, and the risk of Alzheimer disease (AD) in the Yoruba, a population that has lower cholesterol levels and lower incidence rates of AD compared to African Americans. APOE status needs to be considered when assessing the relationship between lipid levels and AD risk in population studies.The APOE-ε4 allele is a risk factor for Alzheimer disease (AD) in most populations. 1 The association between APOE-ε4 and AD for African Americans is less clear with some studies reporting no association 2 and others a weak association, 3 perhaps confined to the homozygous state. 4 We found no association between possession of the APOE-ε4 allele and AD in Yoruba residing in Nigeria. 5 There is increasing evidence that cholesterol plays a role in AD pathology, perhaps through its effects on amyloid deposition. 6 We have previously reported a significant interaction between APOE-ε4, cholesterol, and AD in African Americans in whom increasing We report on the interaction between APOE-ε4, cholesterol, and other lipids on the risk of AD in a population-based cohort of Yoruba who were evaluated as part of the IndianapolisIbadan Dementia Project. MethodsSince 1992, we have been conducting a comparative, community-based epidemiologic study of prevalence rates, incidence rates, and risk factors for AD in populations of African origin, elderly African Americans in Indianapolis, IN, and Yoruba living in Ibadan, Nigeria. Study participants have been evaluated at approximately 36-month intervals; this report focuses on the Ibadan site, which is located in the southwestern part of Nigeria where the predominant ethnic group is the Yoruba.In 2001, we conducted a two-stage study in which survivors of the 1992 cohort were ...

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“…21 The mean lipid levels observed in this study are very similar to those reported in another Nigerian sample. 22 There was also no reported use of statins in this population.…”

Section: Nih-pa Author Manuscriptsupporting

confidence: 54%

mentioning

confidence: 99%

Cholesterol, APOE genotype, and Alzheimer disease

Hall¹,

Murrell²,

Ogunniyi³

et al. 2006

Neurology

121

View full text Add to dashboard Cite

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“…One might be the presence of environmental factors in African populations as recently proposed. 52 Another could be the existence of (a) transacting factor(s) in Africans. This has also been suggested by Mooser et al 21 for African Americans.…”

Section: Discussionmentioning

confidence: 83%

Genetic control of lipoprotein(a) concentrations is different in Africans and Caucasians

et al. 1999

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Lipoprotein(a) (Lp(a)) represents a quantitative trait in human plasma associated with atherothrombotic disease. Large variation in the distribution of Lp(a) concentrations exists across populations which is at present unexplained. Sib-pair linkage analysis has suggested that the apo(a) gene on chromosome 6q27 is the major determinant of Lp(a) levels in Caucasians. We have here dissected the genetic architecture of the Lp(a) trait in Africans (Khoi San, South African Blacks) and Caucasians (Austrians) by family/sib-pair analysis. Heritability estimates ranged from h 2 = 51% in Blacks, h 2 = 61% in Khoi San, to h 2 = 71% in Caucasians. Analysis by a variance components model also demonstrated that the proportion of the total phenotypic variance explained by genetic factors is smaller in Africans (65%) than in Caucasians (74%). Importantly the sib-pair analysis clearly identified the apo(a) gene as the major locus in Caucasians which explained the total genetic variance. In the African samples the apo(a) gene accounted for only half the genetic variance. Together with previous results from population studies our data indicate that genetic control of Lp(a) levels seems to be distinctly different between Africans and Caucasians. In the former genetic factors distinct from the apo(a) locus and also non-genetic factors may play a major role.

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“…13,15,23 A comparative family study of Black South Africans, Khoi-San, and Europeans (Austrians) found that heritabilities of Lp(a) were considerably lower in Africans (h 2 ¼ 0.51) than in Europeans (h 2 ¼ 0.71) and that the LPA locus explained almost 100% of the genetic variance of the Lp(a) trait in the Austrians but less than 50% in the Africans. 13 These data suggested that the contribution of the apo(a) locus on the quantitative Lp(a) trait might be much weaker in Black people and that the higher Lp(a) in Africans might be explained by factors other than the LPA locus.…”

Section: Introductionmentioning

confidence: 99%

“…A population study conducted in African Americans and Nigerians indeed suggested a strong gene -environment interaction on Lp(a) in Black people. 23 To date, all family studies of apo(a)/Lp(a) in Black populations 13,15 have been performed in populations which are living in an environment that considerably differs from the situation in most of Africa, and which have a white admixture that may well reach over 20% in African Americans. 24,25 To get a better understanding of the genetic architecture of the LPA trait in Africans, we have performed a family study in an autochthonous Black African population from rural Western Central Africa.…”

Section: Introductionmentioning

confidence: 99%

Genetics of the Lp(a)/apo(a) system in an autochthonous Black African population from the Gabon

et al. 2005

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Plasma lipoprotein(a) (Lp(a)) is a quantitative trait associated with atherothrombotic disease in European and Asian populations. Lp(a) concentrations vary widely within and between populations, with Africans exhibiting on average two-to threefold higher Lp(a) levels and a different distribution compared to Europeans. The apo(a) gene locus on chromosome 6q26 -27 (LPA, MIM 152200) has been identified as the major quantitative trait locus (QTL) for Lp(a) concentrations in Europeans and populations of African descent (North American and South African Blacks) but data on autochthonous Black Africans are lacking. Here, we have analysed Lp(a) plasma concentrations, apo(a) isoforms in plasma and four polymorphisms in the LPA gene in 31 African families with 54 children from Gabon. Weighted midparent -offspring regression estimated a heritability h 2 ¼ 0.76. The correlation of Lp(a) levels associated with LPA alleles identical by descent (IBD) resulted in a heritability estimate of 0.801. Our data demonstrate that Lp(a) concentrations are highly heritable in a Central African population without admixture and high Lp(a) (median 43 mg/dl). LPA is the major QTL, explaining most or all of the heritability of Lp(a) in this population.

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Serum distribution of lipoprotein(a) in African Americans and Nigerians: Potential evidence for a genotype-environmental effect

Cited by 15 publications

References 27 publications

Cholesterol, APOE genotype, and Alzheimer disease

Cholesterol, APOE genotype, and Alzheimer disease

Genetic control of lipoprotein(a) concentrations is different in Africans and Caucasians

Genetics of the Lp(a)/apo(a) system in an autochthonous Black African population from the Gabon

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