Evolutionary Genetics of Coronary Heart Disease

Ding, Keyue; Kullo, Iftikhar J.

doi:10.1161/circulationaha.108.809970

Cited by 38 publications

(26 citation statements)

References 97 publications

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“…The affluent environment of modern America is however markedly different from the traditional, adverse conditions of tropical Africa in which the genes were selected for. It has been proposed that common phenotypes in affluent environments, such as obesity and systemic inflammation, can be due to gene-environment interaction, a notion that is indirectly supported by our finding that a West-African population residing in its original environment has low BMI and low CRP [47]–[49].…”

Section: Discussionsupporting

confidence: 77%

Low C-Reactive Protein Levels in a Traditional West-African Population Living in a Malaria Endemic Area

Eriksson

Bodegom²,

May³

et al. 2013

PLoS ONE

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BackgroundC-reactive protein (CRP) levels are reported to be elevated in populations of African descent living in affluent environments compared to populations of European ancestry. However, the natural history of CRP levels in populations of African descent living under adverse environments remains largely unknown.MethodsCRP levels were measured with a high sensitivity assay in 624 apparently healthy individuals who contributed blood as part of a study on innate immune responsiveness in a traditional Ghanaian population living under adverse environmental conditions in a malaria endemic area. As a comparison, we included CRP measurements from 2931 apparently healthy individuals from the Dutch population that were included in the same batch of CRP analyses. Associations between CRP and body mass index (BMI), immune responsiveness, and P. falciparum parasitaemia were investigated.ResultsIn an age- and sex-adjusted model, CRP levels were 0.54 mg/L lower in the Ghanaian compared to the Dutch cohort (1.52 vs. 0.98 mg/L, p<0.001). When accounting for the substantially higher average BMI in the Dutch compared to the Ghanaians (25.6 vs. 18.4 kg/m2) the difference in CRP levels disappeared. BMI associated positively with CRP in the Dutch but not in the Ghanaians. In individuals with an acute phase response, CRP levels were higher in the Ghanaian compared to the Dutch cohort (24.6 vs. 17.3 mg/L, p = 0.04). Levels of CRP were positively related to immune responsiveness and P. falciparum parasitaemia (all p<0.001) among Ghanaians.ConclusionsOur study demonstrates that West-Africans do not exhibit an inherently high inflammatory state. The role of genes, environment and gene-environment interaction in explaining reports of elevated CRP levels in populations of African ancestry when compared to other ethnicities living in affluent environments thus merits further investigation.

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Section: Discussionsupporting

confidence: 77%

Low C-Reactive Protein Levels in a Traditional West-African Population Living in a Malaria Endemic Area

Eriksson

Bodegom²,

May³

et al. 2013

PLoS ONE

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“…The reason for the relatively high prevalence of genetic variants that lead to FH is not clear, although it is speculated that the variants may have been advantageous from an evolutionary standpoint. 1–3 The first patients with FH were described almost 80 years ago by the Norwegian physician Muller. 4,5 Twenty-five years later, a single-gene codominant inheritance was postulated by Khachadurian 6 based on segregation analysis in Lebanese families.…”

Section: Historical Aspectsmentioning

confidence: 99%

My Approach to the Patient With Familial Hypercholesterolemia

Safarova

Kullo

2016

Mayo Clinic Proceedings

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Familial hypercholesterolemia (FH), a relatively common Mendelian genetic disorder, is associated with a dramatically increased lifetime risk of premature atherosclerotic cardiovascular disease due to elevated plasma low-density lipoprotein cholesterol (LDL-C) levels. The diagnosis of FH is based on clinical presentation or genetic testing. Early identification of patients with FH is of great public health importance because preventive strategies can lower the absolute lifetime cardiovascular risk and screening can detect affected relatives. However, low awareness, detection, and control of FH pose hurdles in the prevention of FH-related cardiovascular events. Of the estimated 0.65 million to 1 million patients with FH in the United States, less than 10% carry a diagnosis of FH. Based on registry data, a substantial proportion of patients with FH are receiving no or inadequate lipid-lowering therapy. Statins remain the mainstay of treatment for patients with FH. Lipoprotein apheresis and newly approved lipid-lowering drugs are valuable adjuncts to statin therapy, particularly when the LDL-C–lowering response is suboptimal. Monoclonal antibodies targeting proprotein convertase subtilisin/kexin type 9 provide an additional approximately 60% lowering of LDL-C levels and are approved for use in patients with FH. For homozygous FH, 2 new drugs that work independent of the LDL receptor pathway are available: an apolipoprotein B antisense oligonucleotide (mipomersen) and a microsomal triglyceride transfer protein inhibitor (lomitapide). This review attempts to critically examine the available data to provide a summary of the current evidence for managing patients with FH, including screening, diagnosis, treatment, and surveillance.

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“…Many functional variants have been identified at this locus. Missense mutations that increase PCSK9 activity are associated with hypercholesterolemia [40], whereas loss-of-function mutations associate with lower LDL-C concentrations [41 •• ]. Sequencing 28 kbp of the PCSK9 gene in 24 African–Americans and 23 European Amer-icans allowed detection of significant signals of positive selection based on Fay and Wu’s H, Tajima’s D, Fst and long-range haplotype methods in both populations [41 •• ].…”

Section: Adaptive Genetic Variants and Risk Of Dyslipidemia And Heartmentioning

confidence: 99%

Adaptive genetic variation and heart disease risk

Parnell

Lee

Lai

2010

Current Opinion in Lipidology

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Purpose of review Obesity, dyslipidemia and cardiovascular disease are complex and determined by both genetic and environmental factors and their inter-relationships. Many associations from genome-wide association studies and candidate gene approaches have described a multitude of polymorphisms associating with lipid and obesity phenotypes but identified genetic variants account for only a small fraction of phenotypic variation. Recent findings That many genotype–phenotype associations involve variants under positive selection and that those variants respond to environmental cues together suggest prominent roles for both genetic adaptation and their interactions with the environment. Adaptive genetic variations interacting with environment modulate disease susceptibility but the level to which those variants contribute to dyslipidemia and obesity and how environmental factors, especially diet, alter the genetic association is not yet completely known. Summary It is evident that genetic variants under positive selection make important contributions to obesity and heart disease risk. Advances in resequencing the entire human genome will enable accurate identification of adaptive variants. Considering interactions between environmental factors and genotypes will empower both genome-wide association studies and characterization of the relationship between positive selection and the obese and dyslipidemic conditions.

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Evolutionary Genetics of Coronary Heart Disease

Cited by 38 publications

References 97 publications

Low C-Reactive Protein Levels in a Traditional West-African Population Living in a Malaria Endemic Area

Low C-Reactive Protein Levels in a Traditional West-African Population Living in a Malaria Endemic Area

My Approach to the Patient With Familial Hypercholesterolemia

Adaptive genetic variation and heart disease risk

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