Transcript APOE distribution in World populations

APOE distribution in World populations with new
data from the Indian and the British populations
P.P.Singh1, M. Singh1, S.S.Mastana2
1. Department of Human Biology, Punjabi University, Patiala, India.
2. Human Genetics Lab., Department of Human Sciences, Loughborough University, Loughborough, UK.
Introduction
Samples and Methods
Apolipoprotein E (APOE) is a 299- amino acid plasma glycoprotein
associated with very-low density lipoprotein (VLDL) and high-density
lipoprotein (HDL). It plays a major role in lipoprotein metabolism as a
ligand for receptors of the low density lipoprotein (LDL) receptor super
family.
Blood samples, with appropriate consent, were collected from
17 Indian caste and tribal populations and 8 populations from
Britain as part of our ongoing genetic studies. In all more than
2100 samples were analysed.
APOE allele frequencies
North India (Punjab) (Castes)- Ramdasias, Ramgarhias, Banias, Brahmins,Jatsikhs, Khatris,
Scheduled castes, Lobana, Rajput, Punjabi Hindus and Punjabi Sikhs
The human APOE gene is on chromosome 19. The structural gene is
polymorphic with three common alleles *E2, *E3, and *E4. These
isoforms differ in amino acid sequence at positions 112 and 158.
APOE*E3 contains cysteine at 112 and arginine at 158. APOE*E2 has
cysteine at both positions, and *E4 has arginine at both sites.
West India (Castes) Patels, Brahmins and Marathas
Central India (Tribes) -Baiga, Maria Gond and Koch.
Britain-NE England, NW Derbyshire, NE Derbyshire,South Derbyshire, Leicestershire,
Nottinghamshire, East Midlands and West Midlands
Polymorphism Analysis
Genotype/Phenotypes scored by IEF or PCR based methods.
Several studies have revealed that genetic polymorphism of APOE gene
affects the ApoE concentrations, total cholesterol, LDL cholesterol and
APO B levels. Compared to the wild type allele APO*E3, the APO*E2
is associated with decrease while the APO*E4 allele tends to increase the
TC, LDL-C and APO B levels.
Human populations show extensive allelic variation at this locus and the
gene has been associated with a variety of diseases. APOE*E4 allele is
associated with increased risk for cardiovascular disease, Alzheimer
disease, head trauma, cognitive decline and several other disorders and
traits including successful ageing.
Statistical Analysis
•Allele Frequencies: gene counting method
•Hardy-Weinberg equilibrium: chi-square method
•Correspondence analysis to assess genetic affinities.
•Longitude and latitudes was used for regression analysis.
•Allele frequency database on 272 World population/studies
was compiled and used for comparative analyses.
•Genetic distance, correspondence and regression analyses were
computed at major geographical and ethnic group levels.
•Spatial autocorrelation analyses.
Worldwide distribution of APOE*E4 allele
The main purpose of this study is to a) assess genetic variation at the
APOE locus in Indian and British samples and b) assess the extent and
phylogeographic patterns of APOE variation in world populations.
Results
All populations analysed were polymorphic. Tribal populations of India showed either
low frequency of APOE*E4 allele or its absence. Overall APOE*E4 frequency is low
in India, though cardiovascular diseases are very common in these populations. All
populations were in Hardy Weinberg equilibrium. Heterozygosity levels were higher
for British populations. Conclusive heterogeneity was observed within the British and
Indian populations.
q
6-12.5%
12.5-19%
19-25.5%
25.5-40%
World population databases show extreme ranges of allele frequencies. APOE*E3 is
highest in Indian and Asian populations while APOE*E2 and APOE*E4 are
prominent in different regional populations of Africa. Europe is the most extensively
studied region with 118 studies and shows a significant Latitudinal Cline of increasing
APOE*E4 and decreasing APOE*E3. This increasing cline was not observed in
Indian and Overall world populations. APOE*E2 revealed a statistically significant
decreasing cline towards North in Asia ( r = -0.511, y= -0.0013x+0.1053, df 55, p<
.05), which is not compatible with the coronary heart disease statistics in this
continent.
No Data
Worldwide latitudinal distribution of APOE
Fig.4. Worldwide distribution
APOE*E4
LatitudinalofVariation
in allele
World populations
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Spatial autocorrelation analysis depicts that the variation at this locus is influenced by
‘isolation by distance’ with a strong positive correlation for lower distances up to 1313
(distance class 2) kilometres. Correspondence analysis plot assigns most populations
according to major ethnic groupings. In this plot African populations are most isolated
and on periphery and European populations occupy a central position. Indians are in
between European and Asian populations.
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y = 38.763x + 0.5628
R2 = 0.0198
y = 4.2745x + 31.004
R2 = 7E-05
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E2
E3
E4
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Linear (E4)
y = -52.924x + 38.531
R2 = 0.0279
Linear (E3)
Linear (E2)
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Correspondence analysis plot of APOE allele frequencies
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Conclusions
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• Appreciable APOE genetic variation observed in Indian, British and world populations.
• Low frequency of APOE*E4 among Indian populations warrants further analyses and its association
with common diseases.
• Geographical cline of APOE*E4 is only significant in Europe. Natural Selection? Barriers?
• APOE is a good anthropogenetic marker and can be used to assess genetic relationships and disease
risk analyses.
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EIGENVECTOR 1
(Key to populations: Filled Pentagon-African, Green Triangle-South American, Red Triangle-North American, Light Blue
Diamonds-Asian, Blue Diamonds-European, Circle-Indian, and Purple Square-Australian)
For Details, E-mail: Dr P. P. Singh/Dr M. Singh ([email protected]) or Dr Sarabjit Mastana ([email protected])