APOE distribution in World populations with new data from the Indian and the British populations

1
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 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. 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. APOEE3 contains cysteine
at 112 and arginine at 158. APOEE2 has cysteine
at both positions, and E4 has arginine at both
sites. 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 APOE3, the APOE2 is associated
with decrease while the APOE4 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. APOEE4 allele is
associated with increased risk for cardiovascular
disease, Alzheimer disease, head trauma,
cognitive decline and several other disorders and
traits including successful ageing. 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.

• Samples and Methods
• 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.
• North India (Punjab) (Castes)- Ramdasias,
  Ramgarhias, Banias, Brahmins,Jatsikhs, Khatris,
  Scheduled castes, Lobana, Rajput, Punjabi Hindus
  and Punjabi Sikhs
• 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.
• 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.

APOE allele frequencies
Worldwide distribution of APOEE4 allele
Results All populations analysed were
polymorphic. Tribal populations of India showed
either low frequency of APOEE4 allele or its
absence. Overall APOEE4 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. World
population databases show extreme ranges of
allele frequencies. APOEE3 is highest in Indian
and Asian populations while APOEE2 and APOEE4
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 APOEE4 and
decreasing APOEE3. This increasing cline was
not observed in Indian and Overall world
populations. APOEE2 revealed a statistically
significant decreasing cline towards North in
Asia ( r -0.511, y -0.0013x0.1053, df 55, plt
.05), which is not compatible with the coronary
heart disease statistics in this continent.
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.
Latitudinal Variation in World populations
Fig.4. Worldwide distribution of APOEE4 allele

Correspondence analysis plot of APOE allele
frequencies

• Conclusions
• Appreciable APOE genetic variation observed in
  Indian, British and world populations.
• Low frequency of APOEE4 among Indian
  populations warrants further analyses and its
  association with common diseases.
• Geographical cline of APOEE4 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.

(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
(s_puneet_at_angelfire.com) or Dr Sarabjit Mastana
(S.S.Mastana_at_lboro.ac.uk)