APOE distribution in world populations with new data from India and the UK

The APOE gene and its protein product is associated with a number of plasma proteins like very-low density lipoprotein (VLDL), high density lipoprotein (HDL) chylomicrons, chylomicron remnants, and plays a crucial role in lipid metabolism. The APOE gene is polymorphic and common alleles (*E2, *E3 and *E4) have been associated with a number of common and complex diseases in different populations. Due to their crucial role in metabolism and clinical significance, it is imperative that allelic variation in different populations is analysed to evaluate the usage of APOE in an evolutionary and clinical context.

We report allelic variation at the APOE locus in three European and four Indian populations and evaluate global patterns of genetic variation at this locus. The large, intricate and unexpected heterogeneity of this locus in its global perspective may have insightful consequences, which we have explored in this paper.

Apolipoprotein E genotypes were determined in four population groups (Punjabi Sikhs, Punjabi Hindus, Maria Gonds and Koch, total individuals = 497) of India and three regionally sub-divided British populations (Nottinghamshire, East Midlands and West Midlands, total individuals = 621). The extent and distribution of APOE allele frequencies were compared with 292 populations of the world using a variety of multivariate methods.

Three alleles, APOE*E2, APOE*E3 and APOE*E4, were observed with contrasting variation, although *E4 was absent in the tribal population of Koch. Higher heterozygosities (>43%) in British populations reflected their greater genetic diversity at this locus. The overall pattern of allelic diversity among these populations is comparable to many European and Indian populations. At a global level, higher frequencies of the *E2 allele were observed in Africa and Oceania (0.099 +/- 0.083 and 0.111 +/- 0.052, respectively). Similarly, *E4 allele averages were higher in Oceania (0.221 +/- 0.149) and Africa (0.209 +/- 0.090), while Indian and Asian populations showed the highest frequencies of *E3 allele. The coefficient of gene differentiation was found to be highest in South America (9.6%), although the highest genetic diversity was observed in Oceania (48.7%) and Africa (46.3%). APOE*E2 revealed a statistically significant decreasing cline towards the north in Asia (r = -0.407, d.f. = 70, p < 0.05), which is not compatible with the coronary heart disease statistics in this continent. APOE*E4 showed a significant increasing cline in North European populations. Spatial autocorrelation analysis shows that the variation at this locus is influenced by 'isolation by distance' with a strong positive correlation for lower distances up to 1313 km.

Overall APOE allelic variation in UK and Indian populations is comparable to previous studies but in tribal populations *E4 allele frequency was very low or absent. At a global level allelic variation shows that geography, isolation by distance, genetic drift and possibly pre-historical selection are responsible for shaping the spectrum of genetic variation at the APOE gene. Overall, APOE is a good anthropogenetic and clinical diagnostic marker.