ABSTRACT
OBJECTIVE: The variant allele of rs3798220 in the apolipoprotein(a) gene (LPA) is used to assess the risk for coronary artery disease (CAD) in Europeans, where it is associated with short alleles of the Kringle IV-2 (KIV-2) copy number variation (CNV) and high lipoprotein(a) (Lp(a)) concentrations. No association of rs3798220 with CAD was detected in a GWAS of East Asians. Our study investigated the association of rs3798220 with Lp(a) concentrations and KIV-2 CNV size in non-European populations to explain the missing association of the variant with CAD in Asians. METHODS: We screened three populations from Africa and seven from Asia by TaqMan Assay for rs3798220 and determined KIV-2 CNV sizes of LPA alleles by pulsed-field gel electrophoresis (PFGE). Additionally, CAD cases from India were analysed. To investigate the phylogenetic origin of rs3798220, 40 LPA alleles from Chinese individuals were separated by PFGE and haplotyped for further SNPs. RESULTS: The variant was not found in Africans. Allele frequencies in East and Southeast Asians ranged from 2.9% to 11.6%, and were very low (0.15%) in CAD cases and controls from India. The variant was neither associated with short KIV-2 CNV alleles nor elevated Lp(a) concentrations in Asians. CONCLUSION: Our study shows that rs3798220 is no marker for short KIV-2 CNV alleles and high Lp(a) in East and Southeast Asians, although the haplotype background is shared with Europeans. It appears unlikely that this SNP confers atherogenic potential on its own. Furthermore, this SNP does not explain Lp(a) attributed risk for CAD in Asian Indians.
Subject(s)
Apolipoproteins A/genetics , DNA Copy Number Variations , Polymorphism, Single Nucleotide , Africa , Alleles , Asia , Asian People , China , Coronary Artery Disease/ethnology , Coronary Artery Disease/genetics , Electrophoresis, Gel, Pulsed-Field , Gene Frequency , Genetic Markers , Genetic Variation , Genome-Wide Association Study , Genotype , Haplotypes , Humans , India , Phylogeny , Protein Isoforms/geneticsABSTRACT
The human settlement of the Pacific Islands represents one of the most recent major migration events of mankind. Polynesians originated in Asia according to linguistic evidence or in Melanesia according to archaeological evidence. To shed light on the genetic origins of Polynesians, we investigated over 400 Polynesians from 8 island groups, in comparison with over 900 individuals from potential parental populations of Melanesia, Southeast and East Asia, and Australia, by means of Y chromosome (NRY) and mitochondrial DNA (mtDNA) markers. Overall, we classified 94.1% of Polynesian Y chromosomes and 99.8% of Polynesian mtDNAs as of either Melanesian (NRY-DNA: 65.8%, mtDNA: 6%) or Asian (NRY-DNA: 28.3%, mtDNA: 93.8%) origin, suggesting a dual genetic origin of Polynesians in agreement with the "Slow Boat" hypothesis. Our data suggest a pronounced admixture bias in Polynesians toward more Melanesian men than women, perhaps as a result of matrilocal residence in the ancestral Polynesian society. Although dating methods are consistent with somewhat similar entries of NRY/mtDNA haplogroups into Polynesia, haplotype sharing suggests an earlier appearance of Melanesian haplogroups than those from Asia. Surprisingly, we identified gradients in the frequency distribution of some NRY/mtDNA haplogroups across Polynesia and a gradual west-to-east decrease of overall NRY/mtDNA diversity, not only providing evidence for a west-to-east direction of Polynesian settlements but also suggesting that Pacific voyaging was regular rather than haphazard. We also demonstrate that Fiji played a pivotal role in the history of Polynesia: humans probably first migrated to Fiji, and subsequent settlement of Polynesia probably came from Fiji.
