A global perspective on hepatitis B-related single nucleotide polymorphisms and evolution during human migration.

Area of Science:

• Genetics
• Immunology
• Anthropology

Background:

• Genome-wide association studies link human leukocyte antigen (HLA)-DP and HLA-DQ to persistent hepatitis B virus (HBV) infection in Asia.
• Understanding the evolution of HBV-related single nucleotide polymorphisms (SNPs) and their correlation with chronic HBV infection across diverse populations is crucial.

Purpose of the Study:

• To investigate the global distribution and evolutionary patterns of HBV-related and immune-related SNPs.
• To correlate these genetic variations with chronic HBV infection and human migration.

Main Methods:

• Downloaded worldwide SNP data from 26 populations via the 1,000 Genomes Project.
• Analyzed 12 HBV-related SNPs on the HLA locus, 2 HBV immune-related SNPs, 3 hepatitis C virus immune-related SNPs, and 5 control SNPs.
• Compared allele frequencies across continents and identified significant shifts between populations.

Main Results:

• Significant differences in allele frequencies for most HBV- and HLA-related SNPs were observed in East Asia compared to other continents.
• A sharp allele frequency change in 8 of 12 SNPs was noted between Bengali and Dai populations at the South-East Asia junction.
• Immune-related SNPs showed significant shifts after migration out of Africa, with a trend towards lower expression genotypes.

Conclusions:

• Two stages of genetic adaptation toward a weaker immune response occurred during human migration out of Africa.
• These adaptations may represent a survival strategy to mitigate cytokine storms and adapt to new environments.
• The genetic basis of chronic HBV infection in Africa requires further investigation due to the absence of typical HBV-related SNP genotypes found elsewhere.