The Study On The Relationship Between APOBEC3B Gene Deletion And The Alu Insertion Of ACE Gene

Insertion/deletion (I/D) polymorphism is an important type of genetic marker.APOBEC3B belongs to the cytidine deaminase family of APOBEC3. It hasantiretroviral activity because of its ability of converting cytosine to uracil.APOBEC3B is also an inhibitor of retrotransposons, especially it can powerfullysuppress the retrotransposition of Alu which is a kind of short interspersed element.Genetic research has discovered a common29.5kb gene deletion polymorphism onthe chromosome22. The deletion removes the entire APOBEC3B coding region andresults in no expression of the protein. APOBEC3B deletion frequency changessignificantly in diverse ethnic populations across the world, and its change trend justfits the out-of-Africa expansion route of humanity.Alu elements, which are approximately300bp long retrotransposons specific tomammals, emerged about65million years ago and have been amplified throughlong time retrotransposition to reach the present number of more than one millioncopies, occupying about10%of the whole human genome. High density of copies islocated inside the introns in particular. Therefore, Alu elements are regarded as themost successful transposable elements. Angiotensin converting enzyme (ACE) is akey enzyme of the renin–angiotensin system (RAS). The enzyme plays its vital rolein the regulation of blood pressure and water/sodium metabolism of human body byconverting the inactive Angiotensin I to the vasoconstrictor Angiotensin II. HumanACE gene is located on the chromosome17, and an insertion/deletion polymorphismis characterized by the presence (insertion) or absence (deletion) of an Alu elementinside the intron16. Interestingly, the deletion was found to be associated withhigher ACE expression level. The Alu I/D polymorphism of ACE gene has alwaysbeen the research hotspot of genomics. According to the researches, it is related with many diseases and has also been suggested to affect human adaptability to climatechanges during the out-of-Africa expansion. Coincidentally, its distribution alsoshows high variability among populations from different geographic regions.Furthermore, its variation trend coincides with the out-of-Africa expansion route justlike APOBEC3B I/D polymorphism.It is very interesting that the I/D polymorphism of APOBEC3B, a powerful Aluretrotransposition inhibitor, shares the similar variation trend of global distributionwith the Alu I/D polymorphism of ACE gene. Then, does any correlation existbetween them? To explore this problem, we adopted research methods as below:1) Calculating and comparing the concrete distributions of APOBEC3B I/Dpolymorphism and the Alu I/D polymorphism of ACE gene in different geographicregions based on the data of published reports.2)2780unrelated persons were selected by a simple random sampling approachfrom Jilin Province and genotyped for APOBEC3B I/D polymorphism and the AluI/D polymorphism of ACE gene. The genotype/allele distributions of the two I/Dpolymorphisms and their combination in the sample population were counted andanalyzed with statistical methods.3) A subgroup of1199adults was measured for some important clinicalcharacteristics. The1199adults were grouped according to their genotypes of thetwo I/D polymorphisms and the clinical characteristics were compared betweendifferent groups with statistical methods.The research results were as below:1) The global geographic distributions of APOBEC3B I/D polymorphism andthe Alu I/D polymorphism of ACE gene display opposite variation trends to eachother. The frequency of APOBEC3B deletion exhibits an obvious rising trend alongthe out-of-Africa expansion route, while the frequency of ACE Alu insertionincreases gradually following the route. Even more amazing is that the frequenciesof APOBEC3B deletion and ACE Alu insertion were observed to rise almost parallelalong the route. 2) The distributions of the two I/D polymorphisms among the samplepopulation were close to the previous reports about Chinese. But a significantdifference was discovered between ACE genotype/allele distribution in A3B DDgroup and that in A3B II/ID group (P=0.045and0.015, respectively). The Aluinsertion frequency of ACE gene in the former group was significantly highercompared to the latter group.3) No evident effects on the clinical characteristics were found for theinteraction between the two I/D polymorphisms.On the basis of our results and previous reports, we present an opinion tointerpret the relationship between APOBEC3B I/D polymorphism and the Alu I/Dpolymorphism of ACE gene. It is that ACE Alu insertion was probably an inducedfollow-up event of A3B deletion before or during the early stage of the out-of-Africaexpansion. The occurrence of APOBEC3B deletion event has great meaning for thehistory of modern humanity, because the Alu insertion of ACE gene greatlypromoted human adaptability and survival rate when suffering climate changesduring the out-of-Africa expansion. Besides, APOBEC3B deletion may has alsocaused the occurrence of other Alu insertion events. Further researches are worthy ofbeing done in the future to explore the relationship between A3B deletion and ACEAlu insertion or other Alu insertions.