AUTHOR=Zmorzynski Szymon , Szudy-Szczyrek Aneta , Popek-Marciniec Sylwia , Korszen-Pilecka Iwona , Wojcierowska-Litwin Magdalena , Luterek Małgorzata , Chocholska Sylwia , Styk Wojciech , Swiderska-Kołacz Grazyna , Januszewska Joanna , Mielnik Michal , Hus Marek , Filip Agata A. 

TITLE=ACE Insertion/Deletion Polymorphism (rs4646994) Is Associated With the Increased Risk of Multiple Myeloma

JOURNAL=Frontiers in Oncology

VOLUME=9

YEAR=2019

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2019.00044

DOI=10.3389/fonc.2019.00044

ISSN=2234-943X

ABSTRACT=<p><bold>Introduction:</bold> The insertion (I allele) deletion (D allele) polymorphism of <italic>ACE</italic> gene (rs4646994) may influence the etiopathogenesis of multiple myeloma (MM). <italic>ACE</italic> gene is expressed in bone marrow cells and encodes angiotensin converting enzyme (ACE). It converts angiotensin I to active peptide angiotensin II, which stimulates proliferation of hematopoietic stem cells. This suggests possible association of <italic>ACE</italic> I/D gene polymorphism with MM. The aim of our study was to check possible impact of this polymorphism on risk of development and outcome of MM, as well as, sensitivity to bortezomib in cell cultures derived from MM patients.</p><p><bold>Objects and Methods:</bold> Genomic DNA from 98 newly diagnosed MM patients and 100 healthy blood donors were analyzed by PCR method. Chromosomal aberrations were detected by use of cIg-FISH. In a subgroup of 40 MM patients nucleated bone marrow cells were treated with bortezomib <italic>in vitro</italic>.</p><p><bold>Results:</bold> The Hardy-Weinberg equilibrium test showed that genotypic frequencies diverged significantly from the equilibrium. The differences between I and D allele frequencies in control and study population were significant (<italic>p</italic> = 0.046). We observed the association between DD genotype and more than 2-fold risk of MM - OR = 2.69; <italic>p</italic> &lt; 0.0001. We did not detect any significant differences among studied genotypes regarding clinical and laboratory parameters. Moreover, we did not observe the association between survival of MM patients and I/D genotypes. Bortezomib increased number of apoptotic and necrotic cells, but the only statistically significant differences were observed in the number of viable cells at 1 nM between ID and DD genotypes (<italic>p</italic> = 0.026).</p><p><bold>Conclusion:</bold> Presented results confirmed the significant relationship between <italic>ACE</italic> (I/D) polymorphism and risk of MM development. We did not observe the association of <italic>ACE</italic> I/D polymorphism with disease outcome and bortezomib <italic>in vitro</italic> sensitivity.</p>