Reyes-Reyes Elizabeth, Herrera-Isidrón José Alfredo, Cuétara-Lugo Elizabeth, Shkedy Zhiv, Valkenborg Dirk, Pérez-Novo Claudina Angela, Fernández-Peña Gisselle, González-Pérez Idania, Fernández-Pérez Miguel David, Vanden-Berghe Wim, Rodeiro-Guerra Idania
Laboratory of Clinical Experimental Pharmacology, Teaching and Research Department, Institute of Oncology and Radiobiology (INOR), Havana, Cuba.
Laboratory of Pharmacology, Department of Pharmacology, Institute of Marine Sciences (ICIMAR), Havana, Cuba.
Front Pharmacol. 2024 Sep 27;15:1467036. doi: 10.3389/fphar.2024.1467036. eCollection 2024.
The Cuban population is genetically diverse, and information on the prevalence of genetic variants is still limited. As complex admixture processes have occurred, we hypothesized that the frequency of pharmacogenetic variants and drug responses may vary within the country. The aims of the study were to describe the frequency distribution of 43 single-nucleotide variants (SNVs) from 25 genes of pharmacogenetic interest within the Cuba population and in relation to other populations, while taking into consideration some descriptive variables such as place of birth and skin color.
SNVs were analyzed in 357 unrelated healthy Cuban volunteers. Genotype, allele frequencies, and ancestry proportions were determined, and the pairwise fixation index (F ) was evaluated.
Hardy-Weinberg equilibrium (HWE) deviations in six loci (rs11572103, rs2740574, rs776746, rs3025039, rs861539, and rs1762429) were identified. Minor allele frequencies (MAFs) ranged from 0.00 to 0.15 for variants in genes encoding xenobiotic metabolizing enzymes. They also ranged from 0.01 to 0.21 for variants in DNA repair, growth factors, methyltransferase, and methyl-binding proteins, while they ranged from 0.04 to 0.27 for variants in the O-6-methylguanine-DNA methyltransferase enzyme. Moderate genetic divergence was observed upon comparison to Africans (F = 0.071 and SD 0.079), with 19 markers exhibiting moderate-to-large genetic differentiation. The average European, African, and Amerindian ancestry proportions were 67.8%, 27.2%, and 5.3%, respectively. Ancestry proportions differed by skin color and birthplace for both African and European components, with the exception of the European component, which showed no significant difference between individuals from Western and Eastern regions. Meanwhile, the statistical significance varied in comparisons by skin color and birthplace within the Amerindian component. Low genetic divergence was observed across geographical regions. We identified 12 variants showing moderate-to-large differentiation between White/Black individuals.
Altogether, our results may support national strategies for the introduction of pharmacogenetic tools in clinical practice, contributing to the development of precision medicine in Cuba.
古巴人口在基因上具有多样性，关于基因变异流行情况的信息仍然有限。由于发生了复杂的混合过程，我们推测药物遗传学变异的频率和药物反应在该国可能存在差异。本研究的目的是描述古巴人群中25个药物遗传学相关基因的43个单核苷酸变异（SNV）的频率分布，并与其他人群进行比较，同时考虑一些描述性变量，如出生地和肤色。
对357名无亲缘关系的健康古巴志愿者的SNV进行分析。确定基因型、等位基因频率和祖先比例，并评估成对固定指数（F）。
在六个位点（rs11572103、rs2740574、rs776746、rs3025039、rs861539和rs1762429）发现了哈迪-温伯格平衡（HWE）偏差。编码外源性代谢酶基因变异的次要等位基因频率（MAF）范围为0.00至0.15。DNA修复、生长因子、甲基转移酶和甲基结合蛋白基因变异的MAF范围为0.01至0.21，而O-6-甲基鸟嘌呤-DNA甲基转移酶基因变异的MAF范围为0.04至0.27。与非洲人相比，观察到中等程度的遗传分化（F = 0.071，标准差0.079），19个标记表现出中等至较大的遗传差异。欧洲、非洲和美洲印第安人的平均祖先比例分别为67.8%、27.2%和5.3%。非洲和欧洲成分的祖先比例因肤色和出生地而异，但欧洲成分除外，西部地区和东部地区的个体之间没有显著差异。同时，美洲印第安人成分中按肤色和出生地进行比较时，统计学意义有所不同。不同地理区域之间观察到低水平的遗传分化。我们鉴定出12个在白种人/黑种人个体之间表现出中等至较大差异的变异。
总体而言，我们的结果可能支持在临床实践中引入药物遗传学工具的国家战略，为古巴精准医学的发展做出贡献。
