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墨西哥梅斯蒂索2型糖尿病患者中,关于……、……、……、……、……、……和……等位基因变体的分子谱系。 (原文中部分基因名称未完整给出)

Molecular Ancestry Across Allelic Variants of , , , , , , and in Mexican-Mestizo DMT2 Patients.

作者信息

Ortega-Ayala Adiel, de la Cruz Carla González, Dorado Pedro, Rodrigues-Soares Fernanda, Castillo-Nájera Fernando, LLerena Adrián, Molina-Guarneros Juan

机构信息

Department of Pharmacology, Faculty of Medicine, National Autonomous University of Mexico, Mexico City 04510, Mexico.

Personalised Medicine and Mental Health Unit, University Institute for Bio-Sanitary Research of Extremadura (INUBE), 06080 Badajoz, Spain.

出版信息

Biomedicines. 2025 May 9;13(5):1156. doi: 10.3390/biomedicines13051156.

Abstract

: across protein-coding genes, single nucleotide allelic variants (SNVs) affect antidiabetic drug pharmacokinetics, thus contributing to interindividual variability in drug response. SNV frequencies vary across different populations. Studying ancestry proportions among SNV genotypes is particularly important for personalising diabetes mellitus type 2 (DMT2) treatment. : a sample of 249 Mexican DMT2 patients was gathered. SNVs were determined through real-time PCR (RT-PCR). Molecular ancestries were determined as 3 clusters (Native-American, European, and African) based upon 90 ancestry markers (AIMS). Statistical inference tests were performed to analyse ancestry across 23 SNV genotypes. Allele and ancestry distributions were analysed through Spearman's correlation. : ancestry medians were 65.48% Native-American (NATAM), 28.34% European (EUR), and 4.8% African (AFR). and were negatively correlated to NATAM, whereas positively to EUR. The activity score of was correlated to NATAM (Rho = 0.131, = 0.042). and the activity score of were negatively correlated to NATAM. The correlation throughout variants, such as GAT in rs72552763, was positive by EUR, while A in rs594709 was negative thereby and positive by NATAM. variant C in rs2076828 was positively correlated to NATAM. NATAM patients present higher HbA1c levels with respect to Mestizo patients ( = 0.037). Uncontrolled patients (HbA1c ≥ 7%) have a larger NATAM ancestry ( = 0.018) and lower EUR ( = 0.022) as compared to controlled patients (HbA1c < 7%). : there is a correlation between ancestry and some pharmacokinetically relevant alleles among Mexican DMT2 patients. Ethnicity is relevant for personalised medicine across different populations.

摘要

在蛋白质编码基因中,单核苷酸等位基因变异(SNV)会影响抗糖尿病药物的药代动力学,从而导致个体间药物反应的差异。SNV频率在不同人群中有所不同。研究SNV基因型中的祖先比例对于2型糖尿病(DMT2)治疗的个性化尤为重要。收集了249名墨西哥DMT2患者的样本。通过实时聚合酶链反应(RT-PCR)确定SNV。基于90个祖先标记(AIMS)将分子祖先确定为3个簇(美洲原住民、欧洲人和非洲人)。进行统计推断测试以分析23种SNV基因型的祖先。通过Spearman相关性分析等位基因和祖先分布。祖先中位数为65.48%美洲原住民(NATAM)、28.34%欧洲人(EUR)和4.8%非洲人(AFR)。[具体基因名称1]和[具体基因名称2]与NATAM呈负相关,而与EUR呈正相关。[具体基因名称3]的活性评分与NATAM相关(Rho = 0.131,P = 0.042)。[具体基因名称4]和[具体基因名称5]的活性评分与NATAM呈负相关。在整个变异中,例如rs72552763中的GAT,EUR呈正相关,而rs594709中的A则呈负相关,NATAM呈正相关。rs2076828中的变异C与NATAM呈正相关。与梅斯蒂索患者相比,NATAM患者的糖化血红蛋白(HbA1c)水平更高(P = 0.037)。与血糖控制良好的患者(HbA1c < 7%)相比,血糖控制不佳的患者(HbA1c≥7%)具有更大比例的NATAM祖先(P = 0.018)和更低比例的EUR(P = 0.022)。在墨西哥DMT2患者中,祖先与一些药代动力学相关等位基因之间存在相关性。种族对于不同人群的个性化医疗具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb4b/12109360/ac8f15e3ab9b/biomedicines-13-01156-g001.jpg

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