SNP 1799930 的变异确定了超重和肥胖症患者体内异生物高代谢的保护特性

M. Pinhel, L. Watanabe, N. Noronha, G. Rodrigues, F. Barbosa Junior, Carolina Nicoletti, C. Nonino
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摘要

:背景和目的:乙酰化能力所涉及的酶会影响多种异生物体的代谢,这些异生物体会沉积在脂肪组织中,阻碍体重减轻,从而导致肥胖。我们的目的是鉴定与异生物代谢相关的单核苷酸多态性(SNPs),并将其与体重超标者血清中的重金属水平联系起来。研究方法样本选自巴西圣保罗大学 Ribeir ã o Preto 医学院。对 23 个 SNPs 进行了基因分型阵列分析。使用软件包 "snpReady"(CRAN)和 "imput"(Bioconductor)中的函数进行质量控制和估算。研究结果本研究选取了 189 名男女混血儿,平均年龄为 42.2 ± 12.9 岁,平均体重指数为 45.1 ± 11.4 kg/cm 2。在 23 个被评估的 SNP 群中,我们观察到 NAT2 基因(N-乙酰特拉弗酶)中 SNP 1799930 的频率较高。基因型与不同金属的血清水平相关。我们观察到,与代谢缓慢的个体(GG)(64.0 ± 37.2 µ g/L;p = 0.02)相比,突变等位基因的同源个体(AA)(即快速代谢者)的铝(Al)含量(51.4 ± 18.9 µ g/L)较低。与杂合子(AG)相比,没有观察到差异。此外,快代谢者的体重指数(48.7 ± 12.8 kg/cm 2)高于慢代谢者(45.9 ± 10.4 kg/cm 2;p < 0.05)。讨论快速代谢者似乎只有在同卵双生(即剂量依赖性基因)的情况下才有更大的 Al 代谢能力,才能发挥其作用。有趣的是,AA 基因型的存在与较高的体重指数有关,这表明应开展更大规模的研究,调查金属在脂肪组织中的沉积情况。
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Variant of SNP 1799930 Identifies the Protective Character of High Metabolizing of Xenobiotics in Individuals with Overweight and Obesity
: Background and Objectives: Enzymes involved with acetylation capacity affects the metabolization of several xenobiotics that can be deposited in adipose tissue and hinder weight loss, leading to obesity. Our aim was to identify single nucleotide polymorphisms (SNPs) related to the xenobiotic’s metabolism and to associate such with the serum levels of heavy metals in an individual with excess body weight. Methods: The sample was selected at the Ribeir ã o Preto Medical School at the University of S ã o Paulo, Brazil. Genotyping arrays were performed with 23 SNPs. Quality control and imputation steps were applied using the functions in the package ‘snpReady’ (CRAN) and ‘imput’ (Bioconductor). Results: This study selected 189 individuals of mixed ethnicity of both sexes, with a mean age of 42.2 ± 12.9 years and a mean BMI of 45.1 ± 11.4 kg/cm 2 . From the cluster of 23 evaluated SNPs, we observed a higher frequency of SNP 1799930 in the NAT2 gene (N-acetyltraferase). The genotypes were correlated to the serum levels of different metals. We observed that individuals homozygous for the mutant allele (AA), called fast metabolizers, had lower levels of aluminum (Al) (51.4 ± 18.9 µ g/L) compared to those considered slow metabolizers (GG) (64.0 ± 37.2 µ g/L; p = 0.02). No difference was observed when compared with heterozygosity (AG). Furthermore, the BMI of fast metabolizers (48.7 ± 12.8 kg/cm 2 ) was higher than the slow metabolizer individuals (45.9 ± 10.4 kg/cm 2 ; p < 0.05). Discussion: Fast metabolizers seem to have a greater Al metabolization only in homozygosis, that is, the dose-dependent gene, to exert its effect. Interestingly, the presence of the AA genotype is associated with a higher BMI, suggesting that larger studies should be carried out investigating the deposition of metals in adipose tissue
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