Ramírez Viviana, Salcedo-Bellido Inmaculada, Rodrigo Lourdes, Gil Hernández Fernando, Olmedo Pablo, Martínez-González Luis Javier, Álvarez-Cubero María Jesús, Rivas Ana
Department of Nutrition and Food Science, Faculty of Pharmacy, University of Granada, Granada, Spain; GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government PTS Granada, Avenida de la Ilustración, 114, 18016 Granada, Spain; Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain.; Institute of Nutrition and Food Technology "Jose Mataix Verdú", Biomedical Research Center, University of Granada, Granada, Spain.
Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain.; Department of Preventive Medicine and Public Health, Faculty of Pharmacy, University of Granada, Granada, Spain; Consortium for Biomedical Research in Epidemiology & Public Health (CIBER en Epidemiología y Salud Pública-CIBERESP), Monforte de Lemos 5, 2809 Madrid, Spain.
Sci Total Environ. 2023 May 15;873:162333. doi: 10.1016/j.scitotenv.2023.162333. Epub 2023 Feb 20.
Exposure to metal(loid)s during critical developmental windows could result in permanent damage to the target organ system, increasing susceptibility to disease later in life. In view of the fact that metals(loid)s have been shown to work as obesogens, the aim of the present case-control study was to evaluate the modification effect of exposure to metal(loid)s on the association between SNPs in genes involved in metal(loid) detoxification and excess body weight among children. A total of 134 Spanish children aged 6-12 years old were included (88 controls and 46 cases). Seven SNPs (GSTP1 rs1695 and rs1138272; GCLM rs3789453, ATP7B rs1061472, rs732774 and rs1801243; and ABCC2 rs1885301) were genotyped on GSA microchips, and ten metal(loid)s were analysed in urine samples through Inductively coupled plasma mass spectrometry (ICP-MS). Multivariable logistic regressions were conducted to assess the genetic and metal exposures' main association and interaction effects. GSTP1 rs1695 and ATP7B rs1061472 showed significant effects on excess weight increase in those children carrying two copies of the risk G allele and being highly exposed to chromium (ORa = 5.38, p = 0.042, p interaction = 0.028 for rs1695; and ORa = 4.20, p = 0.035, p interaction = 0.012 for rs1061472) and lead (ORa = 7.18, p = 0.027, p interaction = 0.031 for rs1695, and ORa = 3.42, p = 0.062, p interaction = 0.010 for rs1061472). Conversely, GCLM rs3789453 and ATP7B rs1801243 appeared to play a protective role against excess weight in those exposed to copper (ORa = 0.20, p = 0.025, p interaction = 0.074 for rs3789453) and lead (ORa = 0.22, p = 0.092, p interaction = 0.089 for rs1801243). Our findings provide the first proof that interaction effects could exist between genetic variants within GSH and metal transporting systems and exposure to metal(loid)s, on excess body weight among Spanish children.
在关键发育窗口期接触金属（类金属）可能会导致靶器官系统受到永久性损伤，增加日后患疾病的易感性。鉴于金属（类金属）已被证明具有致肥胖作用，本病例对照研究的目的是评估接触金属（类金属）对参与金属（类金属）解毒的基因单核苷酸多态性（SNP）与儿童超重之间关联的修饰作用。共纳入134名6至12岁的西班牙儿童（88名对照和46名病例）。在基因分型芯片上对7个SNP（谷胱甘肽S-转移酶P1基因（GSTP1）的rs1695和rs1138272；谷氨酸半胱氨酸连接酶催化亚基基因（GCLM）的rs3789453，ATP7B基因的rs1061472、rs732774和rs1801243；以及ABCC2基因的rs1885301）进行基因分型，并通过电感耦合等离子体质谱法（ICP-MS）分析尿液样本中的10种金属（类金属）。进行多变量逻辑回归以评估基因和金属暴露的主要关联和交互作用。GSTP1 rs1695和ATP7B rs1061472对携带两个风险G等位基因拷贝且高暴露于铬（rs1695的调整后比值比（ORa）=5.38，p=0.042，p交互作用=0.028；rs1061472的ORa=4.20，p=0.035，p交互作用=0.012）和铅（rs1695的ORa=7.18，p=0.027，p交互作用=0.031；rs1061472的ORa=3.42，p=0.062，p交互作用=0.010）的儿童超重增加有显著影响。相反，GCLM rs3789453和ATP7B rs1801243似乎对暴露于铜（rs3789453的ORa=0.20，p=0.025，p交互作用=0.074）和铅（rs1801243的ORa=0.22，p=0.092，p交互作用=0.089）的儿童超重起到保护作用。我们的研究结果首次证明，谷胱甘肽（GSH）和金属转运系统内的基因变异与接触金属（类金属）之间可能存在交互作用，影响西班牙儿童的超重情况。
