Marrachelli Vannina G, Monleon Daniel, Rentero Pilar, Mansego María L, Morales Jose Manuel, Galan Inma, Segura Remedios, Martinez Fernando, Martin-Escudero Juan Carlos, Briongos Laisa, Marin Pablo, Lliso Gloria, Chaves Felipe Javier, Redon Josep
Metabolomic and Molecular Image Lab, Health Research Institute, INCLIVA, Valencia, Spain.
Genotyping and Genetic Diagnosis Unit, Health Research Institute, INCLIVA, Valencia, Spain.
PLoS One. 2014 Jun 11;9(2):e98227. doi: 10.1371/journal.pone.0098227. eCollection 2014.
To identify factors related with the risk to develop microalbuminuria using combined genomic and metabolomic values from a general population study. One thousand five hundred and two subjects, Caucasian, more than 18 years, representative of the general population, were included. Blood pressure measurement and albumin/creatinine ratio were measured in a urine sample. Using SNPlex, 1251 SNPs potentially associated to urinary albumin excretion (UAE) were analyzed. Serum metabolomic profile was assessed by 1H NMR spectra using a Brucker Advance DRX 600 spectrometer. From the total population, 1217 (mean age 54 ± 19, 50.6% men, ACR>30 mg/g in 81 subjects) with high genotyping call rate were analysed. A characteristic metabolomic profile, which included products from mitochondrial and extra mitochondrial metabolism as well as branched amino acids and their derivative signals, were observed in microalbuminuric as compare to normoalbuminuric subjects. The comparison of the metabolomic profile between subjects with different UAE status for each of the genotypes associated to microalbuminuria revealed two SNPs, the rs10492025_TT of RPH3A gene and the rs4359_CC of ACE gene, with minimal or no statistically significant differences. Subjects with and without microalbuminuria, who shared the same genotype and metabolomic profile, differed in age. Microalbuminurics with the CC genotype of the rs4359 polymorphism and with the TT genotype of the rs10492025 polymorphism were seven years older and seventeen years younger, respectively as compared to the whole microalbuminuric subjects. With the same metabolomic environment, characteristic of subjects with microalbuminuria, the TT genotype of the rs10492025 polymorphism seems to increase and the CC genotype of the rs4359 polymorphism seems to reduce risk to develop microalbuminuria.
利用一项普通人群研究中的基因组和代谢组学综合数据,确定与发生微量白蛋白尿风险相关的因素。纳入了1502名年龄超过18岁的白种人受试者,他们具有普通人群的代表性。测量了血压,并检测了尿样中的白蛋白/肌酐比值。使用SNPlex分析了1251个可能与尿白蛋白排泄(UAE)相关的单核苷酸多态性(SNP)。使用布鲁克Advance DRX 600光谱仪通过1H NMR光谱评估血清代谢组学特征。在总共1217名(平均年龄54±19岁,男性占50.6%,81名受试者的ACR>30mg/g)基因分型检出率高的人群中进行了分析。与正常白蛋白尿受试者相比,在微量白蛋白尿受试者中观察到一种特征性的代谢组学特征,其中包括线粒体和线粒体外代谢产物以及支链氨基酸及其衍生信号。对于与微量白蛋白尿相关的每种基因型,比较不同UAE状态受试者之间的代谢组学特征,发现两个SNP,即RPH3A基因的rs10492025_TT和ACE基因的rs4359_CC,差异极小或无统计学意义。具有相同基因型和代谢组学特征但有无微量白蛋白尿的受试者在年龄上存在差异。与整个微量白蛋白尿受试者相比,rs4359多态性的CC基因型和rs10492025多态性的TT基因型的微量白蛋白尿受试者分别年长7岁和年轻17岁。在具有微量白蛋白尿受试者特征的相同代谢组学环境下,rs10492025多态性的TT基因型似乎会增加发生微量白蛋白尿的风险,而rs4359多态性的CC基因型似乎会降低这种风险。