Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, Universidad Nacional Autónoma de México-UNAM-Instituto Nacional de Medicina Genómica-INMEGEN, Mexico City, Mexico.
PLoS One. 2013 Aug 8;8(8):e70640. doi: 10.1371/journal.pone.0070640. eCollection 2013.
Several studies have identified multiple obesity-associated loci mainly in European populations. However, their contribution to obesity in other ethnicities such as Mexicans is largely unknown. The aim of this study was to examine 26 obesity-associated single-nucleotide polymorphisms (SNP) in a sample of Mexican mestizos.
9 SNPs in biological candidate genes showing replications (PPARG, ADRB3, ADRB2, LEPR, GNB3, UCP3, ADIPOQ, UCP2, and NR3C1), and 17 SNPs in or near genes associated with obesity in first, second and third wave GWAS (INSIG2, FTO, MC4R, TMEM18, FAIM2/BCDIN3, BDNF, SH2B1, GNPDA2, NEGR1, KCTD15, SEC16B/RASAL2, NPC1, SFRF10/ETV5, MAF, PRL, MTCH2, and PTER) were genotyped in 1,156 unrelated Mexican-Mestizos including 683 cases (441 obese class I/II and 242 obese class III) and 473 normal-weight controls. In a second stage we selected 12 of the SNPs showing nominal associations with obesity, to seek associations with quantitative obesity-related traits in 3 cohorts including 1,218 Mexican Mestizo children, 945 Mexican Mestizo adults, and 543 Indigenous Mexican adults.
After adjusting for age, sex and admixture, significant associations with obesity were found for 6 genes in the case-control study (ADIPOQ, FTO, TMEM18, INSIG2, FAIM2/BCDIN3 and BDNF). In addition, SH2B1 was associated only with class I/II obesity and MC4R only with class III obesity. SNPs located at or near FAIM2/BCDIN3, TMEM18, INSIG2, GNPDA2 and SEC16B/RASAL2 were significantly associated with BMI and/or WC in the combined analysis of Mexican-mestizo children and adults, and FTO locus was significantly associated with increased BMI in Indigenous Mexican populations.
Our findings replicate the association of 8 obesity-related SNPs with obesity risk in Mexican adults, and confirm the role of some of these SNPs in BMI in Mexican adults and children.
多项研究已在欧洲人群中发现了多个与肥胖相关的基因座。然而，它们对其他族群（如墨西哥人）肥胖的影响在很大程度上尚不清楚。本研究旨在检测墨西哥裔混血儿样本中 26 个与肥胖相关的单核苷酸多态性（SNP）。
在本研究中，对生物候选基因中显示出可复制性的 9 个 SNP（PPARG、ADRB3、ADRB2、LEPR、GNB3、UCP3、ADIPOQ、UCP2 和 NR3C1），以及与第一、二、三波 GWAS 中肥胖相关的基因内或附近的 17 个 SNP（INSIG2、FTO、MC4R、TMEM18、FAIM2/BCDIN3、BDNF、SH2B1、GNPDA2、NEGR1、KCTD15、SEC16B/RASAL2、NPC1、SFRF10/ETV5、MAF、PRL、MTCH2 和 PTER）进行了基因分型。共纳入了 1156 名无亲缘关系的墨西哥裔混血儿，包括 683 例病例（441 例肥胖 I/II 级和 242 例肥胖 III 级）和 473 例正常体重对照。在第二阶段，我们选择了 12 个与肥胖有显著关联的 SNP，以在包括 1218 名墨西哥裔混血儿儿童、945 名墨西哥裔混血儿成人和 543 名土著墨西哥成人在内的 3 个队列中，寻找与肥胖相关的定量特征的关联。
在病例对照研究中，调整年龄、性别和混合因素后，发现 6 个基因与肥胖显著相关（ADIPOQ、FTO、TMEM18、INSIG2、FAIM2/BCDIN3 和 BDNF）。此外，SH2B1 仅与 I/II 级肥胖相关，MC4R 仅与 III 级肥胖相关。在对墨西哥裔混血儿儿童和成人的联合分析中，位于 FAIM2/BCDIN3、TMEM18、INSIG2、GNPDA2 和 SEC16B/RASAL2 或附近的 SNP 与 BMI 和/或 WC 显著相关，而 FTO 基因座与土著墨西哥人群 BMI 的增加显著相关。
我们的研究结果复制了 8 个与肥胖相关的 SNP 与墨西哥成年人肥胖风险的关联，并证实了这些 SNP 中的一些在墨西哥成年人和儿童 BMI 中的作用。
