Department of Pediatrics, Seconda Università degli Studi di Napoli, Napoli, Italy.
PLoS One. 2011;6(11):e27933. doi: 10.1371/journal.pone.0027933. Epub 2011 Nov 28.
A polymorphism in adiponutrin/patatin-like phospholipase-3 gene (PNPLA3), rs738409 C->G, encoding for the I148M variant, is the strongest genetic determinant of liver fat and ALT levels in adulthood and childhood obesity. Aims of this study were i) to analyse in a large group of obese children the role of the interaction of not-genetic factors such as BMI, waist circumference (W/Hr) and insulin resistance (HOMA-IR) in exposing the association between the I148M polymorphism and ALT levels and ii) to stratify the individual risk of these children to have liver injury on the basis of this gene-environment interaction.
1048 Italian obese children were investigated. Anthropometric, clinical and metabolic data were collected and the PNPLA3 I148M variant genotyped.
Children carrying the 148M allele showed higher ALT and AST levels (p = 0.000006 and p = 0.0002, respectively). Relationships between BMI-SDS, HOMA-IR and W/Hr with ALT were analysed in function of the different PNPLA3 genotypes. Children 148M homozygous showed a stronger correlation between ALT and W/Hr than those carrying the other genotypes (p: 0.0045) and, therefore, 148M homozygotes with high extent of abdominal fat (W/Hr above 0.62) had the highest OR (4.9, 95% C. I. 3.2-7.8, p = 0.00001) to develop pathologic ALT.
We have i) showed for the first time that the magnitude of the association of PNPLA3 with liver enzymes is driven by the size of abdominal fat and ii) stratified the individual risk to develop liver damage on the basis of the interaction between the PNPLA3 genotype and abdominal fat.
脂肪甘油三酯脂肪酶/马铃薯球蛋白样磷脂酶 3 基因（PNPLA3）中的一个多态性 rs738409 C->G，编码 I148M 变体，是成人和儿童肥胖中肝脏脂肪和丙氨酸氨基转移酶（ALT）水平的最强遗传决定因素。本研究的目的是：i）在一大群肥胖儿童中分析非遗传因素（如 BMI、腰围（W/Hr）和胰岛素抵抗（HOMA-IR））的相互作用，以揭示 I148M 多态性与 ALT 水平之间的关联；ii）根据这种基因-环境相互作用，对这些儿童发生肝损伤的个体风险进行分层。
研究了 1048 名意大利肥胖儿童。收集了人体测量、临床和代谢数据，并对 PNPLA3 I148M 变体进行了基因分型。
携带 148M 等位基因的儿童 ALT 和 AST 水平更高（p=0.000006 和 p=0.0002，分别）。分析了不同 PNPLA3 基因型下 BMI-SDS、HOMA-IR 和 W/Hr 与 ALT 之间的关系。148M 纯合子儿童与其他基因型相比，ALT 与 W/Hr 之间的相关性更强（p：0.0045），因此，腹部脂肪程度较高（W/Hr 高于 0.62）的 148M 纯合子儿童发生异常 ALT 的最高比值比（OR）为 4.9（95%置信区间为 3.2-7.8，p=0.00001）。
我们首次表明，PNPLA3 与肝酶的关联程度取决于腹部脂肪的大小；并且根据 PNPLA3 基因型和腹部脂肪之间的相互作用，对个体发生肝损伤的风险进行分层。
