A Systematic Review of Single Nucleotide Polymorphisms Associated With Metabolic Syndrome in Children and Adolescents

Abstract

Context: Metabolic syndrome (MetS) is defined as clustering of risk factors including obesity, dyslipidemia, hyperglycemia, and hypertension, which is associated with increased risk of cardiovascular disease (CVD) and Type 2 diabetes mellitus (T2DM). Objectives: The present study aimed at reviewing all reported single-nucleotide polymorphisms (SNPs) related to childhood metabolic syndrome (MetS). Data Sources: In this review, an electronic literature search was conducted in PubMed and Huge Navigator database. For the HuGE Navigator search, we used the "metabolic syndrome" search term. For the PubMed search, we used "metabolic syndrome", "child", "adolescents", "pediatrics", "genes", and "polymorphism", without any restriction for time and language. Study Selection: Human studies with cross-sectional or case-control designs, which contained MetS as outcome and recruited participants younger than 21 years, were included. All definitions of pediatrics MetS were acceptable. Data Extraction: This study was designed as systematic review without meta-analysis in accordance with the preferred reporting item for systematic reviews meta-analysis (PRISMA) statement recommendation. After excluding duplicated and irrelevant studies, data extraction and quality control were conducted by 2 researchers using STROBE checklist. Results: In this review, during primary literature search, 219 and 1025 articles were identified through PubMed and HuGE navigator database, respectively. During 2 refining steps and after quality assessment, 38 qualified articles were evaluated at the final step. According to the whole data of systematic review results, the number of total population and points of data were 14 536. Number of studied genes and related SNP were 60 and 125, respectively. SNPs of the following genes were associated with MetS: GCK, HNFA alpha, SHBG, PON1, adiponectin, obesity related genes (FTO, MC4R, GNPDA2, BDNF, FAIM2, NPC1, SEC16B, SH2B1, PCSK1, KCTD15, and BAT2), PAI, AT1R, and SR-BI. SNPs of the following genes were associated with component of MetS: GCK, ACE, ABCA1, SREBP-1, miR-33b, PAI, IL6R, IL18, TCF7L2, ADRB2, and TNF alpha. SNPs of the following genes did not have any association with MetS or its components: CRP, APOA5, PPAR gamma, PGC-1 gamma, Tfam. Conclusions: The findings of this review revealed that most reported SNPs are related to lipid disorders mainly triglyceride and HDL and insulin resistance. It is suggested that combination effect of most of the reported SNPs or their interaction with environmental factors would be more effective for development of MetS in children.