An obesity genetic risk score is associated with metabolic syndrome in Chinese children
Introduction
Metabolic syndrome (MetS) is characterized by a cluster of factors, including central obesity, hypertension, hypertriglyceridemia, decreased plasma high-density lipoprotein cholesterol, and elevated glucose (Bruce and Hanson, 2010). Since MetS predicts risk of type 2 diabetes (T2D) and cardiovascular diseases, it is important to clarify the causal risk factors to prevent and control for MetS. Epidemiological studies have reported that environmental factors such as high-fat food intake and lack of physical activity contribute to the development of MetS. However, genetic factors also play important roles in the pathogenesis of MetS.
Recently, several genome-wide association studies (GWASs) identified many single nucleotide polymorphisms (SNPs) associated with higher body mass index (BMI) or increased risk of obesity (Benzinou et al., 2008, Berndt et al., 2013, Frayling et al., 2007, Loos et al., 2008, Meyre et al., 2009, Speliotes et al., 2010, Thorleifsson et al., 2009, Willer et al., 2009) in populations of European ancestry. In 2007, Frayling et al. (2007) initially reported that rs9939609 in fat mass- and obesity- associated (FTO) gene was significantly associated with increased risk of T2D. However, the association disappeared after adjustment for BMI, suggesting that the effect of FTO on T2D was completely mediated through BMI. In other words, FTO is identified as the first obesity related loci. Then, the second one is Melanocortin-4 Receptor (MC4R) gene (Loos et al., 2008). The most recent loci include SNPs in/near GNPDA2, BDNF, FAIM2, NPC1, SEC16B, SH2B1, PCSK1, KCTD15 and BAT2 genes (Benzinou et al., 2008, Meyre et al., 2009, Speliotes et al., 2010, Thorleifsson et al., 2009 and Willer et al., 2009). In East Asians, most obesity loci identified in Europeans were replicated, and new additional loci were reported (Okada et al., 2012, Wen et al., 2012).
Since obesity is highly correlated with MetS, they may share similar genetic background. Actually, many studies have investigated the association between variants in FTO gene and risk of MetS in adult populations. However, the results have been inconsistent. Two similar meta-analyses (Wang et al., 2012, Zhou et al., 2012) demonstrated that variants in FTO gene were associated with increased risk of MetS in adults. However, as mentioned by Zhou et al. (2012), the majority of the previous studies did not adjust for BMI. Thus, it is still unclear whether variants in FTO gene can influence MetS independently, or mediate through BMI. Moreover, no related studies have been performed in children population. Thus, based on Beijing Child and Adolescent Metabolic Syndrome (BCAMS) study, we aim to examine the associations of 11 obesity related loci with risk of MetS and the effect of BMI on the associations among Chinese children population.
Section snippets
Subjects
Subjects were recruited from the cross-sectional population-based BCAMS study (Shan et al., 2010). The survey included completion of a questionnaire, a medical examination, anthropometric measurements, and finger capillary blood tests from a representative sample of Beijing school-aged children (N = 19,593, age range 6–18 years, 50% boys) in 2004. Of them, 3518 children who participated in a 12 hour overnight fasting venous blood testing were recruited. The detailed information has been described
Results
A total of 431 MetS cases and 3046 controls were included in the present study. Sex, age, BMI, SBP, DBP, TC, TG, HDL-C, LDL-C, and FG were different between MetS and control groups (all P < 0.05, Table 1). The genotypes of 11 SNPs were in HWE in controls (all P > 0.05, data not shown).
In the model adjusted for age and sex, GNPDA2 rs10938397, BDNF rs6265, and FAIM2 rs7138803 were nominally associated with risk of MetS (GNPDA2 rs10938397: OR = 1.21, 95% CI = 1.04–1.40, P = 0.016; BDNF rs6265: OR = 1.19, 95%
Discussion
To our knowledge, this is the first study investigating the association of 11 obesity related loci with risk of MetS among Chinese children. The results suggested that GNPDA2 rs10938397, BDNF rs6265, and FAIM2 rs7138803 were nominally associated with risk of MetS, and the SNPs in combination were significantly associated with risk of MetS. However, the associations were abolished after adjustment for BMI, suggesting that the effect of genetic loci on risk of MetS was mediated through adiposity.
Contributions
Study concept and design: JM. Acquisition of data: XZ, YS, LW, KH, DH, HC. Analysis and interpretation of data: XZ, BX. Drafting of the manuscript: XZ, BX. Critical revision of the manuscript for important intellectual content: XZ, BX, YS, LW, KH, DH, HC, XW, JM.
Conflicts of interest
The authors declare no conflict of interest.
Acknowledgements
This work was supported by the National Basic Research Program of China (973 Program, 2013CB530605), the Beijing Key Science and Technology Program (D111100000611002), the Beijing Health System Leading Talent Grant (2009-1-08), and the Research Fund for the Doctoral Program of Higher Education of China (20120131120004).
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Xiaoyuan Zhao and Bo Xi contributed equally to this work.