Positive correlation of cg16672562 methylation with obesity-related traits in childhood obesity, and its independence with underlying HIF3A (hypoxia-inducible factor 3a) genetic background
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Suman Lee1, Hyo Jin Kim2, Sohee Han1, Jae-Pil Jeon1, Sang-Ick Park2, Ho-Yeong Yu1, Mi Yeong Hwang1 and Juyoung Lee1
1Center for Genome Science, National Institute of Health, Chungju, Chungcheongbuk-do, 361-951, Republic of Korea
2Center for Biomedical Sciences, National Institute of Health, Chungju, Chungcheongbuk-do, 361-951, Republic of Korea
Suman Lee, email: firstname.lastname@example.org
Keywords: cg16672562, HIF3A, obesity, CpG methylation, cis-meQTL
Received: January 16, 2017 Accepted: May 27, 2017 Published: June 27, 2017
Differential methylations of the HIF3A (hypoxia-inducible factor 3a) gene have been linked to body mass index (BMI). To explore the association of these methylations to childhood obesity, we measured 5 CpG methylation sites (cg27146050, cg46801562, cg22891070, cg16672562 and cg46801675) in intron 1 of the HIF3A gene by pyrosequencing, in the Korean population (mean age: 13.9 yrs, 305 obese cases and 387 controls). Two CpG methylations, cg46801562 and cg16672562, had statistically significant association with childhood obesity (P = 2.09E-9 and 1.66E-7, respectively). Notably, in the case of cg16672562, all correlations were significantly positive with BMI (beta = 0.285, P = 1.652E-13), waist-hip ratio (beta = 0.0028, P = 1.42E-15) and fasting plasma glucose level (beta = 0.0645, P = 2.61E-4), when analyzed by linear regression, with age and sex as covariates. We investigated any genetic effect of cg16672562 methylation by using 14 single nucleotide polymorphisms (SNP) identified by exome sequencing of the HIF3A locus. cg16672562 methylation showed no statistically significant changes due to the 14 polymorphisms. In this study, we show that cg16672562 is the most significant blood DNA methylation marker for childhood obesity in the Korean population, and might be independent of any underlying HIF3A genetic background.
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