盐诱导激酶3基因单核苷酸多态性rs12225230与儿童肥胖表型的关联

  目的  探讨盐诱导激酶3(SIK3)基因单核苷酸多态性rs12225230与儿童青少年肥胖相关表型的关联，为儿童青少年肥胖的筛查干预提供证据。  方法  整群抽取北京市2 030名7~18岁儿童青少年为研究对象，进行身体测量及超重肥胖分组。利用基质辅助激光解析/电离飞行时间质谱(MALDI-TOF MS)检测单核苷酸多态性rs12225230基因型频率。分别采用Logistic回归和多元线性回归分析单核苷酸多态性rs12225230与肥胖、中心性肥胖相关表型的关联。使用Polyphen2数据库分析单核苷酸多态性rs12225230对SIK3基因蛋白质功能的影响；使用GTEx数据库探索与单核苷酸多态性rs12225230相关联的组织特异性基因表达。  结果  单核苷酸多态性rs12225230 C等位基因是儿童青少年肥胖、重度肥胖发生的危险因素(OR_肥胖=1.50，95%CI=1.10~2.04，P=0.01；OR_重度肥胖=1.72，95%CI=1.23~2.39，P < 0.01)。单核苷酸多态性rs12225230 C等位基因与腰围、腰高比存在正相关(β_腰围=1.40，95%CI=0.28~2.52，P=0.01；β_腰高比=0.01，95%CI=0.00~0.02，P=0.01)；单核苷酸多态性rs12225230 C等位基因对SIK3基因编码的蛋白质可能存在功能损害，且与心脏组织中APOA1基因表达升高相关。  结论  SIK3基因单核苷酸多态性rs12225230与儿童青少年肥胖、中心性肥胖相关，且与APOA1表达相关，但与脂代谢之间的关联尚需进一步论证。

Association between SIK3 SNP rs12225230 with obese phenotype in children

  Objective  To assess the associations between the single-nucleotide polymorphism (SNP) rs12225230 of salt inducible kinase 3 (SIK3) and obesity/central obesity in children, and to provide evidence for screening intervention for obesity in children and adolescents.  Methods  A cluster sampling of 2 030 children aged 7-18 years in Beijing were enrolled and height, weight and waist circumference were measured according to the manufacturer. The genotype frequency of SNP rs12225230 was detected by matrix-assisted laser analysis/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Logistic regression and multiple linear regression were applied to analyze the associations between SNP rs12225230 and overweight/obesity and central obesity. Polyphen2 database was used to predict the effect of SNP rs12225230 on the protein function of SIK3. GTEx database was used to explore expression quantitative trait loci (eQTL) of SNP rs12225230.  Results  C allele of SNP rs12225230 was a risk allele for obesity and severe obesity in children (OR_obesity=1.50, 95%CI=1.10-2.04, P=0.01; OR_{severe obesity}=1.72, 95%CI=1.23-2.39, P < 0.01). The SNP rs12225230 was positively associated with waist circumference and waist height ratio (β_{waist circumference}=1.40, 95%CI=0.28-2.52, P=0.01; β_{waist height ratio}=0.01, 95%CI=0.00-0.02, P=0.01). C allele of SNP rs12225230 may be harmful to the function of the protein encoded by the SIK3, and was positively related to the expression of the APOA1 in the heart tissue.  Conclusion  SNP rs12225230 is associated with obesity and central obesity in children, and SNP rs12225230 may affect the expression of the APOA1 in children, but its association with lipid metabolism needs to be verified.