[Heritability of obesity in children aged 30-36 months and an analysis of single nucleotide polymorphisms at four loci in Xi'an, China].

OBJECTIVE: To study the heritability of obesity in children aged 30-36 months in Xi'an, China, as well as the role of four single nucleotide polymorphisms (SNPs) associated with body mass index in the susceptibility to obesity in children. METHODS: Random sampling was performed to select 1 637 children, aged 30-36 months, from four communities of Xi'an from March 2017 to December 2018. Physical assessment was performed for these children, and a questionnaire survey was conducted for parents. Then the Falconer regression method was used to calculate the heritability of childhood obesity. Venous blood samples were collected from 297 children who underwent biochemical examinations, among whom there were 140 children with obesity/overweight (obesity/overweight group) and 157 with normal body weight (normal body weight group). The MassARRAY RS1000 typing technique was used to detect CDKAL1 gene rs2206734, KLF9 gene rs11142387, PCSK1 gene rs261967, and GP2 gene rs12597579. The distribution of alleles and genotypes was compared between the obesity/overweight and normal body weight groups. An unconditional logistic regression model was used to investigate the benefits of dominant and recessive genetic models. RESULTS: For the 1 637 children, the heritability of obesity from the parents was 83%±8%, and the heritability from mother was slightly higher than that from father (86%±11% vs 78%±12%). There were significant differences in the distribution of rs2206734 alleles and genotypes and rs261967 genotypes between the obesity/overweight and normal body weight groups (P<0.0125). The children carrying T allele at rs2206734 had a significantly higher risk of obesity than those carrying CC (OR=0.24, P<0.0125), and the children carrying GG at rs261967 had a significantly higher risk of obesity than those carrying A allele (OR=4.11, P<0.0125). CONCLUSIONS: Genetic factors play an important role in the pathogenesis of obesity in children, and the SNPs of CDKAL1 rs2206734 and PCSK1 rs261967 are associated with the susceptibility to obesity in children aged 30-36 months in Xi'an.

Polymorphism in rs2229783 of the Alpha 1(XI) Collagen Gene Is Associated with Susceptibility to but not Severity of Kashin-Beck Disease in a Northwest Chinese Han Population.

A case-control study was conducted to investigate associations between organophosphate pesticide (OP) exposure, aggression, impulsivity, and attempted suicide. The purpose of this study was to explore whether genomic polymorphisms in the alpha 1(XI) collagen gene (COL11A1) were associated with the risk and severity of Kashin-Beck disease (KBD). Twenty-two single nucleotide polymorphisms (SNPs) in COL11A1 were genotyped in 274 KBD cases and 249 healthy controls using the Sequenom MassARRAY system. The expression of type XI collagen (COL11A) in the knee articular cartilage of 22 KBD patients and 21 controls was analyzed by immunohistochemistry. Our results showed that the frequency distribution of genotypes of the rs2229783 polymorphism in COL11A1 was significantly different between the KBD and control groups (P = 0.0003). Moreover, the expression level of COL11A in cartilage was significantly lower in the KBD group than in the controls (t = 2.637, P = 0.02). However, no association was found between the rs2229783 and the severity of KBD, suggesting a role of COL11A1 in the susceptibility to but not the severity of KBD.

Exploring Genome-wide DNA Methylation Profiles Altered in Kashin-Beck Disease Using Infinium Human Methylation 450 Bead Chips.

To understand how differentially methylated genes (DMGs) might affect the pathogenesis of Kashin-Beck disease (KBD). Genome-wide methylation profiling of whole blood from 12 matched KBD and controls pairs was performed using a high-resolution Infinium 450 K methylation array. In total, 97 CpG sites were differentially methylated in KBD compared to the normal controls; of these sites, 36 sites were significantly hypermethylated (covering 22 genes) and 61 sites were significantly hypomethylated (covering 34 genes). Of these genes, 14 significant pathways were identified, the most significant P value pathway was type I diabetes mellitus pathway and pathways associated with autoimmune diseases and inflammatory diseases were included in this study. Subsequently, 4 CpG sites in HLA-DRB1 were validated using bisulfite sequencing polymerase chain reaction (BSP) in articular cartilage, and the results showed significant differences in the methylation status between KBD and controls, consistent with the results of the high-resolution array. These results suggested that differences in genome-wide DNA methylation exist between KBD and the controls, and the biological pathways support the autoimmune disease and inflammatory disease hypothesis of KBD.