Abstract 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.
SHI Xiao-Wei,LYU Ai-Li,WANG Sen et al. Heritability of obesity in children aged 30-36 months and an analysis of single nucleotide polymorphisms at four loci in Xi’an, China[J]. CJCP, 2020, 22(4): 355-360.
SHI Xiao-Wei,LYU Ai-Li,WANG Sen et al. Heritability of obesity in children aged 30-36 months and an analysis of single nucleotide polymorphisms at four loci in Xi’an, China[J]. CJCP, 2020, 22(4): 355-360.
Lakshman R, Clifton EA, Ong KK. Baby-led weaning-safe and effective but not preventive of obesity[J]. JAMA Pediatr, 2017, 171(9):832-833.
[2]
Gamboa Delgado EM, Rangel-Díaz YA, Gutiérrez-Gómez YY. Association between birth weight and cardiometabolic risk factors in children of Bucaramanga, Colombia[J]. Nutr Hosp, 2017, 34(5):1105-1111.
[3]
Sogunle E, Masukume G, Nelson G. The association between caesarean section delivery and later life obesity in 21-24 year olds in an Urban South African birth cohort[J]. PLoS One, 2019, 14(11):e0221379.
Wen W, Cho YS, Zheng W, et al. Meta-analysis identifies common variants associated with body mass index in East Asians[J]. Nat Genet, 2012, 44(3):307-311.
[8]
Okada Y, Kubo M, Ohmiya H, et al. Common variants at CDKAL1 and KLF9 are associated with body mass index in East Asian populations[J]. Nat Genet, 2012, 44(3):302-306.
Cnattingius S, Villamor E, Lagerros YT, et al. High birth weight and obesity-a vicious circle across generations[J]. Int J Obes (Lond), 2012, 36(10):1320-1324.
[13]
Lindgren MP, PirouziFard M, Smith JG, et al. A Swedish nationwide adoption study of the heritability of heart failure[J]. JAMA Cardiol, 2018, 3(8):703-710.
[14]
Shi X, Lv A, Ma J, et al. Investigation of MMP-1 genetic polymorphisms and protein expression and their effects on the risk of Kashin-Beck disease in the Northwest Chinese Han population[J]. J Orthop Surg Res, 2016, 11(1):64.
[15]
Elks CE, den Hoed M, Zhao JH, et al. Variability in the heritability of body mass index:a systematic review and metaregression[J]. Front Endocrinol (Lausanne), 2012, 3:29.
[16]
Schrempft S, van Jaarsveld CHM, Fisher A, et al. Variation in the heritability of child body mass index by obesogenic home environment[J]. JAMA Pediatr, 2018, 172(12):1153-1160.
Donkin I, Versteyhe S, Ingerslev LR, et al. Obesity and bariatric surgery drive epigenetic variation of spermatozoa in humans[J]. Cell Metab, 2016, 23(2):369-378.
[19]
Roy SM, Chesi A, Mentch F, et al. Body mass index (BMI) trajectories in infancy differ by population ancestry and may presage disparities in early childhood obesity[J]. J Clin Endocrinol Metab, 2015, 100(4):1551-1560.
[20]
Lindsay KL, Brennan L, Rath A, et al. Gestational weight gain in obese pregnancy:impact on maternal and foetal metabolic parameters and birthweight[J]. J Obstet Gynaecol, 2018, 38(1):60-65.
[21]
Zhou Z, Lin Q, Xu X, et al. Maternal high-fat diet impairs follicular development of offspring through intraovarian kisspeptin/GPR54 system[J]. Reprod Biol Endocrinol, 2019, 17(1):13.
[22]
Tian Y, Xu J, Huang T, et al. A novel polymorphism (rs35612982) in CDKAL1 is a risk factor of type 2 diabetes:a case-control study[J]. Kidney Blood Press Res, 2019, 44(6):1313-1316.
[23]
Andersson EA, Pilgaard K, Pisinger C, et al. Type 2 diabetes risk alleles near ADCY5, CDKAL1 and HHEX-IDE are associated with reduced birthweight[J]. Diabetologia, 2010, 53(9):1908-1916.
[24]
Winkler C, Bonifacio E, Grallert H, et al. BMI at age 8 years is influenced by the type 2 diabetes susceptibility genes HHEXIDE and CDKAL1[J]. Diabetes, 2010, 59(8):2063-2067.
[25]
Wang HJ, Hinney A, Song JY, et al. Association of common variants identified by recent genome-wide association studies with obesity in Chinese children:a case-control study[J]. BMC Med Genet, 2016, 17:7.
[26]
Fu J, Li G, Li L, et al. The role of established East Asian obesity-related loci on pediatric leptin levels highlights a neuronal influence on body weight regulation in Chinese children and adolescents:the BCAMS study[J]. Oncotarget, 2017, 8(55):93593-93607.
[27]
Parimisetty A, Dorsemans AC, Awada R, et al. Secret talk between adipose tissue and central nervous system via secreted factors-an emerging frontier in the neurodegenerative research[J]. J Neuroinflammation, 2016, 13(1):67.
[28]
Fasshauer M, Blüher M. Adipokines in health and disease[J]. Trends Pharmacol Sci, 2015, 36(7):461-470.
