Association of the single nucleotide polymorphism of NOS3 gene with obesity in children aged 6~13 years

doi:10.11852/zgetbjzz2021-1179

Abstract

Abstract: Objective To analyze the correlation of polymorphisms of NOS3 rs1799983, rs2566508 with obesity in children aged 6 to 13, in order to provide scientific basis for further exploration of obesity occurrence, development, prevention and treatment. Methods A cross-sectional survey was conducted at a primary school in Shawan City, Xinjiang Province in September 2019. According to the inclusion and exclusion criteria, 100 cases were screened with obesity and 100 children were in control group. There were 122 cases of Han nationality and 78 cases of Kazakh. Chip capture sequencing and high-throughput sequencing technology were used to detect NOS3 gene rs1799983, rs2566508 polymorphism. Then their correlations with obesity among Han and Kazakh children were analyzed. Results 1) NOS3 gene rs2566508 polymorphism may be associated with obesity in Han girls aged 6 to 13 years. There were significant differences in the frequencies of T and G alleles distribution between the control group and obesity group (χ²=11.247, P=0.001). The risk of obesity increased significantly in carriers of G allele (OR=3.889, 95%CI:1.707 - 8.860). There were also significant differences in the frequencies of TT, TG and GG genotypes distribution between the two groups (χ²=10.389, P=0.004). However, no association between rs2566508 polymorphism and obesity was found in Han boys as well as Kazakh boys and girls. 2) The allele and genotype distribution frequencies of NOS3 gene rs1799983 were not statistically significant in the group differences between Han and Kazakh children (P＞0.05). Conclusion NOS3 gene rs2566508 polymorphism may be associated with obesity in Han girls aged 6 to 13, and the risk of obesity increases significantly in the carriers of G allele.

Key words: NOS3, single nucleotide polymorphism, obesity, children

摘要： 目的探讨NOS3基因rs1799983与rs2566508多态性与6～13岁儿童肥胖的相关性,为进一步探索肥胖的发生、发展、预防和治疗提供科学依据。方法 2019年9月在新疆沙湾市某小学进行横断面调查,按照纳入与排除标准,筛选出肥胖组和对照组儿童各100例,其中汉族儿童122例,哈萨克族儿童78例。采用芯片捕获测序技术、高通量测序技术检测NOS3基因rs1799983、rs2566508多态性,分析与汉族、哈萨克族儿童肥胖的相关性。结果 1)NOS3基因rs2566508多态性与汉族6～13岁女童的肥胖发生可能相关,T、G等位基因分布频率在对照组与肥胖组间差异有统计学意义(χ²=11.247,P=0.001),G等位基因携带者发生肥胖风险显著升高(OR=3.889,95%CI:1.707~8.860),TT、TG、GG基因型分布频率在两组间差异也有统计学意义(χ²=10.389,P=0.004)。但在汉族男童以及哈萨克族男童、女童中未发现rs2566508多态性与肥胖的相关性。2)NOS3基因rs1799983等位基因和基因型分布频率在汉族和哈萨克族儿童中组间差异无统计学意义(P＞0.05)。结论 NOS3基因rs2566508多态性与汉族6～13岁女童肥胖的发生可能相关,且G等位基因携带者发生肥胖风险显著升高。

关键词: NOS3, 单核苷酸多态性, 肥胖, 儿童

CLC Number:

R723.14

SHANG Li, XU Pei-ru, AIERKEN Aibibai, WANG Yi-lin. Association of the single nucleotide polymorphism of NOS3 gene with obesity in children aged 6~13 years[J]. Chinese Journal of Child Health Care, 2022, 30(5): 490-494.

尚黎, 徐佩茹, 艾比白·艾尔肯, 王一琳. NOS3单核苷酸多态性与6～13岁儿童肥胖的相关性[J]. 中国儿童保健杂志, 2022, 30(5): 490-494.

References

[1] NCD Risk Factor Collaboration. Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016:a pooled analysis of 2 416 population-based measurement studies in 128.9 million children, adolescents, and adults[J]. Lancet,2017,390(10113):2627-2642.
[2] Boyer BP, Nelson JA, Holub SC. Childhood BMI trajectories predicting cardiovascular risk in adolescence[J]. J Adolesc Health,2015,56(6):599-605.
[3] Younossi Z, Anstee QM, Marietti M, et al. Global burden of NAFLD and NASH:trends, predictions, risk factors and prevention[J]. Nat Rev Gastroenterol Hepatol,2018,15(1):11-20.
[4] Taylor R. Calorie restriction for long-term remission of type 2 diabetes[J]. Clin Med (Lond),2019,19(1):37-42.
[5] Bonsignore MR, Baiamonte P, Mazzuca E, et al. Obstructive sleep apnea and comorbidities:a dangerous liaison[J]. Multidiscip Respir Med,2019,14:8.
[6] Ansari S, Haboubi H, Haboubi N. Adult obesity complications:challenges and clinical impact[J]. Ther Adv Endocrinol Metab,2020,11:1-14.
[7] Furer A, Afek A, Sommer A, et al. Adolescent obesity and midlife cancer risk:a population-based cohort study of 2.3 million adolescents in Israel[J]. Lancet Diabetes Endocrinol,2020,8(3):216-225.
[8] Lee EY, Yoon KH. Epidemic obesity in children and adolescents:risk factors and prevention[J]. Front Med,2018,12(6):658-666.
[9] Ward ZJ, Long MW, Resch SC, et al. Simulation of growth trajectories of childhood obesity into adulthood[J]. N Engl J Med,2017,377(22):2145-2153.
[10] Llewellyn A, Simmonds M, Owen CG, et al. Childhood obesity as a predictor of morbidity in adulthood:a systematic review and meta-analysis[J]. Obes Rev,2016,17(1):56-67.
[11] Geserick M, Vogel M, Gausche R, et al. Acceleration of BMI in early childhood and risk of sustained obesity[J]. N Engl J Med, 2018,379(14):1303-1312.
[12] Król M, Kepinska M. Human nitric oxide synthase-its functions, polymorphisms, and inhibitors in the context of inflammation, diabetes and cardiovascular diseases[J]. Int J Mol Sci, 2020,22(1):56.
[13] Heinonen I, Saltin B, Kemppainen J, et al. Effect of nitric oxide synthase inhibition on the exchange of glucose and fatty acids in human skeletal muscle[J]. Nutr Metab (Lond), 2013,10(1):43.
[14] Canová NK, Lincová D, Kmonícková E, et al. Nitric oxide production from rat adipocytes is modulated by beta3-adrenergic receptor agonists and is involved in a cyclic AMP-dependent lipolysis in adipocytes[J]. Nitric Oxide, 2006,14(3):200-211.
[15] 中国肥胖问题工作组,季成叶.中国学龄儿童青少年超重、肥胖筛查体重指数值分类标准[J].中华流行病学杂志,2004,25(2):97-102.
[16] NCD Risk Factor Collaboration. Trends in adult body-mass index in 200 countries from 1975 to 2014:a pooled analysis of 1698 population-based measurement studies with 19.2 million participants[J]. Lancet, 2016,387(10026):1377-1396.
[17] 房红芸,翟屹,赵丽云,等. 中国6～17岁儿童青少年超重肥胖流行特征[J]. 中华流行病学杂志,2018,39(6):724-727.
[18] 徐佩茹,张卫平,阿依古丽,等. 新疆维、哈、回、汉族学龄儿童肥胖因素分析调查[J]. 新疆医学,2003,24(2):87-88.
[19] 储嘉慧,郑雨潇,余章斌,等. 中国0～7岁儿童单纯性肥胖症流行病学Meta分析[J]. 中华实用儿科临床杂志,2013,28(7):506-509.
[20] Twig G, Yaniv G, Levine H, et al. Body-mass index in 2.3 million adolescents and cardiovascular death in Adulthood[J]. N Engl J Med,2016,374(25):2430-2440.
[21] Bluher M. Adipose tissue inflammation:a cause or consequence of obesity-related insulin resistance?[J]. Clin Sci(Lond),2016,130(18):1603-1614.
[22] Caprio S, Santoro N, Weiss R. Childhood obesity and the associated rise in cardiometabolic complications[J]. Nat Metab,2020,2(3):223-232.
[23] Chung ST, Onuzuruike AU, Magge SN. Cardiometabolic risk in obese children[J]. Ann NY Acad Sci,2018,1411(1):166-183.
[24] Nasr HB, Dimassi S, M'hadhbi R, et al. Functional G894T (rs1799983) polymorphism and intron-4 VNTR variant of nitric oxide synthase (NOS3) gene are susceptibility biomarkers of obesity among Tunisians[J]. Obes Res Clin Pract,2016,10(4):465-475.
[25] de Miranda JA, Lacchini R, Belo VA, et al. The effects of endothelial nitric oxide synthase tagSNPs on nitrite levels and risk of hypertension and obesity in children and adolescents[J]. J Hum Hypertens,2015,29(2):109-114.
[26] Souza-Costa DC, Belo VA, Silva PS, et al. eNOS haplotype associated with hypertension in obese children and adolescents[J]. Int J Obes (Lond),2011,35(3):387-392.