CDKAL1基因与胰岛分泌功能及糖代谢指标的相关性研究
发布时间：2018-07-14 17:41
【摘要】：目的探讨东亚人群BMI相关基因CDKAL1在中国汉族人群中与胰岛素抵抗、胰岛素分泌功能以及糖代谢相关指标的相关性,进一步探讨该基因介导疾病发生发展的潜在分子机制,为疾病的早期干预及个性化基因治疗的研究奠下基础。方法以江苏徐州地区社区的健康体检人群为研究对象,共2313例,年龄18-81岁。所有研究对象的人体测量学指标(身高、体重、血压),生化检测指标(空腹血糖、空腹胰岛素、餐后2h血糖、糖化血红蛋白、血尿酸、甘油三酯、总胆固醇、高密度脂蛋白、低密度脂蛋白)均完整。胰岛素抵抗及胰岛素分泌以稳态模型评估的胰岛素抵抗指数(HOMA-IR)和胰岛素分泌指标(HOMA-B)来评价。应用Taqman探针法检测CDKAL1基因位点rs10946398的基因型,建立基因分型数据库。运用SAS 9.1.3版软件进行数据管理和统计分析。结果1CDKAL1基因rs10946398位点不同基因型之间年龄、血压、空腹胰岛素、HOMA-IR、甘油三酯、总胆固醇、高密度脂蛋白、低密度脂蛋白分布无差异,而C等位基因携带者空腹血糖水平明显高于A等位基因携带者,并且HOMA-B水平明显偏低。2.校正年龄、性别因素及BMI后,CDKAL1基因rs10946398位点C等位基因与HOMA-B有显著相关性(Beta=-0.05,P0.0005),与HOMA-IR无相关性(Beta= 0.02, P = 0.08),进一步校正其他相关混杂因素后,这个相关性没有明显改变。3.校正年龄、性别因素及BMI后,rs10946398 C等位基因与糖代谢相关指标(空腹血糖、餐后2h血糖、空腹胰岛素、糖化血红蛋白)有显著相关性。4.校正年龄、性别因素及BMI后,CC基因型与胰岛素抵抗和胰岛素分泌受损发生相关风险比值分别为：(OR=1.21,95％CI=1.04-1.41,P0.05；OR=1.29,95％CI =1.07-1.56,P0.01),进一步校正相关混杂因素后,与胰岛素分泌受损相关性仍存在(P0.01),而与胰岛素抵抗无明显统计学意义(P=0.13)。结论1CDKAL1基因rs10946398位点C等位基因与HOMA-B有显著相关性,并独立于其他代谢危险因素。2.与A等位基因相比,携带rs10946398 C等位基因者的空腹血糖、餐后2h血糖水平、糖化血红蛋白更高,并独立于其他代谢危险因素。3.C等位基因与胰岛素分泌受损发生的风险相关,而非胰岛素抵抗,校正相关混杂因素后,这种相关性依然存在。
[Abstract]:Objective to investigate the association of BMI related gene CDKAL1 with insulin resistance, insulin secretion function and glucose metabolism in Chinese Han population, and to explore the potential molecular mechanism of CDKAL1 gene mediated disease development. To lay a foundation for the early intervention of disease and the research of individualized gene therapy. Methods 2313 healthy people aged 18-81 years were studied in the community of Xuzhou, Jiangsu province. All subjects' anthropometric parameters (height, weight, blood pressure), biochemical parameters (fasting blood glucose, fasting insulin, postprandial 2 h blood glucose, glycosylated hemoglobin, serum uric acid, triglyceride, total cholesterol, high density lipoprotein), Low density lipoprotein (LDL) is intact. Insulin resistance and insulin secretion were evaluated by homeostasis assessment of insulin resistance index (HOMA-IR) and insulin secretion index (HOMA-B). The genotypes of CDKAL1 locus rs10946398 were detected by Taqman probe method and the genotyping database was established. Data management and statistical analysis were carried out with SAS 9.1.3 software. Results 1there was no difference in age, blood pressure, fasting insulin HOMA-IRR, triglyceride, total cholesterol, high density lipoprotein and low density lipoprotein between different genotypes of CDKAL1 gene. The fasting blood glucose level of C allele carriers was significantly higher than that of A allele carriers, and HOMA-B level was significantly lower than that of A allele carriers. Adjusted age, sex factors and C allele of rs10946398 locus of CDKAL1 gene were significantly correlated with HOMA-B (Betaeg-0.05, P0.0005), but not with HOMA-IR (Beta = 0.02, P = 0.08). After further adjusting for other related confounding factors, the correlation was not significantly changed by .3. Adjusted age, sex factors and rs10946398 C allele after BMI were significantly correlated with glucose metabolism (fasting blood glucose, postprandial 2 h blood glucose, fasting insulin, glycosylated hemoglobin). Adjusted age, sex factors and the risk ratio of CC genotype to insulin resistance and impaired insulin secretion after BMI were as follows: (OR1. 21 / 95 CI 1.04-1. 41 ~ 1. 01 P0. 05 CI 1.2995 CI 1.07-1 56 P0.01), and after further adjusting for the associated confounding factors, There was still correlation with insulin secretion impairment (P0.01), but not with insulin resistance (P0. 13). Conclusion 1the C allele of rs10946398 locus of CDKAL1 gene is significantly correlated with HOMA-B and independent of other metabolic risk factors. Compared with the A allele, the fasting blood glucose, 2 h postprandial glucose level and glycosylated hemoglobin were higher in the patients with rs10946398 C allele, and were independent of other metabolic risk factors. 3. C allele was associated with the risk of impaired insulin secretion. And non-insulin resistance, adjusted for the associated confounding factors, this correlation still exists.
【学位授予单位】：东南大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R587.1
本文编号：2122462
[Abstract]:Objective to investigate the association of BMI related gene CDKAL1 with insulin resistance, insulin secretion function and glucose metabolism in Chinese Han population, and to explore the potential molecular mechanism of CDKAL1 gene mediated disease development. To lay a foundation for the early intervention of disease and the research of individualized gene therapy. Methods 2313 healthy people aged 18-81 years were studied in the community of Xuzhou, Jiangsu province. All subjects' anthropometric parameters (height, weight, blood pressure), biochemical parameters (fasting blood glucose, fasting insulin, postprandial 2 h blood glucose, glycosylated hemoglobin, serum uric acid, triglyceride, total cholesterol, high density lipoprotein), Low density lipoprotein (LDL) is intact. Insulin resistance and insulin secretion were evaluated by homeostasis assessment of insulin resistance index (HOMA-IR) and insulin secretion index (HOMA-B). The genotypes of CDKAL1 locus rs10946398 were detected by Taqman probe method and the genotyping database was established. Data management and statistical analysis were carried out with SAS 9.1.3 software. Results 1there was no difference in age, blood pressure, fasting insulin HOMA-IRR, triglyceride, total cholesterol, high density lipoprotein and low density lipoprotein between different genotypes of CDKAL1 gene. The fasting blood glucose level of C allele carriers was significantly higher than that of A allele carriers, and HOMA-B level was significantly lower than that of A allele carriers. Adjusted age, sex factors and C allele of rs10946398 locus of CDKAL1 gene were significantly correlated with HOMA-B (Betaeg-0.05, P0.0005), but not with HOMA-IR (Beta = 0.02, P = 0.08). After further adjusting for other related confounding factors, the correlation was not significantly changed by .3. Adjusted age, sex factors and rs10946398 C allele after BMI were significantly correlated with glucose metabolism (fasting blood glucose, postprandial 2 h blood glucose, fasting insulin, glycosylated hemoglobin). Adjusted age, sex factors and the risk ratio of CC genotype to insulin resistance and impaired insulin secretion after BMI were as follows: (OR1. 21 / 95 CI 1.04-1. 41 ~ 1. 01 P0. 05 CI 1.2995 CI 1.07-1 56 P0.01), and after further adjusting for the associated confounding factors, There was still correlation with insulin secretion impairment (P0.01), but not with insulin resistance (P0. 13). Conclusion 1the C allele of rs10946398 locus of CDKAL1 gene is significantly correlated with HOMA-B and independent of other metabolic risk factors. Compared with the A allele, the fasting blood glucose, 2 h postprandial glucose level and glycosylated hemoglobin were higher in the patients with rs10946398 C allele, and were independent of other metabolic risk factors. 3. C allele was associated with the risk of impaired insulin secretion. And non-insulin resistance, adjusted for the associated confounding factors, this correlation still exists.
【学位授予单位】：东南大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R587.1
【参考文献】
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1 Sawako Kuruma;Naoto Egawa;Masanao Kurata;Goro Honda;Terumi Kamisawa;Junko Ueda;Hiroshi Ishii;Makoto Ueno;Haruhisa Nakao;Mitsuru Mori;Keitaro Matsuo;Satoyo Hosono;Shinichi Ohkawa;Kenji Wakai;Kozue Nakamura;Akiko Tamakoshi;Masanori Nojima;Mami Takahashi;Kazuaki Shimada;Takeshi Nishiyama;Shogo Kikuchi;Yingsong Lin;;case-control study of diabetes-related genetic variants and pancreatic cancer risk in Japan[J];World Journal of Gastroenterology;2014年46期
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