CDKAL1基因與胰島分泌功能及糖代謝指標(biāo)的相關(guān)性研究
發(fā)布時間：2018-07-14 17:41
【摘要】：目的探討東亞人群BMI相關(guān)基因CDKAL1在中國漢族人群中與胰島素抵抗、胰島素分泌功能以及糖代謝相關(guān)指標(biāo)的相關(guān)性,進一步探討該基因介導(dǎo)疾病發(fā)生發(fā)展的潛在分子機制,為疾病的早期干預(yù)及個性化基因治療的研究奠下基礎(chǔ)。方法以江蘇徐州地區(qū)社區(qū)的健康體檢人群為研究對象,共2313例,年齡18-81歲。所有研究對象的人體測量學(xué)指標(biāo)(身高、體重、血壓),生化檢測指標(biāo)(空腹血糖、空腹胰島素、餐后2h血糖、糖化血紅蛋白、血尿酸、甘油三酯、總膽固醇、高密度脂蛋白、低密度脂蛋白)均完整。胰島素抵抗及胰島素分泌以穩(wěn)態(tài)模型評估的胰島素抵抗指數(shù)(HOMA-IR)和胰島素分泌指標(biāo)(HOMA-B)來評價。應(yīng)用Taqman探針法檢測CDKAL1基因位點rs10946398的基因型,建立基因分型數(shù)據(jù)庫。運用SAS 9.1.3版軟件進行數(shù)據(jù)管理和統(tǒng)計分析。結(jié)果1CDKAL1基因rs10946398位點不同基因型之間年齡、血壓、空腹胰島素、HOMA-IR、甘油三酯、總膽固醇、高密度脂蛋白、低密度脂蛋白分布無差異,而C等位基因攜帶者空腹血糖水平明顯高于A等位基因攜帶者,并且HOMA-B水平明顯偏低。2.校正年齡、性別因素及BMI后,CDKAL1基因rs10946398位點C等位基因與HOMA-B有顯著相關(guān)性(Beta=-0.05,P0.0005),與HOMA-IR無相關(guān)性(Beta= 0.02, P = 0.08),進一步校正其他相關(guān)混雜因素后,這個相關(guān)性沒有明顯改變。3.校正年齡、性別因素及BMI后,rs10946398 C等位基因與糖代謝相關(guān)指標(biāo)(空腹血糖、餐后2h血糖、空腹胰島素、糖化血紅蛋白)有顯著相關(guān)性。4.校正年齡、性別因素及BMI后,CC基因型與胰島素抵抗和胰島素分泌受損發(fā)生相關(guān)風(fēng)險比值分別為：(OR=1.21,95％CI=1.04-1.41,P0.05；OR=1.29,95％CI =1.07-1.56,P0.01),進一步校正相關(guān)混雜因素后,與胰島素分泌受損相關(guān)性仍存在(P0.01),而與胰島素抵抗無明顯統(tǒng)計學(xué)意義(P=0.13)。結(jié)論1CDKAL1基因rs10946398位點C等位基因與HOMA-B有顯著相關(guān)性,并獨立于其他代謝危險因素。2.與A等位基因相比,攜帶rs10946398 C等位基因者的空腹血糖、餐后2h血糖水平、糖化血紅蛋白更高,并獨立于其他代謝危險因素。3.C等位基因與胰島素分泌受損發(fā)生的風(fēng)險相關(guān),而非胰島素抵抗,校正相關(guān)混雜因素后,這種相關(guān)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.
【學(xué)位授予單位】：東南大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2016
【分類號】：R587.1
本文編號：2122460
[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.
【學(xué)位授予單位】：東南大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2016
【分類號】：R587.1
【參考文獻】
相關(guān)期刊論文 前1條
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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