瘦素受体Gln223Arg基因多态性与2型糖尿病患者合并非酒精性脂肪性肝病的相关性研究
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摘要
目的研究瘦素受体Gln223Arg基因多态性与T2DM患者合并非酒精性脂肪性肝病(NAFLD)的关系。方法选取2016年3～12月于华北理工大学附属医院内分泌科住院的T2DM患者234例,根据是否合并NAFLD分为单纯T2DM(T2DM组)120例和NAFLD组114例。采用聚合酶链反-限制性片段长度多态性(PCR-RFLP)检验瘦素受体Gln223Arg基因多态性。结果 T2DM组AA、AG、GG基因频率分别为31. 7%、53. 3%、15. 0%,NAFLD组AA、AG、GG基因频率分别为18. 4%、33. 33%、48. 2%,NAFLD组GG基因频率(48. 2%)大于T2DM组(15. 0%)(χ~2=30. 145,P<0. 01)。NAFLD组G等位基因频率(59. 7%)高于T2DM组(40. 3%)(χ~2=25. 363,P<0. 01)。多因素Logistic回归分析结果显示,GG基因型能增加NAFLD发病风险(P<0. 01);携带GG基因的危险增加了10. 181倍(95%CI 3. 460～29. 957)(P<0. 01)。结论T2DM患者携带GG基因型可能是NAFLD的易感因素。
Objective To explore the relationship between Gln223 Arg polymorphism in leptin receptor gene(LEPR) and nonalcoholic fatty liver disease(NAFLD) in patients with type 2 diabetes mellitus(T2DM). Methods A total of 234 hospitalized patients with T2DM in the Department of Endocrinology in the Affiliated Hospital of North China University of Technology were enrolled in this study in 2016. All the patients were divided into two groups: patients without NAFLD(T2DM group, n= 120) and patients with NAFLD(NAFLD group, n=114). Genotyping of Glb223 Arg was conducted by PCR-RFLP.Results The frequencies of AA,AG and GG genotypes were 31. 7%,53. 3% and 15. 0% in T2DM group respectively. The frequencies of AA, AG and GG genotype were 18. 4%, 33. 33% and 48. 2% in NAFLD group respectively. The frequency of GG genotype was higher in NAFLD group(48.2%) than in T2DM group(15.0%)(χ~2= 30.145, P<0.01). The frequency of G allele was also significantly higher in NAFLD group(59.7%) than in T2DM group(40.3%)(χ~2= 25.363, P<0.01). Multivariate logistic regression analysis showed that the GG genotype could significantly increase the risk of NAFLD(P< 0. 01) by a factor of 10.181(95 % CI 3. 460～29. 957). Conclusion GG genotype might be a factor of susceptibility for NAFLD in patients with T2DM.
Objective To explore the relationship between Gln223 Arg polymorphism in leptin receptor gene(LEPR) and nonalcoholic fatty liver disease(NAFLD) in patients with type 2 diabetes mellitus(T2DM). Methods A total of 234 hospitalized patients with T2DM in the Department of Endocrinology in the Affiliated Hospital of North China University of Technology were enrolled in this study in 2016. All the patients were divided into two groups: patients without NAFLD(T2DM group, n= 120) and patients with NAFLD(NAFLD group, n=114). Genotyping of Glb223 Arg was conducted by PCR-RFLP.Results The frequencies of AA,AG and GG genotypes were 31. 7%,53. 3% and 15. 0% in T2DM group respectively. The frequencies of AA, AG and GG genotype were 18. 4%, 33. 33% and 48. 2% in NAFLD group respectively. The frequency of GG genotype was higher in NAFLD group(48.2%) than in T2DM group(15.0%)(χ~2= 30.145, P<0.01). The frequency of G allele was also significantly higher in NAFLD group(59.7%) than in T2DM group(40.3%)(χ~2= 25.363, P<0.01). Multivariate logistic regression analysis showed that the GG genotype could significantly increase the risk of NAFLD(P< 0. 01) by a factor of 10.181(95 % CI 3. 460～29. 957). Conclusion GG genotype might be a factor of susceptibility for NAFLD in patients with T2DM.
引文
[1]李小飞,陈宇.2型糖尿病患者胰岛素抵抗与非酒精性脂肪肝的关系研究.中国医药指南,2010,8:23-24.
[2] Pagadala MR, Mccullough AJ. Non-alcoholic fatty liver disease and obesity:Not all about body mass index. Am J Gastroenterol,2012,107:1859-1861.
[3] Wang JP, Yang LT. Correlation between serum chemerin level and HOMA-IR, Hs-CPR of patients with nonalcoholic fatty liver disease. World Latest Medicine Information,2017.
[4] Liu J,Han L,Zhu L,et al. Free fatty acids,not triglycerides,are associated with non-alcoholic liver injury progression in high fat diet induced obese rats. Lipids Health Dis,2016,15:27.
[5]中华医学会肝病学分会脂肪肝和酒精性肝病学组.酒精性肝病诊疗指南.实用肝脏病杂志,2007,10:164-166.
[6]刘锐,张晓妍,李凤华.糖尿病合并非酒精性脂肪肝与血脂紊乱关系的研究.中国医药导报,2009,6:41-42.
[7] Wang YZ, Xiang GY, Lin L, et al. A correlation analysis of leptin and type 2 diabetes mellitus. China J Mod Med,2007,58:143-149.
[8] Fischer S,Hanefeld M,Haffner SM,et al. Insulin-resistant patients with type 2 diabetes mellitus have higher serum leptin levels independently of body fat mass. Acta Diabetol, 2002,39:105-110.
[9] Considine RV, Considine EL, Williams CJ, et al. The hypothalamic leptin receptor in humans:Identification of incidental sequence polymorphisms and absence of the db/db mouse and fa/fa rat mutations. Diabetes, 1996,45:992-994.
[10] Girard J. Is leptin the link between obesity and insulin resistance?. Diabetes&Metabolism,1997,23:16-24.
[11]张阳丹,李革,张名均,等.瘦素受体基因Gln223Arg多态性与2型糖尿病的关系.第三军医大学学报,2011,33:1932-1934.
[12] Becer E, Mehmetcik G, Bareke H, et al. Association of leptin re-ceptor gene Q223R polymorphism on lipid profiles in comparison study between obese and non-obese subjects. Gene, 2013,529:16-20.
[13]Shabana NA, Hasnain S. Association of the leptin receptor Gln223 Arg polymorphism with lipid profile in obese Pakistani subjects. Nutr, 2015,31:1136-1140.
[14]王春萍,张明.瘦素受体基因Gln223Arg多态性与非酒精性脂肪性肝病的关系.临床肝胆病杂志,2008,24:194-196.
[15]李敏,周健,史丽萍.非酒精性脂肪肝发病机制研究进展.陕西医学杂志,2012,41:1399-1400.
[16]黄雪芳,吴胜利,黄丽娟,等.维吾尔族、汉族2型糖尿病合并非酒精性脂肪肝的临床相关因素分析.中国医药指南,2015,13:62.
[2] Pagadala MR, Mccullough AJ. Non-alcoholic fatty liver disease and obesity:Not all about body mass index. Am J Gastroenterol,2012,107:1859-1861.
[3] Wang JP, Yang LT. Correlation between serum chemerin level and HOMA-IR, Hs-CPR of patients with nonalcoholic fatty liver disease. World Latest Medicine Information,2017.
[4] Liu J,Han L,Zhu L,et al. Free fatty acids,not triglycerides,are associated with non-alcoholic liver injury progression in high fat diet induced obese rats. Lipids Health Dis,2016,15:27.
[5]中华医学会肝病学分会脂肪肝和酒精性肝病学组.酒精性肝病诊疗指南.实用肝脏病杂志,2007,10:164-166.
[6]刘锐,张晓妍,李凤华.糖尿病合并非酒精性脂肪肝与血脂紊乱关系的研究.中国医药导报,2009,6:41-42.
[7] Wang YZ, Xiang GY, Lin L, et al. A correlation analysis of leptin and type 2 diabetes mellitus. China J Mod Med,2007,58:143-149.
[8] Fischer S,Hanefeld M,Haffner SM,et al. Insulin-resistant patients with type 2 diabetes mellitus have higher serum leptin levels independently of body fat mass. Acta Diabetol, 2002,39:105-110.
[9] Considine RV, Considine EL, Williams CJ, et al. The hypothalamic leptin receptor in humans:Identification of incidental sequence polymorphisms and absence of the db/db mouse and fa/fa rat mutations. Diabetes, 1996,45:992-994.
[10] Girard J. Is leptin the link between obesity and insulin resistance?. Diabetes&Metabolism,1997,23:16-24.
[11]张阳丹,李革,张名均,等.瘦素受体基因Gln223Arg多态性与2型糖尿病的关系.第三军医大学学报,2011,33:1932-1934.
[12] Becer E, Mehmetcik G, Bareke H, et al. Association of leptin re-ceptor gene Q223R polymorphism on lipid profiles in comparison study between obese and non-obese subjects. Gene, 2013,529:16-20.
[13]Shabana NA, Hasnain S. Association of the leptin receptor Gln223 Arg polymorphism with lipid profile in obese Pakistani subjects. Nutr, 2015,31:1136-1140.
[14]王春萍,张明.瘦素受体基因Gln223Arg多态性与非酒精性脂肪性肝病的关系.临床肝胆病杂志,2008,24:194-196.
[15]李敏,周健,史丽萍.非酒精性脂肪肝发病机制研究进展.陕西医学杂志,2012,41:1399-1400.
[16]黄雪芳,吴胜利,黄丽娟,等.维吾尔族、汉族2型糖尿病合并非酒精性脂肪肝的临床相关因素分析.中国医药指南,2015,13:62.