中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 37 Issue 6
Jun.  2021
Turn off MathJax
Article Contents

KCNJ11 rs5210 polymorphism and genetic susceptibility to nonalcoholic fatty liver disease and coronary artery disease

DOI: 10.3969/j.issn.1001-5256.2021.06.027
  • Received Date: 2020-11-06
  • Accepted Date: 2020-12-17
  • Published Date: 2021-06-20
  •   Objective  To investigate the association of KCNJ11 rs5210 single nucleotide polymorphism with nonalcoholic fatty liver disease (NAFLD) and coronary artery disease (CAD) in the Chinese Han population in Qingdao, China.  Methods  A total of 246 patients with NAFLD who attended Qingdao Municipal Hospital from December 2018 to September 2019 were enrolled as NAFLD group, 201 patients with CAD were enrolled as CAD group, and 116 patients with NAFLD and CAD were enrolled as NAFLD+CAD group; 342 healthy individuals were enrolled as control group. Fasting venous blood samples were collected for biochemical analysis. Whole blood genomic DNA was extracted, and PCR was used to determine KCNJ11 rs5210 genotype. The chi-square test was used to analyze whether the distribution of KCNJ11 rs5210 gene frequencies met the Hardy-Weinberg equilibrium, in order to determine whether the tested samples could represent the population. The chi-square test was used to analyze the differences in sex and genotype/allele frequency between groups. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups; the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups, and the Bonferroni method was used for further comparison between two groups. The unconditional logistic regression model was used to calculate odds ratio (OR) and 95% confidence interval.  Results  Three genotypes (AA, GA, and GG) of KCNJ11 rs5210 were found by gene sequencing. There were no significant differences in rs5210 allele frequency and genotype distribution between the control group, the NAFLD group, the CAD group, and the NAFLD+CAD group (all P > 0.05), and there were still no significant differences after adjustment for sex, age, and body mass index (BMI) (all P > 0.05). For all subjects, the subjects with AA genotype had a higher level of alkaline phosphatase than those with GA genotype (P=0.048); in the NAFLD group, the patients with GA genotype had significantly higher BMI and total bilirubin than those with AA genotype (P=0.042 and 0.002). The unconditional logistic regression analysis showed that elevated BMI was associated with the risk of NAFLD (OR=1.35, P < 0.01), while decreased high-density lipoprotein (HDL) might indicate an increase in the risk of NAFLD (OR=0.33, P < 0.01); elevated fasting plasma glucose and decreased HDL might indicate an increase in the risk of CAD (OR=1.51 and 0.11, both P < 0.01) and NAFLD with CAD (OR=1.46 and 0.06, both P < 0.01).  Conclusion  There is no significant association between KCNJ11 rs5210 polymorphism and the risk of NAFLD and CAD in the Chinese Han population in Qingdao.

     

  • loading
  • [1]
    National Workshop on Fatty Liver and Alcoholic Liver Disease, Chinese Society of Hepatology, Chinese Medical Association; Fatty Liver Expert Committee, Chinese Medical Doctor Association. Guidelines of prevention and treatment for nonalcoholic fatty liver disease: A 2018 update[J]. J Clin Hepatol, 2018, 34(5) : 947-957. DOI: 10.3969/j.issn.1001-5256.2018.05.007.

    中华医学会肝病学分会脂肪肝和酒精性肝病学组, 中国医师协会脂肪性肝病专家委员会. 非酒精性脂肪性肝病防治指南(2018年更新版)[J]. 临床肝胆病杂志, 2018, 34(5): 947-957. DOI: 10.3969/j.issn.1001-5256.2018.05.007.
    [2]
    LIN SC, FENG G, LIU JL, et al. From nonalcoholic fatty liver disease to metabolic fatty liver disease: An analysis based on disease heterogeneity[J]. J Clin Hepatol, 2020, 36(11): 2597-2600. DOI: 10.3969/j.issn.1001-5256.2020.11.045.

    林思岑, 冯巩, 刘军林, 等. 从非酒精性脂肪性肝病到代谢性脂肪性肝病—基于疾病异质性角度的分析[J]. 临床肝胆病杂志, 2020, 36(11): 2597-2600. DOI: 10.3969/j.issn.1001-5256.2020.11.045.
    [3]
    KHERA AV, KATHIRESAN S. Genetics of coronary artery disease: Discovery, biology and clinical translation[J]. Nat Rev Genet, 2017, 18(6): 331-344. DOI: 10.1038/nrg.2016.160.
    [4]
    PYXARAS SA, WIJNS W, REIBER J, et al. Invasive assessment of coronary artery disease[J]. J Nucl Cardiol, 2018, 25(3): 860-871. DOI: 10.1007/s12350-017-1050-5.
    [5]
    LABAZI H, TRASK AJ. Coronary microvascular disease as an early culprit in the pathophysiology of diabetes and metabolic syndrome[J]. Pharmacol Res, 2017, 123: 114-121. DOI: 10.1016/j.phrs.2017.07.004.
    [6]
    MUSSO G, GAMBINO R, CASSADER M, et al. Meta-analysis: Natural history of non-alcoholic fatty liver disease (NAFLD) and diagnostic accuracy of non-invasive tests for liver disease severity[J]. Ann Med, 2011, 43(8): 617-649. DOI: 10.3109/07853890.2010.518623.
    [7]
    ANSTEE QM, TARGHER G, DAY CP. Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis[J]. Nat Rev Gastroenterol Hepatol, 2013, 10(6): 330-344. DOI: 10.1038/nrgastro.2013.41.
    [8]
    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. DOI: 10.1038/nrgastro.2017.109.
    [9]
    VALENTI L, AL-SERRI A, DALY AK, et al. Homozygosity for the patatin-like phospholipase-3/adiponutrin I148M polymorphism influences liver fibrosis in patients with nonalcoholic fatty liver disease[J]. Hepatology, 2010, 51(4): 1209-1217. DOI: 10.1002/hep.23622.
    [10]
    ANSTEE QM, DAY CP. The genetics of nonalcoholic fatty liver disease: Spotlight on PNPLA3 and TM6SF2[J]. Semin Liver Dis, 2015, 35(3): 270-290. DOI: 10.1055/s-0035-1562947.
    [11]
    KOSTER JC, PERMUTT MA, NICHOLS CG. Diabetes and insulin secretion: The ATP-sensitive K+ channel (K ATP) connection[J]. Diabetes, 2005, 54(11): 3065-3072. DOI: 10.2337/diabetes.54.11.3065.
    [12]
    ABDELHAMID I, LASRAM K, MEILOUD G, et al. E23K variant in KCNJ11 gene is associated with susceptibility to type 2 diabetes in the Mauritanian population[J]. Prim Care Diabetes, 2014, 8(2): 171-175. DOI: 10.1016/j.pcd.2013.10.006.
    [13]
    QIU L, NA R, XU R, et al. Quantitative assessment of the effect of KCNJ11 gene polymorphism on the risk of type 2 diabetes[J]. PLoS One, 2014, 9(4): e93961. DOI: 10.1371/journal.pone.0093961.
    [14]
    SHIMOMURA K. The K(ATP) channel and neonatal diabetes[J]. Endocr J, 2009, 56(2): 165-175. DOI: 10.1507/endocrj.k08e-160.
    [15]
    BONNEFOND A, PHILIPPE J, DURAND E, et al. Whole-exome sequencing and high throughput genotyping identified KCNJ11 as the thirteenth MODY gene[J]. PLoS One, 2012, 7(6): e37423. DOI: 10.1371/journal.pone.0037423.
    [16]
    MARTHINET E, BLOC A, OKA Y, et al. Severe congenital hyperinsulinism caused by a mutation in the Kir6.2 subunit of the adenosine triphosphate-sensitive potassium channel impairing trafficking and function[J]. J Clin Endocrinol Metab, 2005, 90(9): 5401-5406. DOI: 10.1210/jc.2005-0202.
    [17]
    FEDELE F, MANCONE M, CHILIAN WM, et al. Role of genetic polymorphisms of ion channels in the pathophysiology of coronary microvascular dysfunction and ischemic heart disease[J]. Basic Res Cardiol, 2013, 108(6): 387. DOI: 10.1007/s00395-013-0387-4.
    [18]
    CENSIN JC, PETERS S, BOVIJN J, et al. Causal relationships between obesity and the leading causes of death in women and men[J]. PLoS Genet, 2019, 15(10): e1008405. DOI: 10.1371/journal.pgen.1008405.
    [19]
    BYRNE CD, TARGHER G. NAFLD: A multisystem disease[J]. J Hepatol, 2015, 62(1 Suppl): s47-s64. DOI: 10.1016/j.jhep.2014.12.012.
    [20]
    GAGGINI M, MORELLI M, BUZZIGOLI E, et al. Non-alcoholic fatty liver disease (NAFLD) and its connection with insulin resistance, dyslipidemia, atherosclerosis and coronary heart disease[J]. Nutrients, 2013, 5(5): 1544-1560. DOI: 10.3390/nu5051544.
    [21]
    National Workshop on Fatty Liver and Alcoholic Liver Disease, Chinese Society of Hepatology, Chinese Medical Association. Guidelines of diagnosis and treatment for nonalcoholic fatty liver disease: A 2010 update[J]. J Clin Hepatol, 2010, 26(2): 120-124. http://lcgdbzz.org/cn/article/doi/1001-5256%20(2010)%2002-0120-05

    中华医学会肝病学分会脂肪肝和酒精性肝病学组. 非酒精性脂肪性肝病诊疗指南(2010年修订版)[J]. 临床肝胆病杂志, 2010, 26(2): 120-124. http://lcgdbzz.org/cn/article/doi/1001-5256%20(2010)%2002-0120-05
    [22]
    HAO P. The Study of single nucleotide polymorphisms(SNPS) of KCNJ11 gene associated with type 2 diabetes of Chinese Koreans in Yanbian area[D]. Yanji: Yanbian University, 2012.

    郝萍. 延边地区朝鲜族KCNJ11基因单核苷酸多态性与2型糖尿病的相关性研究[D]. 延吉: 延边大学, 2012.
    [23]
    KHAN IA, VATTAM KK, JAHAN P, et al. Correlation between KCNQ1 and KCNJ11 gene polymorphisms and type 2 and post-transplant diabetes mellitus in the Asian Indian population[J]. Genes Dis, 2015, 2(3): 276-282. DOI: 10.1016/j.gendis.2015.02.009.
    [24]
    GALLARDO-BLANCO HL, VILLARREAL-PEREZ JZ, CERDA-FLORES RM, et al. Genetic variants in KCNJ11, TCF7L2 and HNF4A are associated with type 2 diabetes, BMI and dyslipidemia in families of Northeastern Mexico: A pilot study[J]. Exp Ther Med, 2017, 13(2): 523-529. DOI: 10.3892/etm.2016.3990.
    [25]
    KOO BK, CHO YM, PARK BL, et al. Polymorphisms of KCNJ11 (Kir6.2 gene) are associated with type 2 diabetes and hypertension in the Korean population[J]. Diabet Med, 2007, 24(2): 178-186. DOI: 10.1111/j.1464-5491.2006.02050.x.
    [26]
    SAKAMOTO Y, INOUE H, KESHAVARZ P, et al. SNPs in the KCNJ11-ABCC8 gene locus are associated with type 2 diabetes and blood pressure levels in the Japanese population[J]. J Hum Genet, 2007, 52(10): 781-793. DOI: 10.1007/s10038-007-0190-x.
    [27]
    ZHANCHENG W, WENHUI J, YUN J, et al. The dominant models of KCNJ11 E23K and KCNMB1 E65K are associated with essential hypertension (EH) in Asian: Evidence from a meta-analysis[J]. Medicine (Baltimore), 2019, 98(23): e15828. DOI: 10.1097/MD.0000000000015828.
    [28]
    KANE GC, BEHFAR A, DYER RB, et al. KCNJ11 gene knockout of the Kir6.2 KATP channel causes maladaptive remodeling and heart failure in hypertension[J]. Hum Mol Genet, 2006, 15(15): 2285-2297. DOI: 10.1093/hmg/ddl154.
    [29]
    ZHANG B, NOVITSKAYA T, WHEELER DG, et al. KCNJ11 ablation is associated with increased nitro-oxidative stress during ischemia-reperfusion injury: Implications for human ischemic cardiomyopathy[J]. Circ Heart Fail, 2017, 10(2): e003523. DOI: 10.1161/CIRCHEARTFAILURE.116.003523.
    [30]
    WEBER C, NOELS H. Atherosclerosis: Current pathogenesis and therapeutic options[J]. Nat Med, 2011, 17(11): 1410-1422. DOI: 10.1038/nm.2538.
    [31]
    XU Y, ZHAO Z, LIU S, et al. Association of nonalcoholic fatty liver disease and coronary artery disease with FADS2 rs3834458 gene polymorphism in the Chinese Han population[J]. Gastroenterol Res Pract, 2019, 2019: 6069870. DOI: 10.1155/2019/6069870.
    [32]
    ZHUANG L, ZHAO Y, ZHAO W, et al. The E23K and A190A variations of the KCNJ11 gene are associated with early-onset type 2 diabetes and blood pressure in the Chinese population[J]. Mol Cell Biochem, 2015, 404(1-2): 133-141. DOI: 10.1007/s11010-015-2373-7.
    [33]
    WEBSTER RJ, WARRINGTON NM, BEILBY JP, et al. The longitudinal association of common susceptibility variants for type 2 diabetes and obesity with fasting glucose level and BMI[J]. BMC Med Genet, 2010, 11: 140. DOI: 10.1186/1471-2350-11-140.
    [34]
    PECIOSKA S, ZILLIKENS MC, HENNEMAN P, et al. Association between type 2 diabetes loci and measures of fatness[J]. PLoS One, 2010, 5(1): e8541. DOI: 10.1371/journal.pone.0008541.
    [35]
    HOTTA K, KITAMOTO A, KITAMOTO T, et al. Association between type 2 diabetes genetic susceptibility loci and visceral and subcutaneous fat area as determined by computed tomography[J]. J Hum Genet, 2012, 57(5): 305-310. DOI: 10.1038/jhg.2012.21.
    [36]
    AGARWAL A K, JAIN V, SINGLA S, et al. Prevalence of non-alcoholic fatty liver disease and its correlation with coronary risk factors in patients with type 2 diabetes[J]. J Assoc Physicians India, 2011, 59: 351-354. DOI: 10.14260/jemds/2015/1174.
    [37]
    KATSIKI N, MIKHAILIDIS DP, MANTZOROS CS. Non-alcoholic fatty liver disease and dyslipidemia: An update[J]. Metabolism, 2016, 65(8): 1109-1123. DOI: 10.1016/j.metabol.2016.05.003.
    [38]
    KHAN V, VERMA AK, BHATT D, et al. Association of genetic variants of KCNJ11 and KCNQ1 genes with risk of type 2 diabetes mellitus (T2DM) in the Indian population: A case-control study[J]. Int J Endocrinol, 2020, 2020: 5924756. DOI: 10.1155/2020/5924756.
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Tables(5)

    Article Metrics

    Article views (412) PDF downloads(16) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return