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[摘要] 目的 探討青岛汉族人群中FABP2 rs1799883基因多态性与非乙醇性脂肪性肝病(NAFLD)以及冠状动脉粥样硬化性心脏病(CAD)的相关性。方法 纳入在青岛市市立医院就诊的296例住院病人,分为NAFLD组、CAD组、NAFLD合并CAD(合并组),以104名健康体检者作为对照组。采集临床信息,同时用聚合酶链反应(PCR)方法和质谱测序进行基因型检测。采用非条件Logistic回归模型分析基因型和等位基因与患病风险的关系。结果 FABP2 rs1799883的基因型分布在NAFLD组与对照组、合并组与对照组、合并组与NAFLD组间差异均无统计学意义,而在CAD组与对照组间差异有统计学意义(χ2=6.495,P<0.05)。4组FABP2 rs1799883等位基因频率比较差异均无统计学意义(P>0.05)。Logistic回归分析显示,FABP2 rs1799883 CT+TT基因型与CAD的发病风险显著相关,是CAD的保护因素(OR=0.50,95%CI=0.29~0.87,P<0.05);对性别、年龄进行校正后,CT+TT基因型仍然与CAD发病风险相关(OR=0.46,95%CI=0.24~0.90,P<0.05)。结论 在青岛汉族人群中,FABP2 rs1799883基因多态性与NAFLD以及NAFLD合并CAD的发病风险无明显相关性,但其CT+TT基因型与CAD的发病风险相关,是CAD的一种保护性因素。
[关键词] 脂肪酸结合蛋白质类;多态性,单核苷酸;非乙醇性脂肪性肝病;冠心病;青岛
[中图分类号] R575.5;R541.4 [文献标志码] A [文章编号] 2096-5532(2020)05-0549-05
doi:10.11712/jms.2096-5532.2020.56.171 [开放科学(资源服务)标识码(OSID)]
[ABSTRACT] Objective To investigate the association of FABP2 rs1799883 gene polymorphism with nonalcoholic fatty liver disease (NAFLD) and coronary artery disease (CAD) in the Chinese Han population in Qingdao, China. Methods A total of 296 inpatients admitted to Qingdao Municipal Hospital were included and divided into NAFLD group, CAD group, and NAFLD with CAD group. Another 104 healthy individuals who underwent physical examination were included as control group. After collection of clinical information, PCR and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry were used to determine the genotype of FABP2 rs1799883. The unconditional Logistic regression model was used to analyze the relationship of genotype and allele with disease risk. Results The genotype distribution of FABP2 rs1799883 was not significantly different between the NAFLD group and the control group, between the NAFLD with CAD group and the control group, and between the NAFLD with CAD group and the NAFLD group, but was significantly different between the CAD group and the control group (χ2=6.495,P<0.05). The allele frequency of FABP2 rs1799883 showed no significant difference between the four groups (P>0.05). The logistic regression analysis showed that FABP2 rs1799883 CT+TT genotype was significantly associated with the risk of CAD and was a protective factor against CAD (OR=0.50,95%CI=0.29-0.87,P<0.05). After adjustment for sex and age, CT+TT genotype was still associated with the risk of CAD (OR=0.46,95%CI=0.24-0.90,P<0.05). Conclusion Among the Chinese Han population in Qingdao, the FABP2 rs1799883 gene polymorphism is not significantly associated with the risk of NAFLD or NAFLD with CAD, but its CT+TT genotype is associated with the risk of CAD and is a protective factor against CAD. [KEY WORDS] fatty acid-binding proteins; polymorphism, single nucleotide; non-alcoholic fatty liver disease; coronary disease; Qingdao
非乙醇性脂肪性肝病(NAFLD)是指除乙醇外,由其他明确肝损伤因素所致的以肝细胞内脂肪过度沉积为主要特征的临床病理综合征。NAFLD的发展呈现一系列病理特征,包括单纯性非乙醇性脂肪肝、非乙醇性脂肪性肝炎、肝纤维化等,最终发展为肝癌[1]。近年来,NAFLD的患病率逐年上升,亚洲NAFLD患病率从2016年的27.4%上升到2019年的29.8%[2-3]。NAFLD的发生发展与2型糖尿病、肥胖等代谢综合征密切相关[3],其影响因素包括炎症、免疫、代谢、脂毒性、纤维化和基因等[4]。冠状动脉粥样硬化性心脏病(CAD)是指因冠状动脉发生管腔内狭窄或闭塞,继而致使心肌缺血或坏死所引起的心脏病。CAD的发病机制尚不完全明确。代谢综合征以及血脂水平的升高与CAD的发病风险明显相关[5]。
FABP2基因屬于FABP基因超家族,主要在小肠上皮细胞中表达,编码为包含132个氨基酸残基的分子量为15 100的肠道脂肪酸结合蛋白。而后者可以选择性结合未酯化的长链脂肪酸及其他配体,负责摄取膳食中的游离脂肪酸[6]。已有多项研究结果表明,FABP2调控人体脂肪代谢,可以促进肠道n-3多不饱和脂肪酸吸收,介导三酰甘油(TG)合成胆固醇[7-9]。FABP2基因多态性还与2型糖尿病相关[10-15]。FABP2与NAFLD、CAD的发病也有相关性。中国福建的一项研究显示,FABP2等位基因为A和T及TT基因型有更高的NAFLD风险[16]。美国的一项研究表明,FABP2 rs1799883 T等位基因携带者有更高的心肌梗死风险[17]。墨西哥的一项研究显示,FABP2 rs1799883 T等位基因携带者比非携带者有更高的心血管疾病风险[18]。在中国,尚无FABP2 rs1799883基因与CAD关系的研究报道。本研究对FABP2 rs1799883基因多态性与青岛汉族人群NAFLD和CAD发病风险的相关性进行探讨,从而为研究NAFLD、CAD的相关遗传发病机制提供新思路,并为将来可能实现的个体化基因治疗铺路。
1 对象与方法
1.1 研究对象
在医院伦理委员会的许可下,选取2018年1月—2019年9月于青岛市市立医院住院的病人296例,其中NAFLD病人90例(NAFLD组,B组)、CAD病人99例(CAD组,C组)、NAFLD合并CAD病人107例(NAFLD合并CAD组,简称合并组,D组);同时纳入104名健康体检者作为对照组(A组)。NAFLD诊断符合《非酒精性脂肪性肝病防治指南》的标准[19]并经B型超声检查证实。CAD经冠状动脉或其分支的冠状动脉造影诊断。同时排除乙醇性肝炎、病毒性和自身免疫性肝炎、药物性肝炎、妊娠急性脂肪肝等其他原因引起的肝脏疾病,以及主动脉夹层、心房颤动、风湿性免疫疾病、心肌病、大动脉炎等其他可能引起CAD的疾病。健康对照均通过生化指标结合超声检查确认。
1.2 标本采集及资料收集
受试者禁饮食12 h后,常规采集静脉血8 mL,分别取4 mL置入A、B两支EDTA抗凝管中。A管用于检测生化指标,包括丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、空腹血糖(FBG)、TG、总胆固醇(TC)、高密度脂蛋白(HDL)以及低密度脂蛋白(LDL)等。B管离心后置于-80 ℃冰箱中保存备用。使用标准问卷调查研究对象姓名、性别、年龄等基本信息,用专业仪表测量身高和体质量,并计算体质量指数(BMI)。
1.3 全血基因组DNA的提取和检测
应用血液基因组DNA提取试剂盒(北京博淼生物科技有限公司)提取全血基因组DNA。采用聚合酶链反应(PCR)方法检测FABP2基因rs179983位点多态性。所用的PCR引物由北京博淼生物科技有限公司设计合成,序列如下:上游引物5′-ACG-TTGGATGGCTGACAATTACACAAGAAGG-3′,下游引物5′-ACGTTGGATGGGTGACACCAAG-TTCAAAAAC-3′。PCR扩增反应后,将PCR产物用虾碱性磷酸酶(SAP)处理,之后进行单碱基延伸反应、树脂纯化及芯片点样。最后进行质谱检测分析基因型。
1.4 统计学方法
使用SPSS 21.0(Windows 10)软件进行统计学分析。4组一般临床资料比较时,计数资料的比较采用χ2检验;计量资料经Kolmogorov-Smirnov检验不符合正态性及方差齐性,以中位数(四分位数)表示,采用Kruskal-Wallis H检验进行比较,对于有统计学差异的指标进一步采用秩和检验进行组间两两比较,并采用Bonferroni校正后的结果。应用χ2检验分析FABP2 rs1799883 基因型分布是否符合Hardy-Weinberg遗传平衡定律,以避免数据不具备群体代表性。采用χ2检验分析4组FABP2 rs1799883基因型分布和等位基因频率的差异。采用非条件Logistic回归模型分析基因型和等位基因与患病风险的关系,计算比值比(OR)及95%可信区间(95%CI)。P<0.05则认为差异具有统计学意义。
2 结 果
2.1 各组一般临床资料比较
NAFLD组的BMI、ALT、TC高于对照组,差异有统计学意义(Z=3.219~6.277,P<0.05);CAD组的年龄、ALT、FPG高于对照组,而HDL、LDL低于对照组,差异有统计学意义(χ2=32.345,Z=3.192~6.730,P<0.05);合并组的年龄、ALT、TG、FPG高于对照组,而TC、HDL、LDL低于对照组,差异有统计学意义(χ2=32.345,Z=2.869~5.323,P<0.05);合并组的年龄、TG、FPG高于NAFLD组,而TC、HDL、LDL低于NAFLD组,差异有统计学意义(χ2=32.345,Z=3.369~11.237,P<0.05)。见表1。 2.2 各组FABP2 rs1799883基因型分布和等位基因频率的比较
本文4组研究对象基因型分布均符合Hardy-Weinberg遗传平衡定律(χ2=0.277~1.112,P>0.05),说明群体的基因分布具有代表性。FABP2 rs1799883的基因型分布在NAFLD组与对照组、合并组与对照组、合并组与NAFLD组间差异均无统计学意义,而在CAD组与对照组间差异有统计学意义(χ2=6.495,P<0.05)。4组人群FABP2 rs1799883等位基因频率比较差异均无统计学意义(P>0.05)。见表2。
2.3 FABP2 rs1799883基因型分布和等位基因频率与NAFLD和CAD发病风险的相关性
非条件Logistic回归模型分析显示,FABP2 rs1799883 CT+TT基因型与CAD的发病风险显著相关,该基因型是CAD的一种保护因素(OR=0.50,95%CI=0.29~0.87,P<0.05);而CT+TT基因型与NAFLD或NAFLD合并CAD的发病风险均无相关性。考虑到年龄是CAD及NAFLD發病危险因素,且CAD发病男性早于女性,FABP2基因表达受性别调控[20],本文对性别、年龄进行了校正。校正后,CT+TT基因型仍然与CAD发病风险相关(OR=0.46,95%CI=0.24~0.90,P<0.05)。见表3。
3 讨 论
NAFLD是与遗传、环境、代谢、应激等多种因素相关的疾病。有研究证实,遗传因素在NAFLD的发病机制中扮演十分重要的角色[21]。FABP2 rs1799883基因多态性与胰岛素抵抗和血脂代谢异常显著相关,而胰岛素抵抗和血脂代谢异常也均是NAFLD和CAD的独立危险因素。本研究首次探讨了我国青岛汉族人群中FABP2 rs1799883基因多态性与NAFLD和CAD易感性的相关性。
FABP2 rs1799883基因的基因型分布在不同国家和地区具有差异性。FABP2 rs1799883 T等位基因在许多国家和地区的研究中被发现是高脂血症的危险因素。有研究结果显示,在南印度人群中FABP2 rs1799883基因野生型是AA基因型,突变型是AT、TT基因型,AT、TT基因型血TG水平高于AA基因型,提示T等位基因可能是血脂水平的危险因素[22]。加拿大一项研究结果显示,FABP2 rs1799883的等位基因是A和T,T等位基因与新酯化TG分泌增加、载脂蛋白B合成增加以及乳糜微粒产量增加有关[23]。中国南京地区的一项研究结果表明,FABP2 rs1799883为AT、TT基因型的个体比AA基因型个体有更高的TG、TC水平和更低的HDL-C水平[24]。而血脂水平是NAFLD和CAD两种疾病的危险因素。所以我们推测FABP2 rs1799883 T等位基因可能是NAFLD和CAD的危险因素。中国福建地区的一项研究结果也表明,FABP2 rs1799883 TT基因型与NAFLD明显相关,是其独立危险因素[16]。
但克罗地亚的一项纳入140名老年男性和176名老年女性的研究结果显示,FABP2 rs1799883 T等位基因携带者相较非携带者有更高的HDL-C水平和更低的TG水平[25]。新疆维吾尔族的一项研究显示,FABP2 rs1799883 等位基因同样是C和T,但并未发现其和NAFLD的关联[26]。本研究也未显示FABP2 rs1799883基因多态性与NAFLD的相关性。但本研究结果显示,FABP2 rs1799883 CT+TT基因型与CAD的发病风险显著相关,是CAD的一种保护性因素。这与诸多研究结论相反,但与克罗地亚的研究结果相符[25]。考虑到青岛地区FABP2 rs1799883等位基因是C和T,与大多数国家和地区都不同,结果不一致可能是由于地域、种族不同所致。本研究中,FABP2 rs1799883 CT+TT基因型虽然与CAD的发病风险显著相关,但却与CAD合并NAFLD发病风险不相关。分析原因,可能FABP2 rs1799883在NAFLD与CAD的发病过程中存在不同的效应,相互有所抵消,也不除外实验误差所致。本研究的不足之处:仅在基因水平上进行了研究,未对基因表达产物进行深入探讨和分析;此次研究受地域条件、受试者数量等所限,可能影响结果的准确性。
总之,本研究首次探讨了FABP2 rs1799883基因多态性与中国青岛汉族人群NAFLD和CAD发病风险的相关性,结果表明中国青岛地区FABP2 rs1799883的基因型与中国南方地区以及国外大部分国家和地区不同,且其CT+TT基因型与CAD的发病风险相关,而与NAFLD的发病风险不相关,具体作用机制仍待进一步研究。
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(本文编辑 马伟平)
[关键词] 脂肪酸结合蛋白质类;多态性,单核苷酸;非乙醇性脂肪性肝病;冠心病;青岛
[中图分类号] R575.5;R541.4 [文献标志码] A [文章编号] 2096-5532(2020)05-0549-05
doi:10.11712/jms.2096-5532.2020.56.171 [开放科学(资源服务)标识码(OSID)]
[ABSTRACT] Objective To investigate the association of FABP2 rs1799883 gene polymorphism with nonalcoholic fatty liver disease (NAFLD) and coronary artery disease (CAD) in the Chinese Han population in Qingdao, China. Methods A total of 296 inpatients admitted to Qingdao Municipal Hospital were included and divided into NAFLD group, CAD group, and NAFLD with CAD group. Another 104 healthy individuals who underwent physical examination were included as control group. After collection of clinical information, PCR and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry were used to determine the genotype of FABP2 rs1799883. The unconditional Logistic regression model was used to analyze the relationship of genotype and allele with disease risk. Results The genotype distribution of FABP2 rs1799883 was not significantly different between the NAFLD group and the control group, between the NAFLD with CAD group and the control group, and between the NAFLD with CAD group and the NAFLD group, but was significantly different between the CAD group and the control group (χ2=6.495,P<0.05). The allele frequency of FABP2 rs1799883 showed no significant difference between the four groups (P>0.05). The logistic regression analysis showed that FABP2 rs1799883 CT+TT genotype was significantly associated with the risk of CAD and was a protective factor against CAD (OR=0.50,95%CI=0.29-0.87,P<0.05). After adjustment for sex and age, CT+TT genotype was still associated with the risk of CAD (OR=0.46,95%CI=0.24-0.90,P<0.05). Conclusion Among the Chinese Han population in Qingdao, the FABP2 rs1799883 gene polymorphism is not significantly associated with the risk of NAFLD or NAFLD with CAD, but its CT+TT genotype is associated with the risk of CAD and is a protective factor against CAD. [KEY WORDS] fatty acid-binding proteins; polymorphism, single nucleotide; non-alcoholic fatty liver disease; coronary disease; Qingdao
非乙醇性脂肪性肝病(NAFLD)是指除乙醇外,由其他明确肝损伤因素所致的以肝细胞内脂肪过度沉积为主要特征的临床病理综合征。NAFLD的发展呈现一系列病理特征,包括单纯性非乙醇性脂肪肝、非乙醇性脂肪性肝炎、肝纤维化等,最终发展为肝癌[1]。近年来,NAFLD的患病率逐年上升,亚洲NAFLD患病率从2016年的27.4%上升到2019年的29.8%[2-3]。NAFLD的发生发展与2型糖尿病、肥胖等代谢综合征密切相关[3],其影响因素包括炎症、免疫、代谢、脂毒性、纤维化和基因等[4]。冠状动脉粥样硬化性心脏病(CAD)是指因冠状动脉发生管腔内狭窄或闭塞,继而致使心肌缺血或坏死所引起的心脏病。CAD的发病机制尚不完全明确。代谢综合征以及血脂水平的升高与CAD的发病风险明显相关[5]。
FABP2基因屬于FABP基因超家族,主要在小肠上皮细胞中表达,编码为包含132个氨基酸残基的分子量为15 100的肠道脂肪酸结合蛋白。而后者可以选择性结合未酯化的长链脂肪酸及其他配体,负责摄取膳食中的游离脂肪酸[6]。已有多项研究结果表明,FABP2调控人体脂肪代谢,可以促进肠道n-3多不饱和脂肪酸吸收,介导三酰甘油(TG)合成胆固醇[7-9]。FABP2基因多态性还与2型糖尿病相关[10-15]。FABP2与NAFLD、CAD的发病也有相关性。中国福建的一项研究显示,FABP2等位基因为A和T及TT基因型有更高的NAFLD风险[16]。美国的一项研究表明,FABP2 rs1799883 T等位基因携带者有更高的心肌梗死风险[17]。墨西哥的一项研究显示,FABP2 rs1799883 T等位基因携带者比非携带者有更高的心血管疾病风险[18]。在中国,尚无FABP2 rs1799883基因与CAD关系的研究报道。本研究对FABP2 rs1799883基因多态性与青岛汉族人群NAFLD和CAD发病风险的相关性进行探讨,从而为研究NAFLD、CAD的相关遗传发病机制提供新思路,并为将来可能实现的个体化基因治疗铺路。
1 对象与方法
1.1 研究对象
在医院伦理委员会的许可下,选取2018年1月—2019年9月于青岛市市立医院住院的病人296例,其中NAFLD病人90例(NAFLD组,B组)、CAD病人99例(CAD组,C组)、NAFLD合并CAD病人107例(NAFLD合并CAD组,简称合并组,D组);同时纳入104名健康体检者作为对照组(A组)。NAFLD诊断符合《非酒精性脂肪性肝病防治指南》的标准[19]并经B型超声检查证实。CAD经冠状动脉或其分支的冠状动脉造影诊断。同时排除乙醇性肝炎、病毒性和自身免疫性肝炎、药物性肝炎、妊娠急性脂肪肝等其他原因引起的肝脏疾病,以及主动脉夹层、心房颤动、风湿性免疫疾病、心肌病、大动脉炎等其他可能引起CAD的疾病。健康对照均通过生化指标结合超声检查确认。
1.2 标本采集及资料收集
受试者禁饮食12 h后,常规采集静脉血8 mL,分别取4 mL置入A、B两支EDTA抗凝管中。A管用于检测生化指标,包括丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、空腹血糖(FBG)、TG、总胆固醇(TC)、高密度脂蛋白(HDL)以及低密度脂蛋白(LDL)等。B管离心后置于-80 ℃冰箱中保存备用。使用标准问卷调查研究对象姓名、性别、年龄等基本信息,用专业仪表测量身高和体质量,并计算体质量指数(BMI)。
1.3 全血基因组DNA的提取和检测
应用血液基因组DNA提取试剂盒(北京博淼生物科技有限公司)提取全血基因组DNA。采用聚合酶链反应(PCR)方法检测FABP2基因rs179983位点多态性。所用的PCR引物由北京博淼生物科技有限公司设计合成,序列如下:上游引物5′-ACG-TTGGATGGCTGACAATTACACAAGAAGG-3′,下游引物5′-ACGTTGGATGGGTGACACCAAG-TTCAAAAAC-3′。PCR扩增反应后,将PCR产物用虾碱性磷酸酶(SAP)处理,之后进行单碱基延伸反应、树脂纯化及芯片点样。最后进行质谱检测分析基因型。
1.4 统计学方法
使用SPSS 21.0(Windows 10)软件进行统计学分析。4组一般临床资料比较时,计数资料的比较采用χ2检验;计量资料经Kolmogorov-Smirnov检验不符合正态性及方差齐性,以中位数(四分位数)表示,采用Kruskal-Wallis H检验进行比较,对于有统计学差异的指标进一步采用秩和检验进行组间两两比较,并采用Bonferroni校正后的结果。应用χ2检验分析FABP2 rs1799883 基因型分布是否符合Hardy-Weinberg遗传平衡定律,以避免数据不具备群体代表性。采用χ2检验分析4组FABP2 rs1799883基因型分布和等位基因频率的差异。采用非条件Logistic回归模型分析基因型和等位基因与患病风险的关系,计算比值比(OR)及95%可信区间(95%CI)。P<0.05则认为差异具有统计学意义。
2 结 果
2.1 各组一般临床资料比较
NAFLD组的BMI、ALT、TC高于对照组,差异有统计学意义(Z=3.219~6.277,P<0.05);CAD组的年龄、ALT、FPG高于对照组,而HDL、LDL低于对照组,差异有统计学意义(χ2=32.345,Z=3.192~6.730,P<0.05);合并组的年龄、ALT、TG、FPG高于对照组,而TC、HDL、LDL低于对照组,差异有统计学意义(χ2=32.345,Z=2.869~5.323,P<0.05);合并组的年龄、TG、FPG高于NAFLD组,而TC、HDL、LDL低于NAFLD组,差异有统计学意义(χ2=32.345,Z=3.369~11.237,P<0.05)。见表1。 2.2 各组FABP2 rs1799883基因型分布和等位基因频率的比较
本文4组研究对象基因型分布均符合Hardy-Weinberg遗传平衡定律(χ2=0.277~1.112,P>0.05),说明群体的基因分布具有代表性。FABP2 rs1799883的基因型分布在NAFLD组与对照组、合并组与对照组、合并组与NAFLD组间差异均无统计学意义,而在CAD组与对照组间差异有统计学意义(χ2=6.495,P<0.05)。4组人群FABP2 rs1799883等位基因频率比较差异均无统计学意义(P>0.05)。见表2。
2.3 FABP2 rs1799883基因型分布和等位基因频率与NAFLD和CAD发病风险的相关性
非条件Logistic回归模型分析显示,FABP2 rs1799883 CT+TT基因型与CAD的发病风险显著相关,该基因型是CAD的一种保护因素(OR=0.50,95%CI=0.29~0.87,P<0.05);而CT+TT基因型与NAFLD或NAFLD合并CAD的发病风险均无相关性。考虑到年龄是CAD及NAFLD發病危险因素,且CAD发病男性早于女性,FABP2基因表达受性别调控[20],本文对性别、年龄进行了校正。校正后,CT+TT基因型仍然与CAD发病风险相关(OR=0.46,95%CI=0.24~0.90,P<0.05)。见表3。
3 讨 论
NAFLD是与遗传、环境、代谢、应激等多种因素相关的疾病。有研究证实,遗传因素在NAFLD的发病机制中扮演十分重要的角色[21]。FABP2 rs1799883基因多态性与胰岛素抵抗和血脂代谢异常显著相关,而胰岛素抵抗和血脂代谢异常也均是NAFLD和CAD的独立危险因素。本研究首次探讨了我国青岛汉族人群中FABP2 rs1799883基因多态性与NAFLD和CAD易感性的相关性。
FABP2 rs1799883基因的基因型分布在不同国家和地区具有差异性。FABP2 rs1799883 T等位基因在许多国家和地区的研究中被发现是高脂血症的危险因素。有研究结果显示,在南印度人群中FABP2 rs1799883基因野生型是AA基因型,突变型是AT、TT基因型,AT、TT基因型血TG水平高于AA基因型,提示T等位基因可能是血脂水平的危险因素[22]。加拿大一项研究结果显示,FABP2 rs1799883的等位基因是A和T,T等位基因与新酯化TG分泌增加、载脂蛋白B合成增加以及乳糜微粒产量增加有关[23]。中国南京地区的一项研究结果表明,FABP2 rs1799883为AT、TT基因型的个体比AA基因型个体有更高的TG、TC水平和更低的HDL-C水平[24]。而血脂水平是NAFLD和CAD两种疾病的危险因素。所以我们推测FABP2 rs1799883 T等位基因可能是NAFLD和CAD的危险因素。中国福建地区的一项研究结果也表明,FABP2 rs1799883 TT基因型与NAFLD明显相关,是其独立危险因素[16]。
但克罗地亚的一项纳入140名老年男性和176名老年女性的研究结果显示,FABP2 rs1799883 T等位基因携带者相较非携带者有更高的HDL-C水平和更低的TG水平[25]。新疆维吾尔族的一项研究显示,FABP2 rs1799883 等位基因同样是C和T,但并未发现其和NAFLD的关联[26]。本研究也未显示FABP2 rs1799883基因多态性与NAFLD的相关性。但本研究结果显示,FABP2 rs1799883 CT+TT基因型与CAD的发病风险显著相关,是CAD的一种保护性因素。这与诸多研究结论相反,但与克罗地亚的研究结果相符[25]。考虑到青岛地区FABP2 rs1799883等位基因是C和T,与大多数国家和地区都不同,结果不一致可能是由于地域、种族不同所致。本研究中,FABP2 rs1799883 CT+TT基因型虽然与CAD的发病风险显著相关,但却与CAD合并NAFLD发病风险不相关。分析原因,可能FABP2 rs1799883在NAFLD与CAD的发病过程中存在不同的效应,相互有所抵消,也不除外实验误差所致。本研究的不足之处:仅在基因水平上进行了研究,未对基因表达产物进行深入探讨和分析;此次研究受地域条件、受试者数量等所限,可能影响结果的准确性。
总之,本研究首次探讨了FABP2 rs1799883基因多态性与中国青岛汉族人群NAFLD和CAD发病风险的相关性,结果表明中国青岛地区FABP2 rs1799883的基因型与中国南方地区以及国外大部分国家和地区不同,且其CT+TT基因型与CAD的发病风险相关,而与NAFLD的发病风险不相关,具体作用机制仍待进一步研究。
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(本文编辑 马伟平)