外周血白细胞计数对肥胖者发生代谢综合征的预测价值

目的:探讨正常范围内外周血白细胞计数(peripheral white blood cell counts,WBCC)对肥胖者发生代谢综合征(metabolic syndrome,MS)的预测价值.方法:收集湖南省人民医院体检中心2006年4月～2010年1月体检人群共4067例,排除资料不全者,共2830例纳入研究.其中1367例于l～3年后再次来我院体检.肥胖诊断标准按照2000年国际肥胖工作组规定的亚太地区肥胖标准,其中共有肥胖者1120例.代谢综合征诊断标准采用2004年中华医学会糖尿病学分会关于MS的定义.将325例WBCC正常的肥胖者进行四分位数分组(Q1～Q4),随访1～3年后,比较不同WBCC组别发生MS的风险.结果:1.在1120例肥胖体检人群中,肥胖伴MS者352例,占31.43％.2.325例WBCC正常的肥胖者进行四分位数分组(QI～Q4),随访1～3年后,Q4组发生MS的风险明显增高(25.32％ vs 11.11％,OR=2.712;95％ CI:1.149-6.400,P＜0.05).结论:1).肥胖人群中,肥胖伴MS者占31.43％.2).正常范围内WBCC的升高可预测肥胖者MS的发生.     

中国汉族人群PNPLA3 I148M 多态性影响脂联素水平及非酒精性脂肪性 肝病遗传易感性的相关性研究*

目的:探讨在中国人群中PNPLA3 I148M基因型、脂联素与非酒精性脂肪性肝病的遗传易感性的相关性,及PNPLA3基因型与空腹血清脂联素水平的关系。方法:对96例NAFLD患者和76名正常对照,采用多聚酶链反应(PCR)及直接测序法检测PNPLA3基因型。计量资料结果均用均数±标准差(X±S)表示,经方差齐性检验后,行t检验;性别、基因型及等位基因频率的比较行X2检验。结果:中国汉族人群中,存在PNPLA3基因I148M多态性,I148M G等位基因频率分布在NAFLD(64.89%)与正常对照组(34.87%)、NASH组(71.70%)与SS组(56.09%)中比较差异均有统计学意义(P<0.05)。病例对照分析显示:148GG基因携带者与148CC基因携带者相比较,前者发生NAFLD的比值比(OR)为3.45(95%CI:2.21~5.41,P<0.05),发生NASH的OR为1.98(95%CI=1.08~3.64,P<0.05)。PNPLA3基因rs738409多态性与血清ALT水平有关(P<0.05),对NASH组分层分析,148GG基因型BMI、ALT、FINS均高于148CC基因型(P<0.05),血清HDL水平低于148CC基因型和148GC基因型(P<0.05),这些结果提示等位基因G与肝脏炎症和肝脏脂肪增加有相关性.Ordinal Logistic回归分析显示PNPLA3 I148M多态性与低浓度血清脂联素水平相关(<6μg/ml)(OR=2.78,95%CI=1.765~4.384,P<0.05)。结论:中国汉族人群中,PNPLA3基因I148M多态性与NAFLD的遗传易感性及脂联素的分泌调节相关,是决定NAFLD个体遗传易感性的重要因素。     

人染色体8p11(CHRNB3-CHRNA6)区域基因多态性与中国汉族人群肺癌易感性的相关性

为探讨人染色体8p11(CHRNB3-CHRNA6)区域基因多态性与中国汉族人群肺癌遗传易感性之间的关系,文章采用病例-对照研究,对784例肺癌患者和782例性别、年龄、籍贯频数与之相匹配的健康对照中该区域6个标签SNP位点进行基因分型,并统计分析其基因型频率分布与肺癌易感性的关系,以及吸烟在其中的影响。结果发现rs16891561位点TT基因型在60岁以上人群(校正OR=0.42,95%CI=0.20-0.88;P=0.022)、女性人群(校正OR=0.34,95%CI=0.13-0.87;P=0.025)、非吸烟人群中(校正OR=0.32,95%CI=0.13-0.79;P=0.013)对肺癌发生具有保护效应;rs4236926位点TT基因型在60岁以上人群(校正OR=0.48,95%CI=0.23-0.99;P=0.048)、非吸烟人群(校正OR=0.32,95%CI=0.13-0.80;P=0.014)中对肺癌发生具有保护效应,这两种保护效应主要是与腺癌相关。对这两个位点进行累积效应分析发现,含有3~4个变异等位基因型的非吸烟者罹患肺癌的风险显著降低(校正OR=0.29,95%CI=0.11-0.71;P=0.007),并且,含有3~4个变异等位基因型的个体累计吸烟量("包-年"平均数=13.2)与其他个体相比显著降低。由此可见人染色体8p11(CHRNB3-CHRNA6)区域基因多态性与中国汉族人群肺癌易感性和吸烟行为相关。     

新诊断标准下妊娠期糖尿病高危因素研究

目的:调查新诊断标准下国内妊娠期糖尿病(Gestational diabetes mellitus GDM)的发病情况,分析影响GDM发生的高危因素,为新标准下国内GDM孕妇临床早期管理、诊断和干预提供理论依据。方法:对2011年1月至2011年9月我院接受产前建卡检查的所有孕妇1152例进行临床资料的收集及回顾性研究,排除孕前糖尿病患者16例,采用GDM诊断新标准进行"一步法"诊断,收集包括年龄、孕产次、体质指数(body mass index BMI)、糖尿病家族史、多囊卵巢综合征等13种影响GDM发生的危险因素,并综合分析。结果:新标准下GDM检出率为10.39%(118/1136)2)单因素分析结果发现年龄≥35岁(X2=10.2814,P=0.0013)、肥胖(孕前BMI≥28kg/m2()X2=36.2384,P<0.0001)、多囊卵巢综合征(X2=20.6725,P<0.0001)、糖尿病家族史(X2=7.8783,P=0.0050)在GDM组与非GDM组有统计学差异,多因素逐步Logistic回归分析肥胖(OR=7.546 95%CI=2.356~20.129 P=0.0002)、多囊卵巢综合征(OR=6.342 95%CI=1.783~16.329,P=0.0019)、年龄(OR=3.021 95%CI=0.983~6.459 P=0.0108)、糖尿病家族史(OR=2.43895%CI=0.612~5.231 P=0.0256)为GDM的高危因素。结论:新标准下报告GDM检出率为10.39%。肥胖、多囊卵巢综合征、年龄、糖尿病家族史为影响GDM发生的高危因素。加强GDM筛查并对具有高危因素的妊娠期妇女早期诊断,早期干预、早期管理可改善妊娠结局,提高人口素质。     

儿童重型流行性乙型脑炎影响因素分析

目的通过对2010—2016年重庆市渝中区儿童重型流行性乙型脑炎(简称乙脑)影响因素的分析,为该地区儿童重型乙脑的防控提供科学依据。方法采用描述性流行病学方法对重庆市渝中区2010—2016年的儿童乙脑患者的基本特征、分型及其差异性、乙脑病情影响因素进行分析。采用SPSS 20.0软件对乙脑发病特征差异性进行统计学分析,用多因素逐步logistic回归分析儿童重型乙脑的影响因素。结果重庆市渝中区在此期间共报告儿童乙脑病例725例,主要为幼托儿童,其中重型344例(47.45%)。人群分布、诊断型别、是否住院、发病前25 d是否有外出史、头痛、精神萎靡、烦躁、意识障碍、抽搐、脑膜刺激征、病理反射肌张力增强等18个因素在非重型组与重型组间差异均有统计学意义(P0.05);出现惊厥(P0.000 1,OR:2.876～8.237)、意识障碍(P=0.013,OR:1.109～2.436)、脑膜刺激征(P=0.000 5,OR:1.350～2.963)、病理反射肌张力增强(P=0.000 4,OR:1.377～3.023)的乙脑患儿更易发展为重型乙脑。结论儿童重型乙脑病情重、发展较快,因此临床医生在接诊儿童乙脑患者时应注意观察患者惊厥、意识障碍等症状,避免轻型乙脑患者发展为重型。     

MICA基因多态性与海南人群HBV易感关联性研究

研究MICA等位基因多态性与海南人群HBV感染易感性之间的关联性。采用PCR-SSP和PCR-SBT方法对样本MICA等位基因的多态性进行检测。HBV感染患者中共检出10种MICA等位基因和5种MICA-STR等位基因,和对照组相比较,MICA*010、MICA-A5等位基因可能对HBV感染易感(MICA*010:OR=3. 88,95%CI:2. 19～6. 85,P=0. 000; MICA-A5:OR=1. 27,95%CI:0. 92～1. 77,P=0. 0068)。MICA*008/045基因型可能对HBV感染不易感,MICA*010/010纯合子基因型可能对HBV易感(MICA*008/045:OR=0. 09,95%CI:0. 01～1. 74,P=0. 0071; MICA*010/010:OR=4. 41,95%CI:1. 26～15. 46,P=0. 0106)。MICA等位基因多态性与海南人群HBV感染的易感性间存在关联性。     

11q21区段与中国汉族人群Graves病相关性研究

目的:在中国人群中验证Cooper团队在欧洲人群中鉴定的新的Graves病(Graves'disease,GD)易感区段11q21与中国汉族人群GD的相关性。方法:在前期1442例GD患者和1468例正常对照的GWAS数据基础上通过11q21区段精细定位选取主效位点,利用Taqman探针技术进行等位基因分析,在1594例GD患者和1679例正常对照中进行扩大样本验证,然后将两个阶段的结果合并分析并得出11q21区段与GD的相关性结果。结果:验证阶段11q21的rs12575636与GD相关的P值为2.98×10~(-5)(OR=1.42,95%CI=1.20-1.67),GWAS阶段和验证阶段合并后11q21的rs12575636与GD相关的P值达到1.26×10~(-6)(OR=1.35,95%CI=1.19-1.51)。结论:11q21的rs12575636与中国汉族人群GD显著相关,11q21的rs12575636是中国汉族人GD的易感位点。     

CYP1A1、CYP1B1、NET、DAT1单个和联合基因型与汉族人群乳腺癌易感性的研究（英文）

乳腺癌是最常见的女性癌症,其发生是遗传因素和环境因素相互作用的结果。因此,我们就CYP1A1MspⅠ(m1多态)、CYP1B1 Leu432Val、NET T-182C、DAT1-VNTR等基因多态性对新疆汉族人群乳腺癌易感性的研究进行探讨。在以144例乳腺癌患者和120例正常对照组为研究对象的病例-对照研究中,发现CYP1A1MspⅠ位点CC基因型、C等位基因(OR=3.32,95%CI:1.24~8.86;OR=1.58,95%CI:1.09~2.31)和高风险联合基因型CYP1A1 MspⅠ与CYP1B1 Leu432Val,CYP1A1 MspⅠ与DAT1-VNTR,CYP1B1 Leu432Val与DAT1-VNTR(OR=2.43,95%CI:1.23~4.78;OR=4.53,95%CI:1.26~16.27;OR=2.98,95%CI:1.10~8.06)与乳腺癌风险增加有关。CYP1B1、NET和DAT1基因多态性与乳腺癌易感性无关。这些研究结果表明,CYP1A1 MspⅠ多态性和CYP1A1、CYP1B1、DAT1高风险联合基因型能增加新疆汉族人群患乳腺癌的风险。     

血清IL-37、IL-18、NF-κB与非酒精性脂肪性肝病合并幽门螺杆菌感染的相关性

目的探讨血清白介素-23(IL-23)、白介素-18(IL-18)、核因子-κB(NF-κB)与非酒精性脂肪性肝病(NAFLD)合并幽门螺杆菌(H.pylori)感染的相关性。方法选取2013年10月至2019年10月我院收治的83例NAFLD患者作为研究对象,根据是否合并H.pylori感染分为NAFLD+Hp(+)组(n=34)和NAFLD+Hp(-)组(n=49)。选取同期到我院进行体检的100例健康者为对照组。比较3组对象基本资料及血清IL-37、IL-18、NF-κB水平,并进行Pearson相关性分析和Logistic多元回归分析。结果 NAFLD+Hp(+)组和NAFLD+Hp(-)组患者BMI、SBP、DBP、TC、TG、LDL-C、FPG、UA、ALT、AST、ALP、GGT、IL-37、IL-18、NF-κB水平均高于对照组(均P0.05)。NAFLD+Hp(+)组患者TC、TG、LDL-C、FPG、ALT、AST、IL-37、IL-18、NF-κB水平均高于NAFLD+Hp(-)组(均P0.05)。Pearson相关性分析显示,NAFLD患者TG、LDL-C、FPG、IL-37、IL-18、NF-κB水平及H.pylori感染情况与肝功能指标(ALT、AST)均呈正相关,同时TG、LDL-C、FPG、IL-37、IL-18、NF-κB水平与H.pylori感染情况也均呈正相关(均P0.05)。Logistic多元回归分析显示,TG、LDL-C、FPG、ALT、IL-37、IL-18、NF-κB是NAFLD患者合并H.pylori感染的危险因素。结论 IL-37、IL-18、NF-κB与NAFLD患者合并H.pylori感染有关,且H.pylori感染会引起患者脂质、糖代谢紊乱。     

外科ICU 中心静脉导管相关血流感染的回顾性病例对照研究

目的:了解外科ICU中心静脉导管相关血流感染(CRBSI)的发病率、病原菌分布及相关危险因素,为临床预防和经验性治疗提供依据。方法:回顾性调查我院外科ICU 2010年1月～2011年8月的中心静脉导管置管病例,根据血培养和导管培养结果分为CRBSI组和非CRBSI组,统计CRBSI的发病率、致病菌;比较CRBSI组与非CRBSI的临床资料,应用多因素Logistic回归分析筛查相关危险因素。结果:共收集249例中心静脉置管病例,CRBSI发病率为8.41例次/千导管日,病原菌分布为G+菌4例,G-菌9例,真菌8例。Logistic回归分析显示导管留置时间(OR 3.298,95%CI 1.070~10.168,P=0.038)、APACHEII评分(OR 1.137,95%CI 1.067~1.213,P=0.000)、完全胃肠外营养(OR 1.117,95%CI 1.023~1.219,P=0.014)是CRBSI的独立危险因素。结论:导管留置时间、APACHEII评分、完全胃肠外营养是发生CRBSI的独立危险因素。     

Two genetic variants in FABP1 and susceptibility to non-alcohol fatty liver disease in a Chinese population

Liver fatty acid-binding protein (FABP1) serves as a key regulator of hepatic lipid metabolism, and polymorphisms within the FABP1 gene have been associated with several metabolic traits. To investigate the association between FABP1 polymorphisms and the risk of non-alcohol fatty liver disease (NAFLD) in a Chinese population, the genotypes and haplotypes of FABP1 (rs2241883 T/C and rs1545224G/A) were determined in 553 patients with NAFLD and 553 healthy controls. The results showed that individuals with at least one copy of the rs2241883 C allele (TC or CC genotype) had an elevated risk for developing NAFLD (odds ratio [OR]=1.32, 95% CI: 1.01-1.71), and individuals with at least one copy of the rs1545224 A allele (GA or AA genotype) also had a significantly increased risk for NAFLD (OR=1.52, 95% CI: 1.14-2.02). Cumulative effect analysis of the two SNPs revealed that individuals with two risk genotypes were at significantly higher risk of NAFLD than those without risk genotype, and a significant trend of increased risk with increasing numbers of risk genotype was observed. Stratification analysis showed that the rs2241883 C allele carriers had higher level of LDL-C and the rs1545224 A allele carriers had higher level of FPG than those without this allele. In addition, haplotype analysis revealed that the one composed of the rs1545224 A and rs2241883 C variants was significantly associated with an increased risk for NAFLD (OR=1.34; 95% CI=1.05-1.40) compared to the GT haplotype. Taken together, the present study suggests that genetic variations within FABP1 influence susceptibility to NAFLD independently or jointly.     

不同亚型脂联素与非酒精性脂肪性肝病的关系

目的:探究总脂联素(total adiponectin,total APN)和高分子量脂联素(high-molecular-weight adiponectin,HMW APN)与非酒精性脂肪性肝病(Nonalcoholic Fatty Liver Disease,NAFLD)的关系。方法:连续纳入50名男性健康男性及50名非酒精性脂肪性肝病男性患者,收集患者临床资料及其他临床生化数据,通过ELISA法检测总脂联素、支链氨基酸及可溶性晚期糖基化终末产物含量,Western blot法测定高分子量、中分子量和低分子量脂联素水平,进一步分析其相关性。结果:与对照组的健康受试者相比,NAFLD患者的总脂联素和三种不同形式的脂联素水平均显著降低。在NAFLD患者中,总脂联素与身高(R=-0.270, P=0.032)和羧甲基赖氨酸(R=-0.259, P=0.040)显著负相关;高分子量脂联素与空腹血糖(R=0.350, P=0.016)显著正相关,与丙氨酸氨基转移酶(R=-0.321, P=0.029)和天门冬氨酸氨基转移酶(R=-0.295, P=0.045)显著负相关。结论:总脂联素和三种不同形式的脂联素水平均与NAFLD呈显著负相关。     

Defining Metabolically Healthy Obesity: Role of Dietary and Lifestyle Factors

Background

There is a current lack of consensus on defining metabolically healthy obesity (MHO). Limited data on dietary and lifestyle factors and MHO exist. The aim of this study is to compare the prevalence, dietary factors and lifestyle behaviours of metabolically healthy and unhealthy obese and non-obese subjects according to different metabolic health criteria.

Method

Cross-sectional sample of 1,008 men and 1,039 women aged 45-74 years participated in the study. Participants were classified as obese (BMI ≥30kg/m²) and non-obese (BMI <30kg/m²). Metabolic health status was defined using five existing MH definitions based on a range of cardiometabolic abnormalities. Dietary composition and quality, food pyramid servings, physical activity, alcohol and smoking behaviours were examined.

Results

The prevalence of MHO varied considerably between definitions (2.2% to 11.9%), was higher among females and generally increased with age. Agreement between MHO classifications was poor. Among the obese, prevalence of MH was 6.8% to 36.6%. Among the non-obese, prevalence of metabolically unhealthy subjects was 21.8% to 87%. Calorie intake, dietary macronutrient composition, physical activity, alcohol and smoking behaviours were similar between the metabolically healthy and unhealthy regardless of BMI. Greater compliance with food pyramid recommendations and higher dietary quality were positively associated with metabolic health in obese (OR 1.45-1.53 unadjusted model) and non-obese subjects (OR 1.37-1.39 unadjusted model), respectively. Physical activity was associated with MHO defined by insulin resistance (OR 1.87, 95% CI 1.19-2.92, p = 0.006).

Conclusion

A standard MHO definition is required. Moderate and high levels of physical activity and compliance with food pyramid recommendations increase the likelihood of MHO. Stratification of obese individuals based on their metabolic health phenotype may be important in ascertaining the appropriate therapeutic or intervention strategy.     

Methylenetetrahydrofolate reductase gene polymorphisms in patients with nonalcoholic steatohepatitis (NASH)

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of abnormal hepatic steatosis in the absence of a history of alcohol use. Nonalcoholic steatohepatitis (NASH) is the progressive form of NAFLD. Hyperhomocysteinemia causes steatosis, and the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms result in hyperhomocysteinemia. To examine whether the C677T and A1298C polymorphisms of the MTHFR gene were associated with NASH, we analysed the allele and genotype distribution of the MTHFR C677T and A1298C polymorphisms in 57 well-diagnosed NASH patients, 324 healthy controls in a case-control study of Turkish subjects of Caucasian origin. The diagnosis of the NASH patients was based on liver biopsy. The method used in the analysis of genotypes was PCR-RFLP. The MTHFR A1298C polymorphism was significantly associated with NASH (chi(2) = 8.439; p = 0.015) in the total NASH patients compared with healthy controls. The MTHFR 1298C allele (odds ratio (OR) = 2.480; 95%CI = 1.286-4.782; chi(2) = 7.703; df = 1; p = 0.006) was significantly associated with NASH in the total NASH patients. The MTHFR C677C/A1298C compound genotype (OR = 2.218; 95%CI = 1.003-4.906; chi(2) = 3.998; df = 1; p = 0.046) in men patients was also significantly associated with NASH. Likewise the MTHFR C1298C genotype was significantly associated with NASH in women patients with NASH (OR = 2.979; 95%CI = 1.027-8.641; chi(2) = 4.343; df = 1; p = 0.037). In conclusion, the MTHFR 1298C allele in all NASH patients, C1298C genotype, C677C/C1298C compound genotype in women NASH patients and C677C/A1298C compound genotype in men NASH patients were genetic risk factors for NASH.     

Plasma levels of plant sterols and the risk of coronary artery disease: the prospective EPIC-Norfolk Population Study

Some studies have suggested that a modest increase of plant sterol levels is a risk factor for coronary artery disease (CAD). We studied the relationship between plant sterol levels and CAD risk in a prospective nested case-control study consisting of 373 cases and 758 controls. Sitosterol and campesterol concentrations did not differ between cases and controls [sitosterol, 0.21 vs. 0.21 mg/dl (P = 0.1); campesterol, 0.31 vs. 0.32 mg/dl (P = 0.5)]. The sitosterol-to-cholesterol ratio was significantly lower in cases than in controls (1.19 vs. 1.29 microg/mg; P = 0.008), whereas the campesterol-to-cholesterol ratio did not differ significantly (1.78 vs. 1.88 microg/mg; P = 0.1). Plant sterol concentrations correlated positively with cholesterol levels and inversely with body mass index and triglyceride and lathosterol concentrations. Among individuals in the highest tertile of the sitosterol concentration, the unadjusted odds ratio (OR) for future CAD was 0.75 [95% confidence interval (CI) = 0.56-1.01]. After adjustment for traditional risk factors, the OR was 0.79 (95% CI = 0.56-1.13). For the campesterol concentration, the unadjusted OR was 0.95 (95% CI = 0.71-1.29) and the adjusted OR was 0.97 (95% CI = 0.68-1.39). In this large prospective study, higher levels of plant sterols, at least in the physiological range, do not appear to be adversely related to CAD in apparently healthy individuals.     

人巨细胞病毒IE1-72蛋白在胶质瘤中的表达及意义

目的:探讨人巨细胞病毒(HCMV)立刻早期基因1-72(IE1-72)蛋白在胶质瘤中的表达水平以及HCMV感染与胶质瘤发生的病因学关系。方法:采用免疫组化方法检测HCMV IE1-72蛋白在125例人脑胶质瘤组织及10例正常人脑组织中的表达,分析其表达水平与胶质瘤临床病理学特征的关系。结果:IE1-72蛋白在胶质瘤组织中的表达水平明显高于正常人脑组织(P=0.000);IE1-72蛋白免疫染色强度随胶质瘤病理级别的升高而明显增强(r=0.310,P=0.000),其在高恶性度胶质瘤中的染色强度明显强于低恶性度胶质瘤(P=0.004);IE1-72蛋白染色强度与胶质瘤患者的年龄存在正相关(r=0.234,P=0.009),而与胶质瘤患者的性别(r=0.038,P=0.675)以及肿瘤部位(r=0.086,P=0.341)无明显相关性。结论:HCMV感染及其蛋白IE1-72表达可能与人脑胶质瘤的发生和发展密切相关,但其确切的致瘤机制尚需进一步研究。     

慢性肾脏病并发左室肥厚现况及其危险因素

目的:探索中老年慢性肾脏病并发左室肥厚(LVH)的现况及其危险因素。方法:对我院肾内科住院的40-75岁CKD2-5期患者210例的病历资料进行回顾性分析。结果:(1)心脏舒张功能减退发生率高于收缩功能减退(79.1%VS 20.3%P=0.000);左房扩大检出率高于左室扩大检出率(46.5%VS 19.8%P=0.000);室间隔增厚检出率(IVSH)也高于左室后壁增厚检出率(LVPWH)(43.0%VS 21.1%P=0.000);LVH的发生率高于IVSH检出率(47.9%VS 35%P=0.001),其中女性LVH高于男性(73.2%VS31.0%P=0.000),然而若采用另外一种诊断标准,两者并无统计学差异(50%VS 34.5%P=0.068)。(2)IVSH组收缩压、脉压、血肌酐均高于无IVSH组。IVSH组除上述因素外血磷尚高于无IVSH组,但在CKD5期的亚组分析中仅收缩压与对照组相比有统计学差异。LVH组收缩压、脉压均高于无LVH组,而血红蛋白、体质指数则低于对照组。进一步Logistic回归分析提示仅性别、体质指数有统计学意义。结论:(1)40-75岁的心血管疾病高危的CKD患者中,采用超声心动图诊断LVH,根据公式计算的LVMI诊断阳性率最高,但诊断切点仍需进一步研究。(2)收缩压升高、脉压增大、贫血、低体质指数、女性均可能是LVH的危险因素,控制血压、纠正贫血和营养不良可能是防治LVH的重要靶点。     

The Impact of PNPLA3 rs738409 Genetic Polymorphism and Weight Gain ≥10 kg after Age 20 on Non-Alcoholic Fatty Liver Disease in Non-Obese Japanese Individuals

Non-alcoholic fatty liver disease (NAFLD) in non-obese individuals is inadequately elucidated. We aim to investigate the impact of known genetic polymorphisms on NAFLD and the interaction between genetic risks and weight gain on NAFLD in obese and non-obese Japanese individuals. A total of 1164 participants who received health checkups were included. Participants with excessive alcohol consumption, with viral hepatitis or other inappropriate cases were excluded. Fatty liver was diagnosed by ultrasonography. Participants with a body mass index (BMI) of <18.5 kg/m², 18.5–22.9 kg/m², 23.0–24.9 kg/m² and ≥25 kg/m² were classified underweight, normal weight, overweight and obese, respectively. Self-administered questionnaire for lifestyle was assessed and a total of 8 previously reported genetic polymorphisms were chosen and examined. In all, 824 subjects were enrolled. The overall prevalence of NAFLD was 33.0%: 0% in underweight, 15.3% in normal weight, 41.1% in overweight and 71.7% in obese individuals. The prevalence of NAFLD is more affected by the G allele of patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 in normal weight (odds ratio (OR) 3.52; 95%-CI: 1.42–8.71; P = 0.0063) and in overweight individuals (OR 2.60; 95%-CI: 1.14–5.91; P = 0.0225) than in obese individuals (not significant). Moreover, the G allele of PNPLA3 rs738409 and weight gain ≥10 kg after age 20 had a joint effect on the risk of NAFLD in the normal weight (OR 12.00; 95% CI: 3.71–38.79; P = 3.3×10⁻⁵) and the overweight individuals (OR 13.40; 95% CI: 2.92–61.36; P = 0.0008). The G allele of PNPLA3 rs738409 is a prominent risk factor for NAFLD and the interaction between the PNPLA3 rs738409 and weight gain ≥10 kg after age 20 plays a crucial role in the pathogenesis of NAFLD, especially in non-obese Japanese individuals.     

NT FRZ 基因多态性与SEL 的相关性研究

本研究通过调查中国南方SLE人群和健康对照人群中TNFR2基因两个位点（nt587,nt694）的多态性频率,探讨TNFR2基因多态性是否与中国汉族SLE人群的易感性相关。结果发现128例SLE中,nt587G的等位基因频率为54个（21．1％）;而135例健康人群中nt587G的频率为35个（13．0％）;SLE组明显高于健康对照人群（P〈0．05）,携带nt587G的个体SLE发病危险性大。同时128例SLE中,舶94A的等位基因频率为41个（16．0％）;而健康人群中舶94A的频率为32个（11．9％）;两组比较无显著差异（P=0．149）。提示TNFR2基因nt587的多态性与中国南方SLE人群相关,可能通过影响TNFR2的表达而参与SLE的发病,而nt694（G—A）的多态性与中国南方SLE人群不相关。     

A multi-ethnic study of a PNPLA3 gene variant and its association with disease severity in non-alcoholic fatty liver disease

The adiponutrin (PNPLA3) rs738409 polymorphism has been found to be associated with susceptibility to non-alcoholic fatty liver disease (NAFLD) in various cohorts. We further investigated the association of this polymorphism with non-alcoholic steatohepatitis (NASH) severity and with histological features of NAFLD. A total of 144 biopsy-proven NAFLD patients and 198 controls were genotyped for PNPLA3 gene polymorphism (rs738409 C>G). The biopsy specimens were histologically graded by a qualified pathologist. We observed an association of G allele with susceptibility to NAFLD in the pooled subjects (OR 2.34, 95% CI 1.69-3.24, p < 0.0001), and following stratification, in each of the three ethnic subgroups, namely Chinese, Indian and Malay (OR 1.94, 95% CI 1.12-3.37, p = 0.018; OR 3.51, 95% CI 1.69-7.26, p = 0.001 and OR 2.05, 95% CI 1.25-3.35, p = 0.005, respectively). The G allele is associated with susceptibility to NASH (OR 2.64, 95% CI 1.85-3.75, p < 0.0001), with NASH severity (OR 1.85, 95% CI 1.05-3.26, p = 0.035) and with presence of fibrosis (OR 1.95, 95% CI 1.17-3.26, p = 0.013) but not with simple steatosis nor with other histological parameters. Although the serum triglyceride level is significantly higher in NAFLD patients compared to controls, the G allele is associated with decreased level of triglycerides (p = 0.029) in the NAFLD patients. Overall, the rs738409 G allele is associated with severity of NASH and occurrence of fibrosis in patients with NAFLD.