摘要
目的探讨PNPLA3基因m738409多态性（编码1148M）与非酒精性脂肪性肝病（NAFLD）遗传易感性的相关性。方法对315例NAFLD患者和336名健康体检正常者（对照组），采用多聚酶链反应及基因型检测方法对研究对象进行PNPLA3基因m738409多态性基因型分析。计量资料经方差齐性检验之后，行f检验；性别、基因型及等位基因频率的比较行x2检验。结果（1）m738409基因多态性，经检测得出148CC，148GC，148GG3种基因型。（2）148GG基因型频率分布在NAFLD组为45．1％，对照组为12．5％，两组比较，x2=85．110，P〈0．05。PNPLA3m738409G等位基因频率分布，在NAFLD组是65．4％，对照组是33．2％;非酒精性脂肪性肝炎（NASH）组为71．9％，非酒精性单纯性脂肪肝组为56．5％，两组比较，x2值为135．041和16．210，P〈0．05，差异均有统计学意义。（3）多变量非条件logistic回归分析显示：148GG基因型频率高于对照组，148CC基因型频率低于对照组，携带m738409G等位基因的个体患NAFLD的风险是携带rs738409C等位基因个体的3．81倍（OR=3．81，95％CI=3．03～4．79，P〈0．05），携带m738409G等位基因的单纯脂肪肝个体发生NASH的风险为1．97倍（OR=1．97，95％口=1．41～2．75，P〈0．05）。（4）NASH组中，148GG基因型体质量指数（BMI）为27．4±2．9、ALT为（131．7±40．6）U／L、空腹胰岛素为（9．1±2．6）μU／ml；148CC基因型BMI为27．4±2．9、ALT为（79．6±47．6）U／L、空腹胰岛素为（7．0±1．6）μU／ml，两组比较，F值分别为0．055，3．754和0．626，P值均〈0．05。148GC基因型BMI为28．0±3．2，ALT为（121．0±16．6）U／L，148CC基因型BMI为22．1±2．8，ALT为（9．6±47．6）U／L，两组比较，，值为0．067和4．278，尸值均〈0．05。高密度脂蛋白148GG基因型为（1．2±0．6）mmol／L，148GC基因型为（1．9土1．0）mmol／L，148CC基因型为（2．2±0．9）mmol／L，148GG基因型与148GC基因型和148CC基因型相比，F值为0．641和2．148，P值均〈0．05。结论在汉族人群中，PNPLA3m738409多态性与NAFLD的发生相关，是决定NAFLD个体遗传易感性的重要因素。
Objective To study the relationship between the patatin-like phospholipase domain- containing protein 3 （PNPLA3） gene and hereditary susceptibility to non-alcoholic fatty liver disease （NAFLD） by detecting single nucleotide polymorphisms （SNPs）. Methods Peripheral blood DNA from 315 patients diagnosed with NAFLD （including the spectrum of simple steatosis （SS） and non-alcoholic steatosis （NASH）） and 336 control subjects was used to determine the PNPLA3 genotype by polymerase chain reaction （PCR） and direct sequencing. The relationship of SNPs and NAFLD-related markers of liver function were assessed by correlation analysis. Results The SNP rs738409 was identified in more of the NAFLD patients （allele variant frequencies： NAFLD, 65.40%; NASH： 71.87%; SS, 56.47%） than in the controls （33.18%）. Case-control analysis revealed that carriers of the 148GG genotype were at 3.81-fold （95% CI： 3.03 - 4.79） higher risk of developing NAFLD and at 1.97-fold （95% CI： 1.41 - 2.75） higher risk of progressing from SS to NASH, compared with non-carriers, rs738409 was also found to be associated with serum levels of alanine aminotransferase （ALT） and y-glutamyltransferase （y-GT） （both P 〈 0.05）. Carriers of the 148GG genotype had significantly higher body mass index, ALT, and fasting insulin than carriers of the 148CC genotype （all P 〈 0.05）, and significantly higher level of serum HDL than carriers of either the 148CC genotype or the 148GC genotype （both P 〈 0.05）. Conclusion Polymorphisms in the PNPLA3 gene may play an important role in mediating susceptibility to developing NAFLD in the Chinese population. The rs738409 polymorphism, in particular, is related to development and progression of NAFLD and may play a role in the contribution of PNPLA3 to NAFLD pathogenesis.
出处
《中华肝脏病杂志》
CAS
CSCD
北大核心
2013年第8期619-623,共5页
Chinese Journal of Hepatology
基金
基金项目：国家自然基金（81170337/H0304）
关键词
脂肪肝
基因
基因频率
PNPLA3基因
单核苷酸多态性
Fatty liver
Genes
Gene frequency
Patatin-like phospholipase domain-containingprotein 3PNPLA3
Singlenucleotidepolymorphism
