中国人内源性高甘油三酯血症患者ATP结合盒转运子A1基因R219K多态性研究

Analysis of ATP binding cassette A1 gene R219K polymorphism in patients with endogenous hypertriglyceridemia in Chinese population

目的研究ATP结合盒转运子A1（ATP binding cassette Al，ABCA1）基因R219K多态性是否与中国人内源性高甘油三酯血症（hypertriglyceridemia，HTG）有关联，为探讨本病的分子遗传基础提供依据。方法应用聚合酶链反应一限制性片段长度多态性分析法，对成都地区309名汉族人（200名正常人和109例内源性高甘油三酯血症患者）ABCA1基因R219K多态性位点进行分析。结果中国人ABCA1基因R219K多态位点K等位基因频率在对照组和H他组分别为0．472与0．436；HTG组和对照组R219K位点之间基因型和等位基因的频率差异无统计学意义。对照组和HTG组KK基因型携带者血清高密度脂蛋白胆固醇（high density lipoprotein-cholesterol，HDL-C）水平均较相应组RR基因型携带者显著升高[（1．48±0．45）mmol／L vs（1．27±0．29）mmol／L，P〈0．05；（1．07±0．30）mmol／Lvs（0．87±0．19）mmol／L，P〈0．05]；对照组RK型携带者血清甘油三酯水平较RR型携带者显著降低[（1．22±0．37）mmol／L vs（1．41±0．84）mmol／L，P〈0．05]，HTG组血清甘油三酯在RR、RK、KK型之间有逐渐降低的趋势[（3．82±2．02）mmol／L vs（3．42±1．67）mmol／L vs（3．33±1．43）mmol／L，P〉0．05]；HTG组K等位基因携带者（RK或KK型者）总胆固醇（total cholesterol，TC）／HDL-C比值均较RR型携带者显著降低（KK vs RK vs RR：4．82±1．28vs5．42±1．62vs6．33±1．70，P〈0．05）。结论ABCA1基因R219K多态性不仅与中国成都地区正常汉族人血清HDL-C、甘油三酯含量有关，而且还与内源性高甘油三酯血症患者血清HDL-C水平、TC／HDL-C比值相关联。

Objective To investigate the variations of ATP binding cassette A1 （ABCA1） gene and its relation to endogenous hypertriglyceridemia （HTG） in Chinese population. Methods A total of three hundred and nine subjects （one hundred and nine endogenous hypertriglyceridemics and 200 healthy controls） from a population of Chinese Hart nationality in Chengdu area were studied using restriction fragment length polymorphism （RFLP） amplified by polymerase chain reaction （PCR）. Results The frequency of K allele at R219K site 0.472 and 0.436 in normal and HTG group, respectively. No significant difference between normal control and HTG group was found in both allele and genotype fre- quencies. In both normal and HTG groups, subjects with genotype KK had a higher serum mean concentration of high density lipoprotein-cholesterol （HDL-C） when compared with those with genotype RR, respectively （1.48 ± 0.45 mmol/ L vs 1.27 ± 0.29 mmol/L, P 〈 0.05; 1.07 ± 0.30 mmol/L vs 0.87 ± 0.19 mmol/L, P 〈 0.05）. In normal group, subjects with genotype RK had a lower triglyceride （TG） level compared with those with genotype RR （ 1.22 ± 0.37 mmol/L vs 1.41 ± 0.84 mmol/L, P 〈 0.05）. In addition, the subjects carrying K allele in HTG group had a decreased total cholesterol （TC）/HDL- C ratio compared with those with genotype RR（KK vs RK vs RR： 4.82 ± 1.28 vs 5.42 ± 1. 62 vs 6.33 ± 1.70, P 〈 0.05）. Conclusion These results suggest that R219K polymorphism in ABCA1 gene is not only associated with serum HDL-C and TG levels in healthy Chinese subjects in Chengdu area, but also with HDL-C level and TC/I-IDL-C ratio in subjects with endogenous HTG.