PPM1K基因rs1440581、rs7678928位点单核苷酸多态性对血清支链氨基酸水平的影响及其与心血管疾病的关系

Effect of PPM1K gene single nucleotide polymorphisms rs1440581 and rs7678928 on serum branched chain amino acid levels and subsequent cardiovascular disease risk

目的明确PPM1K基因rs1440581、rs7678928位点单核苷酸多态性是否影响中国人群血清支链氨基酸水平,并探讨其与心血管疾病风险因素之间的关系。方法采用随机抽样的方法从2014年8月至9月在江苏省淮安市第二人民医院体检者中抽取234名受试者,采用二代测序检测其PPM1K基因rs1440581、rs7678928位点的基因型,并进行健康指导干预及4年随访调查。利用SPSS 22.0软件分析2位点单核苷酸多态性与血清支链氨基酸水平及随访4年前后其他心血管疾病风险因素之间的关系。结果PPM1K基因rs1440581、rs7678928位点各基因型频率分布均符合Hardy-Weinberg平衡(P>0.05)。rs1440581位点各基因型比较,发现携带CC基因型者基线血清缬氨酸(P=0.022)及总支链氨基酸(P=0.026)水平较TT者高;rs7678928位点各基因型血清支链氨基酸水平未发现差异有统计学意义(P>0.05)。随访后rs1440581位点各基因型的血压及血清三酰甘油、高密度脂蛋白胆固醇、谷草转氨酶存在统计学差异(P<0.05);rs7678928位点各基因型血压及血清高密度脂蛋白胆固醇存在统计学差异(P<0.05)。在同等干预措施下rs1440581位点CC基因型携带者、rs7678928位点TT基因型血清空腹血糖、三酰甘油、高密度脂蛋白胆固醇、谷丙转氨酶、谷草转氨酶、血肌酐等心血管疾病危险因素改善获益较小。结论PPM1K基因rs1440581位点C等位基因与血清缬氨酸、总支链氨基酸水平升高以及心血管疾病风险因素相关;rs1440581位点CC基因型可能是替代基线血清支链氨基酸浓度作为4年后心血管疾病风险因素变化更好的标志物。

Objective To investigate the effect of PPM1K gene single nucleotide polymorphisms rs1440581 and rs7678928 on serum branched chain amino acid levels and subsequent cardiovascular disease(CVD)risk within 4 years.Methods A total of 234 subjects randomly selected from Huai'an Second People's Hospital from August to September 2014 were detected for the genotypes of rs1440581 and rs7678928 of PPM1K gene by second-generation sequencing.All subjects were given health guidance and followed for four years.The associations between the two polymorphisms and the levels of serum branched chain amino acids and other risk factors of cardiovascular disease were analyzed with SPSS 22.0 software.Results The distribution frequencies of genotypes of rs1440581 and rs7678928 were consistent with the Hardy-Weinberg equilibrium(P>0.05).The baseline levels of serum valine(P=0.022)and total branched chain amino acids(P=0.026)in subjects with CC genotype of rs1440581 were higher than those with TT genotype.There were no significant differences in the levels of serum branched chain amino acids among genotypes of rs7678928.After four-year follow-up,there were statistical differences in the levels of blood pressure,serum triglyceride,high-density lipoprotein cholesterol and aspartate aminotransferase among each genotype of rs1440581(P<0.05).The levels of blood pressure and serum highdensity lipoprotein cholesterol in each genotype of rs7678928 were statistically different(P<0.05).Under the same intervention measures,there were little improvement in the levels of serum FPG,TG,HDL-C,ALT,AST,and CREA in subjects with rs1440581 CC genotype and rs7678928 TT genotype.Conclusion Allele C of rs1440581 of PPM1K gene is associated with elevated serum valine,total branched chain amino acids,and CVD risk.The CC genotype of rs1440581 may be a better marker for the risk of CVD as substitutes for the levels of baseline serum branched amino acids after 4 years.