高尿酸血症患者血清ABCG2基因rs2231142位点单核苷酸多态性观察

Single nucleotide polymorphism of serum ABCG2 gene rs2231142 in patients with hyperuricemia

目的观察高尿酸血症患者血清三磷酸腺苷结合转运蛋白G超家族成员2(ABCG2)基因rs2231142位点单核苷酸多态性(SNPs)。方法高尿酸血症患者357例为高尿酸血症组,正常对照人群932例为正常组,抽取两组静脉血提取DNA,PCR法扩增目的基因,采用i MLDR方法分析ABCG2基因rs2231142位点基因型。检测两组血清SUA、尿素氮(BUN)、肌酐(CREA)等肾功能相关指标,检测两组尿尿酸(UA),测算两组肾小球滤过率s GFR。结果高尿酸血症组ABCG2基因rs2231142位点基因型GG、GT+TT分布频率分别为42. 9%(153/357)、57. 1%(204/357),对照组分别为53. 6%(500/932)、46. 4%(432/932),二者比较,P <0. 05;等位基因G、T的分布频率分别为65. 3%(466/714)、34. 7%(248/714);对照组分别为75. 7%(1 346/1 864)、24. 3%(518/1 864),二者比较,P<0. 05。随尿酸水平升高,GT+TT基因型分布频率逐渐升高,GG基因型分布频率逐渐降低,T等位基因分布逐渐升高,G等位基因分布逐渐降低(P均<0. 05)。ABCG2基因rs2231142位点GT+TT基因型携带者罹患高尿酸血症的风险性是ABCG2基因rs2231142位点GG基因型携带者的1. 23倍(95%CI为1. 101～1. 381,P <0. 05),T等位基因携带者罹患高尿酸血症的风险性是G基因型携带者的1. 43倍(95%CI为1. 256～1. 628,P <0. 05)。s GFR、SUA与ABCG2基因rs2231142位点之间的交互作用差异有统计学意义(95%CI分别为1. 34～37. 39,1. 51～17. 86; OR分别为7. 43,5. 36; P均<0. 05)。与ABCG2基因rs2231142位点GG基因型比较,GT基因型高尿酸血症患者血清SUA、BUN和CREA水平升高,s GFR降低(P均<0. 05);与GT基因型比较,TT基因型高尿酸血症患者血清SUA、BUN和CREA水平升高,s GFR降低(P均<0. 05)。结论高尿酸血症患者ABCG2基因rs2231142位点GT+TT基因型分布频率高,T等位基因突变频率较高。ABCG2基因rs2231142位点GT+TT基因型、T等位基因携带者患高尿酸血症的风险性较高。ABCG2基因rs2231142位点突变的高尿酸血症患者可能出现肾功能损害。

ObjectiveTo observe the single nucleotide polymorphisms(SNPs)of the ATP-binding cassette transporer G2(ABCG2)gene rs2231142 site in hyperuricemia patients.MethodsA total of 357 patients with hyperuricemia(hyperuricemia group)and 932 healthy controls(normal control group)were selected.We extracted DNA from the venous blood of the two groups,and the target gene was amplified by PCR,and the genotype in the rs2231142 locus of ABCG2 gene was analyzed by iMLDR method.The renal function indexes of serum SUA,urea nitrogen(BUN),and creatinine(CREA)were detected in the two groups.Uric acid(UA)was detected and the glomerular filtration rate sGFR was calculated.ResultsThe distribution frequencies of GG and GT+TT at rs2231142 of ABCG2 gene were 42.9%(153/357)and 57.1%(204/357)in the hyperuricemia group,versus 53.6%(500/932)and 46.4%(432/932)in the control group,both P<0.05.The distribution frequencies of alleles G and T were 65.3%(466/714)and 34.7%(248/714),which were 75.7%(1346/1864)and 24.3%(518/1864)in the control group,respectively,both P<0.05.With the increase of uric acid level,the distribution frequency of genotype GT+TT gradually increased,the distribution frequency of GG genotype gradually decreased,the distribution of T allele gradually increased,and the distribution of G allele gradually decreased(all P<0.05).The risk of hyperuricemia was 1.23 times higher in the GT+TT carriers of ABCG2 rs2231142 than in the GG carriers of ABCG2 rs2231142(95%CI:1.101-1.381,0x09 P<0.05),carriers with T allele were 1.43 times more likely to develop hyperuricemia than carriers with G genotype(95%CI:1.256-1.628,P<0.05).The difference of interaction between sGFR,SUA and ABCG2 gene rs2231142 was statistically significant(95%CI:1.34-37.39,1.51-17.86;OR=7.34 and 5.36;P<0.05).Compared with patients with GG genotype at rs2231142 of ABCG2 gene,the serum levels of SUA,BUN,and CREA increased and sGFR decreased in the hyperuricemia patients with GT genotype(all P<0.05).The hyperuricemia patients with TT genotype had increased serum SUA,BUN and CREA levels and decreased sGFR compared with patients with GT genotype(all P<0.05).ConclusionsThe GT+TT genotype distribution frequency and T allele mutation frequency of ABCG2 gene rs2231142 in hyperuricemia patients are high.Carriers with GT+TT genotype and T allele of ABCG2 gene rs2231142 have a higher risk of hyperuricemia.Renal impairment may occur in hyperuricemia patients with ABCG2 gene rs2231142 mutation.