胆绿素还原酶A基因多态性与福建地区新生儿高胆红素血症的相关性  

Association of biliverdin reductase A gene polymorphisms with neonatal hyperbilirubinemia from Fujian area

作　　者：周进福[1] 杨长仪[2] 陈庶伟[2] 曾颖琳[1] 王旌[1] 赵红[1] 陈瑶[1] 林枫[1] 林丹[3] 朱文斌[1] 

机构地区：[1]福建省妇幼保健院,福建医科大学附属医院新生儿疾病筛查中心,福州350001 [2]福建省妇幼保健院,福建医科大学附属医院新生儿科,福州350001 [3]福建省妇幼保健院,福建医科大学附属医院妇产科,福州350001

出　　处：《中华实用儿科临床杂志》2018年第2期108-112,共5页Chinese Journal of Applied Clinical Pediatrics

基　　金：福建省卫生计生委青年科研课题（2015-1-17）;福建省妇幼保健院院内科研课题（妇保院研15-21）

摘　　要：目的探讨胆绿素还原酶A（biliverdin reductase A，BLVRA）基因单核苷酸多态性（single nucleotide polymorphisms，SNPs）与福建地区新生儿高胆红素血症的相关性。方法应用时间飞行质谱技术对286例高胆红素血症新生儿（病例组）和250例健康对照组BLVRA基因的5个SNP位点（rs699512、rs1802846、rs7738、rs1637530和rs2302032）进行基因分型。分析比较基因型、等位基因及单体型频率在2组间的分布差异。结果所选BLVRA基因5个SNPs位点均符合Hardy-Weinberg平衡检验（均P〉0.05）。病例组rs699512和rs1637530位点等位基因和基因型频率与健康对照组比较，差异均有统计学意义（均P〈0.05）；其余3个多态性位点的基因型及等位基因频率与健康对照组比较，差异均无统计学意义（均P〉0.05）。在隐性模式下，病例组rs699512 GG基因型（OR＝0.494，95%CI：0.276～0.886，P＝0.018）频率明显低于健康对照组；在显性模式下，病例组rs699512 GG＋AG基因型频率（OR＝0.678，95%CI：0.482～0.954，P＝0.026）和rs1637530 TT＋CT（OR＝0.627，95%CI：0.444～0.885，P＝0.008）明显低于健康对照组，差异均有统计学意义。联合所有位点进行单体型分析发现，rs1637530、rs2302032、rs699512和rs1802846位点在同一连锁不平衡区域，以单体型CGAT为对照进行分析，单体型TGGT、CTAT和CGGT在2组间差异均有统计学意义（均P〈0.05），且可降低患高胆红素血症的风险（OR＝0.588、0.687、0.501，95%CI：0.434～0.797、0.496～0.952、0.250～1.004）。结论BLVRA基因rs699512和rs1637530位点多态性与福建地区新生儿高胆红素血症密切相关，rs699512位点A等位基因和rs699512位点C等位基因可能是新生儿高胆红血症的易感基因。ObjectiveTo assess the association of single nucleotide polymorphisms（SNPs）of biliverdin reductase A （BLVRA） with neonatal hyperbilirubinemia from Fujian area.MethodsA total of 286 patients with neonatal hyperbilirubinemia and 250 healthy controls were enrolled.Genotypes of 5 SNPs within BLVRA gene including rs699512, rs1802846, rs7738, rs1637530 and rs2302032 were determined with matrix-assisted laser desorption ionization/time of flight mass spectrometer.The frequencies of genotype, allele, haplotype and their differentiations were analyzed.ResultsAll 5 SNPs had conformed to Hardy-Weinberg equilibrium （all P〉0.05）. rs699512 and rs1637530 showed a significant difference between the 2 groups in both allelic and genotypic frequencies（all P〈0.05）, but no significant differences were found in the other SNPs（all P〉0.05）. In recessive model, the frequency of rs699512 GG genotype of patients was significantly lower than that of the healthy control group（OR=0.494, 95%CI： 0.276-0.886, P=0.018）, while in dominant model, the frequencies of rs699512 GG＋ AG and rs1637530 TT＋ CT genotype of patients were significantly lower than that of the healthy control group（OR=0.678, 0.627; 95%CI： 0.482-0.954, 0.444-0.885; P=0.026, 0.008）. Based on linkage disequilibrium analysis and haplotype construction, rs1637530, rs2302032, rs699512 and rs1802846 locus in the same area.Based on haplotype CGAT, TGGT, CTAT and CGGT had significant differences between the 2 groups（all P〈0.05）, and could reduce the risk of high blood bilirubin（OR=0.588, 0.687, 0.501; 95%CI： 0.434-0.797, 0.496-0.952, 0.250-1.004）.Conclusionsrs699512 and rs1637530 may be associated with neonatal hyperbilirubinemia, A allele in rs699512 and C allele in rs1637530 may be associated with significantly increased risk of neonatal hyperbilirubinemia.

关 键 词：高胆红素血症 婴儿 新生 胆绿素还原酶A基因 单核苷酸多态性 

分 类 号：R722.1[医药卫生—儿科]