目的 探讨尿苷二磷酸葡萄糖醛基转移酶1A1（UGT1A1）、有机阴离子转运体1B1（SLCO1B1）及葡萄糖-6-磷酸脱氢酶（G6PD）基因多态性与中国西南地区新生儿高胆红素血症的易感关联性。方法 选取2016年9月至2019年12月籍贯为云南省、贵州省、四川省的新生儿高胆红素血症患儿190例为病例组,同时随机选取200例同期住院的无黄疸新生儿为对照组。提取外周血DNA,采用Sequenom芯片进行17个SNP位点分型检测。比较两组间基因型与等位基因频率分布差异。结果 病例组190例,男98例、女92例,平均胎龄（38.7±1.2）周。对照组200例,男116例、女84例,平均胎龄（38.9±1.3）周。病例组UGT1A1基因rs873478、rs34946978和rs4148323位点等位基因频率均高于对照组,病例组SLCO1B1基因rs72559748位点等位基因频率低于对照组,差异有统计学意义（P<0.05）。2例男性高胆红素血症患儿检出G6PD基因rs72554664变异,检出率为1.05%。病例组和对照组之间风险等位基因个数分布差异有统计学意义（P<0.05）,病例组风险等位基因≥2个的比例较高。结论 UGT1A1基因rs873478、rs34946978和rs4148323多态性与中国西南地区新生儿高胆红素血症发生风险增加有关。SLCO1B1基因多态性与该地区新生儿高胆红素血症发生无显著关联。G6PD酶活性缺乏可能不是该地区新生儿高胆红素血症的主要风险因素。

Objective To investigate the relationship between uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1), organic anion transporter family member 1B1 (SLCO1B1) and glucose-6-phosphate dehydrogenase (G6PD) gene polymorphisms and neonatal hyperbilirubinemia in southwest China. Methods A total of 190 neonates with neonatal hyperbilirubinemia from September 2016 to December 2019 in Yunnan, Guizhou and Sichuan provinces were selected as the study group, and 200 neonates without jaundice who were hospitalized during the same period were randomly selected as the control group. Genomic DNA was extracted from venous blood and 17 SNPs sites were genotyped by Sequenom-specific SNP detection. Genotype and allele frequency were compared between the study and control groups. Results There were 190 patients (98 boys and 92 girls) in the study group, and the average gestational age was (38.7±1.2) weeks. In the control group, there were 200 neonates (116 boys and 84 girls), and the average gestational age was (38.9±1.3) weeks. The allele frequencies of UGT1A1 rs873478, rs34946978 and rs4148323 were higher in the study group than those in the control group, while the allele frequency of SLCO1B1 rs72559748 was lower in the study group than that in the control group, and the differences were statistically significant (P<0.05). The G6PD rs72554664 variant was detected in two boys with hyperbilirubinemia, and the detection rate was 1.05%. There was significant difference in the distribution of risk alleles between the study group and the control group (P<0.05), and the proportion of risk alleles ≥2 was higher in the study group. Conclusions The UGT1A1 rs873478, rs34946978 and rs4148323 polymorphisms were associated with higher risk of neonatal hyperbilirubinemia in southwest China. The SLCO1B1 polymorphism was not significantly associated with the incidence of neonatal hyperbilirubinemia and lack of G6PD enzyme activity may not be a major risk factor for neonatal hyperbilirubinemia in this region.