Analysis Of Ugt1A1Gene Mutations In Guangxi Heiyi Zhuang And Han Neonates With Unconjugated Hyperbilirubinemia

Objective:To study the characteristics of uridine diphosphate-glucuronosyl transferase1A1(UGT1A1) gene mutations in Guangxi Heiyi Zhuang and Han neonateswith unconjugated hyperbilirubinemia, to explore the differences of mutationsbetween the two ethnic groups and its impact on the occurrence anddevelopment of neonatal unconjugated hyperbilirubinemia.Methods:1. Molecular biology methods such as polymerase chain reaction (PCR),gene sequencing were used to detect the mutations in promoter TATA-box andfive exons of UGT1A1gene in all subjects (case group:100cases of HeiyiZhuang and Han respectively；control group:100cases of Heiyi Zhuang,80cases of Han).2. To analysis the difference in genotype distribution and allele frequenciesof UGT1A1gene mutations between different groups, and disscuss their impacton neonatal unconjugated hyperbilirubinemia and bilirubin levels. Results:1. Nine types of UGT1A1gene mutations were detected in this study: the(TA)7insertion mutation in promoter TATA-box;189C＞T,211G＞A and686C＞A in exon1;1352C＞T,1459C＞T,1491C＞T,1941C＞G and2042C＞G inexon5. Their mutation rate in the case group were19.5%,1.0%,34.5%,0.5%,0.5%,0.5%,1.0%,11.5%and11.5%respectively.The1459C＞T mutation wasfirst found in China.2. There were significant differences in the genotype distribution of UGT-1A1211G＞A mutation whether it was compared between the case and controlgroups or between the two ethnic groups (P＜0.05). The A allele frequency washigher in the case group than in the control group, and higher in Han than inHeiyi Zhuang within the case group or control group (P＜0.01). While statisticaldifference in the genotype distribution and allele frequencies of (TA)7insertionand1941C＞G/2042C＞G mutations was not found between those groups (P＞0.05).3. The odd ratio(OR) and95%confidence interval(CI) of211G＞A,(TA)7and1941C＞G/2042C＞G mutations associated with the occurence of neonatalunconjugated hyperbilirubinemia in Heiyi Zhuang were3.932(1.745,8.858),0.846(0.440,1.629) and0.899(0.364,2.222) respectively, while in Han were2.231(1.163,4.278),0.058(0.249,1.034) and1.046(0.433,2.528) respectively.4. Among the patients at the age of day3, the TSB and UCB in those whocarried single homozygous211G＞A mutation were significantly higher thanthose who didn’t carry any mutation (P＞0.05), while there were no statisticaldifference between those who carried single or compound heterozygous211G＞A,(TA)6/7, heterozygous1941C＞G/2042C＞G mutations and those whodidn’t carry any mutation (P＞0.05). Conclusions:1.211G＞A mutation in exon1may be the mutational hotspot of UGT1A1gene in Guangxi Heiyi Zhuang and Han neonates with unconjugatedhyperbilirubinemia.2. There may be ethnic difference in UGT1A1211G＞A mutation betweenGuangxi Heiyi Zhuang and Han populations, it seems more common in Hanthan Heiyi Zhuang, while there may be no ethnic difference in (TA)7insertionand1941C＞G/2042C＞G mutations between the two ethnic groups.3. UGT1A1211G＞A mutation is a risk factor for neonatal unconjugatedhyperbilirubinemia in Guangxi Han as well as Heiyi Zhuang. But the (TA)7insertion and1941C＞G/2042C＞G mutations may not be associated with it.4. The bilirubin level may be correlated with the homozygous or heterozy-gous status of UGT1A1gene mutations. Homozygous211G＞A mutation is animportant hereditary factor for neonatal unconjugated hyperbilirubinemia inGuangxi.