Effects of Gly71Arg mutation in UGT1A1 gene on neonatal hyperbilirubinemia: a systematic review and meta-analysis

J Matern Fetal Neonatal Med. 2019 May;32(10):1575-1585. doi: 10.1080/14767058.2017.1410789. Epub 2017 Dec 10.

Abstract

Objective: The associations between Gly71Arg polymorphism in the coding region of uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) gene and the risk of neonatal hyperbilirubinemia remained controversial. Therefore, a meta-analysis of observational studies has been conducted to assess the relationship between UGT1A1 gene polymorphism of Gly71Arg and neonatal hyperbilirubinemia susceptibility.

Methods: An electronic literature search from online databases, such as PubMed, Embase, Cochrane, and Scopus was conducted to identify eligible studies. The effect summary odds ratio (OR) with 95% confidence interval (CI) was used to estimate the strength of association in the fixed or random effects model, based on the absence or presence of heterogeneity.

Results: A total of 32 eligible studies involving 2634 cases of neonatal hyperbilirubinemia and 4996 controls were enrolled in this meta-analysis. The combined results showed that UGT1A1 Gly71Arg polymorphism was associated with an increased risk of neonatal hyperbilirubinemia in all genetic models (homozygote model: OR = 6.12, 95% CI = 4.42-8.46; heterozygote model: OR = 2.06, 95% CI = 1.82-2.33; dominant model: OR = 2.44, 95% CI = 2.03-2.93; recessive model: OR = 4.79, 95% CI = 3.48-6.59, and allelic model: OR = 2.37, 95% CI = 1.98-2.82). Subgroup analysis by ethnicity strongly validated this correlation in Asians but slightly in Caucasian population.

Conclusions: This meta-analysis confirms that UGT1A1 Gly71Arg polymorphism significantly increases the risk of neonatal hyperbilirubinemia in Asian population, but results from the Caucasians were conflicting and further well-designed epidemiological studies are, therefore, required to more adequately assess this correlation.

Keywords: Meta-analysis; UGT1A1; neonatal hyperbilirubinemia; polymorphism.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Asian People
  • Case-Control Studies
  • Female
  • Genetic Predisposition to Disease*
  • Glucuronosyltransferase / genetics*
  • Humans
  • Hyperbilirubinemia, Neonatal / genetics*
  • Infant, Newborn
  • Mutation / genetics*
  • Observational Studies as Topic
  • Polymorphism, Genetic
  • Polymorphism, Single Nucleotide
  • Pregnancy
  • Risk Factors
  • White People

Substances

  • UGT1A1 enzyme
  • Glucuronosyltransferase