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

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
• neonatal hyperbilirubinemia
• polymorphism
• UGT1A1

Acknowledgments

The authors would like to thank Dr Saeed Eslami at the Department of Medical Bioinformatics of Mashhad University of Medical Sciences, for assisting in the statistical analysis.

Disclosure statement

The authors declare that there are no conflicts of interest.

Additional information

Funding

This work was supported by Mashhad University of Medical Sciences [grant number 960848].