Journal of Isfahan Medical School

Journal of Isfahan Medical School

Analysis of Genetic Variation of rs4148326 Marker Located in UGT1A1 Gene Region: An Informative Marker for Molecular Diagnosis of Crigler-Najjar Syndrome

Document Type : Original Article (s)

Authors
Zakiyeh Nadeali 1
Amin Karimi 1
Sadeq Vallian-Borujeni 2
1 Department of Biology, School of Sciences, University of Isfahan, Isfahan, Iran
2 Professor, Department of Biology, School of Sciences, University of Isfahan, Isfahan, Iran
Abstract
Background: Crigler-Najjar syndrome is a rare, autosomal recessive disorder characterized by unconjugated, non-hemolytic hyperbilirubinemia. The disease is caused by mutations in the UGT1A1 gene, which result in the decrease or lack of the UGT1A1 enzyme activity and thus, lack of bilirubin conjugation with glucuronic acid. Molecular diagnosis of the syndrome has been essentially based on direct mutation analysis. However, due to a large number of mutations associated with the disease, direct mutation analysis is expensive and time consuming. Alternatively, indirect analysis of mutations using linkage analysis by means of polymorphic markers is proposed. Several polymorphic markers associated with the UGT1A1 gene have been studied.Methods: Using bioinformatic analysis of these markers, the single nucleotide polymorphism (SNP) rs4148326 with the C/T sequence, located at 5' region of the gene was selected. Analysis of the marker was performed by genotyping of 186 unrelated healthy individuals in the Isfahanian population, Iran, using tetra-primer amplification refractory mutation system polymerase chain reaction (Tetra-Primer ARMS PCR) technique. Statistical analysis of the results was performed using the GENEPOP software.Findings: The heterozygosity of rs4148326 the marker was 62.9% and the allele frequency for T and C allele was 66.94% and 33.06%, respectively. Analysis of deviations from Hardy-Weinberg equilibrium demonstrated that the Isfahanian population was in equilibrium (P < 0.001) for rs4148326 locus.Conclusion: The data suggested that rs4148326 could be introduced as an informative marker for molecular diagnosis of Crigler-Najjar syndrome in a representative sample of the Iranian population.
Keywords
Single Nucleotide Polymorphism
UGT1A1 gene
Crigler-Najjar syndrome
Tetra-primer amplification refractory mutation system polymerase chain reaction
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Journal of Isfahan Medical School
Volume 31, Issue 260 - Serial Number 260
September and October 2014
Pages 1821-1828

  • Receive Date 18 August 2013
  • Accept Date 06 April 2022