Limits...
Multiple Genetic Modifiers of Bilirubin Metabolism Involvement in Significant Neonatal Hyperbilirubinemia in Patients of Chinese Descent.

Yang H, Wang Q, Zheng L, Lin M, Zheng XB, Lin F, Yang LY - PLoS ONE (2015)

Bottom Line: Breastfeeding and the presence of the minor A allele of rs4148323 (UGTA*6) were correlated with an increased risk of hyperbilirubinemia (OR=2.17, P=0.02 for breastfeeding; OR=9.776, P=0.000 for UGTA*6 homozygote; OR=3.151, P=0.000 for UGTA*6 heterozygote); whereas, increasing gestational age and the presence of -TA7 repeat variant of UGT1A1 decreased the risk (OR=0.721, P=0.003 for gestational age; OR=0.313, P=0.002 for heterozygote TA6/TA7).This may support the use of genetic tests for clinical risk assessment.Furthermore, the established HRM assay can serve as an effective method for large-scale investigation.

View Article: PubMed Central - PubMed

Affiliation: Laboratory Medical Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, P. R. China; Central Laboratory, Chaozhou Central Hospital Affiliated to Southern Medical University, Chaozhou, Guangdong Province, P. R. China.

ABSTRACT
The potential for genetic variation to modulate neonatal hyperbilirubinemia risk is increasingly being recognized. A case-control study was designed to assess comprehensive contributions of the multiple genetic modifiers of bilirubin metabolism on significant neonatal hyperbilirubinemia in Chinese descendents. Eleven common mutations and polymorphisms across five bilirubin metabolism genes, namely those encoding UGT1A1, HMOX1, BLVRA, SLCO1B1 and SLCO1B3, were determined using the high resolution melt (HRM) assay or PCR-capillary electrophoresis analysis. A total of 129 hyperbilirubinemic infants and 108 control subjects were evaluated. Breastfeeding and the presence of the minor A allele of rs4148323 (UGTA*6) were correlated with an increased risk of hyperbilirubinemia (OR=2.17, P=0.02 for breastfeeding; OR=9.776, P=0.000 for UGTA*6 homozygote; OR=3.151, P=0.000 for UGTA*6 heterozygote); whereas, increasing gestational age and the presence of -TA7 repeat variant of UGT1A1 decreased the risk (OR=0.721, P=0.003 for gestational age; OR=0.313, P=0.002 for heterozygote TA6/TA7). In addition, the SLCO1B1 and SLCO1B3 polymorphisms also contributed to an increased risk of hyperbilirubinemia. This detailed analysis revealed the impact of multiple genetic modifiers on neonatal hyperbilirubinemia. This may support the use of genetic tests for clinical risk assessment. Furthermore, the established HRM assay can serve as an effective method for large-scale investigation.

No MeSH data available.


Related in: MedlinePlus

HRM analysis of 9 single base polymorphisms across the UGT1A1, SLCO1B1, SLCO1B3 and BLVRA genes.(a): rs4148323 G>A; (b): rs6742078 T>G; (c):rs35390940 C>A; (d): rs108124 A>G; (e): rs2306283 G>A; (f): rs4149056 T>C; (g): rs2117032 T>C; (h): rs2417940 T>C; (i): rs699512 A>G.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4493094&req=5

pone.0132034.g001: HRM analysis of 9 single base polymorphisms across the UGT1A1, SLCO1B1, SLCO1B3 and BLVRA genes.(a): rs4148323 G>A; (b): rs6742078 T>G; (c):rs35390940 C>A; (d): rs108124 A>G; (e): rs2306283 G>A; (f): rs4149056 T>C; (g): rs2117032 T>C; (h): rs2417940 T>C; (i): rs699512 A>G.

Mentions: HRM analysis was applied for the rapid genotyping of the 9 selected common single base variants in our study cohort. As shown in Fig 1, a heterozygous mutation could be easily distinguished from wild-type samples based on differences in the HRM curve shape. The HRM curve shapes for the homozygous mutations were similar to those of the wild-type subjects, and the homozygous mutations were detected by a modified HRM analytical strategy as described in our previous study [13]. Each SNP for the 50 samples was selected for direct sequencing. All the test samples were accurately genotyped as confirmed by the sequencing results. Therefore, we believed that HRM could be used as a general and rapid method for large-scale clinical investigation.


Multiple Genetic Modifiers of Bilirubin Metabolism Involvement in Significant Neonatal Hyperbilirubinemia in Patients of Chinese Descent.

Yang H, Wang Q, Zheng L, Lin M, Zheng XB, Lin F, Yang LY - PLoS ONE (2015)

HRM analysis of 9 single base polymorphisms across the UGT1A1, SLCO1B1, SLCO1B3 and BLVRA genes.(a): rs4148323 G>A; (b): rs6742078 T>G; (c):rs35390940 C>A; (d): rs108124 A>G; (e): rs2306283 G>A; (f): rs4149056 T>C; (g): rs2117032 T>C; (h): rs2417940 T>C; (i): rs699512 A>G.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493094&req=5

pone.0132034.g001: HRM analysis of 9 single base polymorphisms across the UGT1A1, SLCO1B1, SLCO1B3 and BLVRA genes.(a): rs4148323 G>A; (b): rs6742078 T>G; (c):rs35390940 C>A; (d): rs108124 A>G; (e): rs2306283 G>A; (f): rs4149056 T>C; (g): rs2117032 T>C; (h): rs2417940 T>C; (i): rs699512 A>G.
Mentions: HRM analysis was applied for the rapid genotyping of the 9 selected common single base variants in our study cohort. As shown in Fig 1, a heterozygous mutation could be easily distinguished from wild-type samples based on differences in the HRM curve shape. The HRM curve shapes for the homozygous mutations were similar to those of the wild-type subjects, and the homozygous mutations were detected by a modified HRM analytical strategy as described in our previous study [13]. Each SNP for the 50 samples was selected for direct sequencing. All the test samples were accurately genotyped as confirmed by the sequencing results. Therefore, we believed that HRM could be used as a general and rapid method for large-scale clinical investigation.

Bottom Line: Breastfeeding and the presence of the minor A allele of rs4148323 (UGTA*6) were correlated with an increased risk of hyperbilirubinemia (OR=2.17, P=0.02 for breastfeeding; OR=9.776, P=0.000 for UGTA*6 homozygote; OR=3.151, P=0.000 for UGTA*6 heterozygote); whereas, increasing gestational age and the presence of -TA7 repeat variant of UGT1A1 decreased the risk (OR=0.721, P=0.003 for gestational age; OR=0.313, P=0.002 for heterozygote TA6/TA7).This may support the use of genetic tests for clinical risk assessment.Furthermore, the established HRM assay can serve as an effective method for large-scale investigation.

View Article: PubMed Central - PubMed

Affiliation: Laboratory Medical Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, P. R. China; Central Laboratory, Chaozhou Central Hospital Affiliated to Southern Medical University, Chaozhou, Guangdong Province, P. R. China.

ABSTRACT
The potential for genetic variation to modulate neonatal hyperbilirubinemia risk is increasingly being recognized. A case-control study was designed to assess comprehensive contributions of the multiple genetic modifiers of bilirubin metabolism on significant neonatal hyperbilirubinemia in Chinese descendents. Eleven common mutations and polymorphisms across five bilirubin metabolism genes, namely those encoding UGT1A1, HMOX1, BLVRA, SLCO1B1 and SLCO1B3, were determined using the high resolution melt (HRM) assay or PCR-capillary electrophoresis analysis. A total of 129 hyperbilirubinemic infants and 108 control subjects were evaluated. Breastfeeding and the presence of the minor A allele of rs4148323 (UGTA*6) were correlated with an increased risk of hyperbilirubinemia (OR=2.17, P=0.02 for breastfeeding; OR=9.776, P=0.000 for UGTA*6 homozygote; OR=3.151, P=0.000 for UGTA*6 heterozygote); whereas, increasing gestational age and the presence of -TA7 repeat variant of UGT1A1 decreased the risk (OR=0.721, P=0.003 for gestational age; OR=0.313, P=0.002 for heterozygote TA6/TA7). In addition, the SLCO1B1 and SLCO1B3 polymorphisms also contributed to an increased risk of hyperbilirubinemia. This detailed analysis revealed the impact of multiple genetic modifiers on neonatal hyperbilirubinemia. This may support the use of genetic tests for clinical risk assessment. Furthermore, the established HRM assay can serve as an effective method for large-scale investigation.

No MeSH data available.


Related in: MedlinePlus