Distribution of selected gene polymorphisms of UGT1A1 in a Saudi population

Alkharfy, Khalid M.; Alghamdi, Abdulaziz G.; Bagulb, Khawla M.; Al-Jenoobi, Fahad I.; Al-Mohizea, Abdullah M.; Al‐Muhsen, Saleh; Halwani, Rabih; Parvez, Mohammad K.; Al‐Dosari, Mohammed S.

doi:10.5114/aoms.2013.37012

Cited by 11 publications

(13 citation statements)

References 29 publications

(32 reference statements)

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“…In this study, we observed that the presence of at least one of the rare alleles of this polymorphism appears to increase the chances of developing CRC by 13-times. In the literature, some studies show that alleles *36 and *37 are absent or extremely rare in different populations[ 70 , 71 ], but there are no studies relating the association of these alleles with the development of CRC. Although little is known about *36 and *37 alleles, it is possible that the presence of such alleles could lead to a decreased activity of the UGT1A1 gene, inducing the carcinogenesis process.…”

Section: Discussionmentioning

confidence: 99%

Analysis of 12 variants in the development of gastric and colorectal cancers

Cavalcante

Amador

Santos

et al. 2017

WJG

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AIMTo evaluate the relation between 12 polymorphisms and the development of gastric cancer (GC) and colorectal cancer (CRC).METHODSIn this study, we included 125 individuals with GC diagnosis, 66 individuals with CRC diagnosis and 475 cancer-free individuals. All participants resided in the North region of Brazil and authorized the use of their samples. The 12 polymorphisms (in CASP8, CYP2E1, CYP19A1, IL1A, IL4, MDM2, NFKB1, PAR1, TP53, TYMS, UGT1A1 and XRCC1 genes) were genotyped in a single PCR for each individual, followed by fragment analysis. To avoid misinterpretation due to population substructure, we applied a previously developed set of 61 ancestry-informative markers that can also be genotyped by multiplex PCR. The statistical analyses were performed in Structure v.2.3.4, R environment and SPSS v.20.RESULTSAfter statistical analyses with the control of confounding factors, such as genetic ancestry, three markers (rs79071878 in IL4, rs3730485 in MDM2 and rs28362491 in NFKB1) were positively associated with the development of GC. One of these markers (rs28362491) and the marker in the UGT1A1 gene (rs8175347) were positively associated with the development of CRC. Therefore, we investigated whether the joint presence of the deleterious alleles of each marker could affect the development of cancer and we obtained positive results in all analyses. Carriers of the combination of alleles RP1 + DEL (rs79071878 and rs28361491, respectively) are at 10-times greater risk of developing GC than carriers of other combinations. Similarly, carriers of the combination of DEL + RARE (rs283628 and rs8175347) are at about 12-times greater risk of developing CRC than carriers of other combinations.CONCLUSIONThese findings are important for the comprehension of gastric and CRC development, particularly in highly admixed populations, such as the Brazilian population.

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Section: Discussionmentioning

confidence: 99%

Analysis of 12 variants in the development of gastric and colorectal cancers

Cavalcante

Amador

Santos

et al. 2017

WJG

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“…However, it is lower than the Chinese [25], Malay [25], Indian [25] and Japanese [8] populations. Additionally, the allele frequencies of the heterozygous (A/G) variant of UGT1A1*6 in the Iranian population is higher than that of the Chinese [25], Malay [25], Indian [25], Saudi Arabia [27] and African-American [28] populations, while it is lower than the Japanese population [8] (table 3; fig. 7).…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, the UGT1A1*6 genotypes, including G/G, A/G and A/A in different ethnicities, including Lure, Azari, Persian, Kurdish, Arab, Baluch and Caspian, is considered as an important determinant for the prevention of the harmful effects of drugs and drug interaction, ultimately leading to better survival and reduced mortality risk. The allele frequencies of the homozygous (A/A) variant of UGT1A1*6 are higher in the Iranian population than in Saudi Arabia [27] and African-American [28] populations. However, it is lower than the Chinese [25], Malay [25], Indian [25] and Japanese [8] populations.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of the UGT1A1*6 (c.211G>A) Polymorphism and Prediction of Irinotecan Toxicity in Iranian Populations of Different Ethnicities

et al. 2014

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Background: Pharmacogenetic studies on irinotecan treatment in patients with metastatic colorectal cancer have indicated that genetic polymorphisms in UGT1A1*6 can lead to decreased enzyme activity and accumulation of the toxic metabolite SN-38. Here, we compared the prevalence of UGT1A1*6 in an Iranian population of different ethnicities with those of other populations. Materials and Methods: A total of 300 healthy people of different ethnic groups including Persian, Azari, Lure, Kurdish, Arab, Baluch and Caspian in the Iranian population were enrolled. Genotyping of the UGT1A1*6 alleles (G/G, A/G, A/A) was performed by polymerase chain reaction-restriction fragment length polymorphism and direct genomic DNA sequencing. Result: The most predictive genotype among the Iranian ethnic groups, especially Persian, was the G/G genotype (wild-type genotype). The frequency of the A/G genotype among the Persian, Azari, Lure, Kurdish, Arab, Baluch and Caspian ethnicities were 15.69% (n = 27), 11.11% (n = 8), 5.88% (n = 1), 9.09% (n = 1), 10% (n = 1), 20% (n = 1) and 0% (n = 0), respectively. Only one person with Persian ethnicity was homozygous for the mutation in UGT1A1*6 (0.58%). Additionally, the frequency of the A and G alleles in Iranians was 6.83 and 93.16%, respectively. Conclusion: The identification of the UGT1A1*6 alleles is necessary among the different Iranian ethnic groups before irinotecan therapy, suggesting that genotyping would be helpful for clinicians to optimize chemotherapy or identify individuals at risk of adverse drug reactions before clinical trials.

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“…Gilbert syndrome, (TA)n promoter polymorphism of the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene, is the most commonly inherited decreased bilirubin glucuronidation disorder. 11 However, its background prevalence (3-16%) [12][13][14][15][16] is out of proportion with the prevalence of G6PD deficiency-associated hyperbilirubinemia (20-70%). 1,3,17,18 Paradoxically, the incidence of significant hyperbilirubinemia is significantly lower in Africans than Asians, despite Gilbert syndrome being more common in the former (36 vs 3%).…”

Section: Prevalence Of Gilbert Syndrome Is Out Of Proportion With Thementioning

confidence: 99%

Decreased Glutathione S-transferase Level and Neonatal Hyperbilirubinemia Associated with Glucose-6-phosphate Dehydrogenase Deficiency: A Perspective Review

Al-Abdi

2016

Amer J Perinatol

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Classically, genetically decreased bilirubin conjugation and/or hemolysis account for the mechanisms contributing to neonatal hyperbilirubinemia associated with glucose-6-phosphate dehydrogenase (G6PD) deficiency. However, these mechanisms are not involved in most cases of this hyperbilirubinemia. Additional plausible mechanisms for G6PD deficiency-associated hyperbilirubinemia need to be considered. Glutathione S-transferases (GST) activity depends on a steady quantity of reduced form of glutathione (GSH). If GSH is oxidized, it is reduced back by glutathione reductase, which requires the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH). The main source of NADPH is the pentose phosphate pathway, in which G6PD is the first enzyme. Rat kidney GSH, rat liver GST, and human red blood cell GST levels have been found to positively correlate with G6PD levels in their respective tissues. As G6PD is expressed in hepatocytes, it is expected that GST levels would be significantly decreased in hepatocytes of G6PD-deficient neonates. As hepatic GST binds bilirubin and prevents their reflux into circulation, hypothesis that decreased GST levels in hepatocytes is an additional mechanism contributing to G6PD deficiency-associated hyperbilirubinemia seems plausible. Evidence for and against this hypothesis are discussed in this article hoping to stimulate further research on the role of GST in G6PD deficiency-associated hyperbilirubinemia.

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Distribution of selected gene polymorphisms of UGT1A1 in a Saudi population

Cited by 11 publications

References 29 publications

Analysis of 12 variants in the development of gastric and colorectal cancers

Analysis of 12 variants in the development of gastric and colorectal cancers

Prevalence of the UGT1A1*6 (c.211G>A) Polymorphism and Prediction of Irinotecan Toxicity in Iranian Populations of Different Ethnicities

Decreased Glutathione S-transferase Level and Neonatal Hyperbilirubinemia Associated with Glucose-6-phosphate Dehydrogenase Deficiency: A Perspective Review

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