Genetic variants and haplotypes of the UGT1A9, 1A7 and 1A1 genes in Chinese Han

Zhang, Xiaoqing; Ao, Guokun; Wang, Yuewen; Wei, Yan; Wang, Min; Chen, Erfei; Yang, Fangfang; Yang, Jin

doi:10.1590/s1415-47572012005000036

Cited by 11 publications

(7 citation statements)

References 36 publications

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“…Selection of SNPs was done based on their association with serum bilirubin levels as well as their prevalence in Asia population (Huang et al, 2005; Kang et al, 2010; Zhang et al, 2012; Dai et al, 2013; Chiddarwar et al, 2017). Finally, a total of 14 SNPs (10 of UGT1A1 and 4 of SLCO1B ) were selected.…”

Section: Methodsmentioning

confidence: 99%

Combined Effects of UGT1A1 and SLCO1B1 Variants on Chinese Adult Mild Unconjugated Hyperbilirubinemia

Bai

Luo

Liu³

et al. 2019

Front. Genet.

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The potential for genetic variation to cause adult unconjugated hyperbilirubinemia is increasingly being recognized. However, the cumulative effects of genetic variants have not been fully illuminated. The current study aimed to investigate the effects of uridine diphospho-glucuronosyl transferase 1A1 (UGT1A1) and/or solute carrier organic anion transporter family member 1B (SLCO1B) polymorphic variants and their combined effects on mild unconjugated hyperbilirubinemia in Chinese adults. Fourteen genetic variants in the UGT1A1 or SLCO1B gene were genotyped through sequencing in 148 adults with unconjugated hyperbilirubinemia and 158 healthy controls. Variants c.-3275T > G, (TA)6>(TA)7, c.211G > A or c.1091C > T within the UGT1A1 gene as well as c.521T > C within the SLCO1B1 gene appear to be genetic risk factors for inherited unconjugated hyperbilirubinemia. After adjusting for covariates, the results of multivariate logistic regressions revealed that odds ratios (ORs) [(with 95% confidence interval (CI)] of these five variants were 2.35 (95% CI: 1.37–4.01, p = 0.002), 2.38 (95% CI: 1.35–4.20, p = 0.003), 2.99 (95% CI: 1.71–5.21, p < 0.001), 7.60 (95% CI: 1.99–28.96, p = 0.003), and 2.54 (95% CI: 1.27–5.11, p = 0.009), respectively. The OR for unconjugated hyperbilirubinemia is positively correlated with the cumulative number of these five variants in adults. And the greater the number of genetic variations, the higher the total bilirubin level. Adults carrying diplotype 3/4 (homozygous c.-3275T > G and heterozygous (TA)6>(TA)7) had higher bilirubin levels than those with diplotypes 1/3 (heterozygous c.-3275T > G and (TA)6>(TA)7)) or 1/4 (heterozygous c.-3275T > G) (P < 0.05). Similarly, bilirubin levels in individuals with diplotype 2/4 (heterozygous c.-3275T > G and c.211G > A) were higher than adults carrying diplotypes 1/2 (heterozygous c.211G > A) or 1/4 (P < 0.001). For subjects with heterozygous or homozygous variant c.211G> A, as the number of c.521T > C alleles variation increased, the incidence of unconjugated hyperbilirubinemia increased, but it was not statistically significant. Our results indicate that variants of UGT1A1 and/or SLCO1B1 have combined effects on Chinese adult mild unconjugated hyperbilirubinemia.

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Section: Methodsmentioning

confidence: 99%

Combined Effects of UGT1A1 and SLCO1B1 Variants on Chinese Adult Mild Unconjugated Hyperbilirubinemia

Bai

Luo

Liu³

et al. 2019

Front. Genet.

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“… 69 A series reported the rate of *28 allelic frequency in the Chinese to be around 10.5%. 70 In a multiethnic study that included 39 Chinese subjects, the incidence of homozygosity of UGT1A1 ([TA]7/7) was found to be 8% in Chinese, 5% in Asians, and 13% in Caucasians. 71 …”

Section: Tolerability To Systemic Therapy For Colorectal Cancer In Asmentioning

confidence: 99%

Colorectal cancer in Chinese patients: current and emerging treatment options

B.Y.

2014

OTT

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Colorectal cancer is the second most common cancer in Hong Kong and its incidence is rising in economically developed Chinese cities, including Hong Kong and Shanghai. Several studies conducted in the People’s Republic of China have characterized the unique molecular epidemiology of familial colorectal cancer syndromes and molecular biomarkers such as microsatellite instability and genetic mutations (eg, KRAS, NRAS, BRAF, PIK3CA, ERCC1) in Chinese populations. Interethnic differences in anticancer drug response and toxicity have been well described in many cancers, and this review examined the literature with regard to the tolerance of Chinese patients to commonly used chemotherapeutic regimens and targeted therapies for metastatic colorectal cancer. Studies on the pharmacogenomic differences in drug metabolizing and DNA repair enzymes between Chinese, North Asians, and Caucasian patients were also reviewed.

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“…In other studies, UGT1A1*28 polymorphism was present in a lower percentage such as Y. Akiyama et al (2008) [11][12][13][14][15][16][17][18][19]. It is noteworthy that ethnic differences do exist in the UGT1A1*28 polymorphism, that's why there is differences between different studies of different ethnicities.…”

Section: Discussionmentioning

confidence: 88%

UGT1A1*28 polymorphism in advanced colorectal cancer: The story is not yet ended.

Bastawisy

El-Zeiny

Farid

et al. 2014

JCO

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516 Background: UGT1A1*28 polymorphism is associated with neutropenia and diarrhea in previous reports, this study tried to investigate correlation with other toxicities like vomiting. Methods: This is a prospective case control study including all eligible cases of advanced colorectal cancer. The genotypes of UGT1A1*28 was assessed in the peripheral blood and/or in tissues by PCR. Patients were divided into two groups, group 1—patients with no mutation, group 2—patients with homo or hetero mutation. All patients received standard IFL regimen. Primary endpoints were (1) comparison between the 2 groups as regard vomiting (2) assessement of the incidence of UGT1A1*28 polymorphism. Secondary endpoints were comparison between the 2 groups as regard: neutropenia, diarrhea, treatment delay, progressive diseases (PD), progression free survival (PFS), and overall survival (OS). Results: 46 cases of advanced colorectal cancer presenting to National Cancer Institute, Cairo University, aged between 19 and 71 years with a median age of 45 years were included and followed up during the period from September 2010 to January 2013 with a median follow up of 9 months. UGT1A1*28 polymorphism was present in 20 patients (43%) of them 15% are homozygous. Grade (2-4) vomiting was found in 8.3 % of group 1 versus 52.5 % of group 2. (p = 0.01). Grade (2-4) neutropenia were found in 20.8 % of group 1 versus 64.7 % of group2. (p = 0.03). Grade (2-4) diarrhea was found in 37.5 % of patients of group 1 and 27.5% of patients with group 2. (p = 0.75). Treatment delay occurred in 29.16 % of group 1 versus 72.4 % of group 2. (p = 0.02). 25% of group 1 showed PD versus 25 % of group 2. (p = 0.8). 1 year PFS was 19% in group 1 versus 23 % in group 2. (p = 0.8) while there was a trend towards better OS in group 1 (47 % versus % 35). (p = 0.07). Conclusions: UGT1A1*28 polymorphism is present frequently (43%) in a Caucasian population and is associated with more vomiting, neutropenia and treatment delay.

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Genetic variants and haplotypes of the UGT1A9, 1A7 and 1A1 genes in Chinese Han

Cited by 11 publications

References 36 publications

Combined Effects of UGT1A1 and SLCO1B1 Variants on Chinese Adult Mild Unconjugated Hyperbilirubinemia

Combined Effects of UGT1A1 and SLCO1B1 Variants on Chinese Adult Mild Unconjugated Hyperbilirubinemia

Colorectal cancer in Chinese patients: current and emerging treatment options

UGT1A1*28 polymorphism in advanced colorectal cancer: The story is not yet ended.

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