Association between donor and recipient TCF7L2 gene polymorphisms and the risk of new-onset diabetes mellitus after liver transplantation in a Han Chinese population

Ling, Qi; Xie, Haiyang; Lu, Di; Wei, Xuyong; Gao, Feng; Zhou, Lin; Xu, Xiao

doi:10.1016/j.jhep.2012.09.025

Cited by 67 publications

(59 citation statements)

References 37 publications

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“…Variables with statistical significance in univariate analysis were entered into a stepwise multivariate regression analysis. The predictive models were subsequently established, the risk scores and probability of HD were calculated as described previously (Ling et al, 2013). Hapoview software and SNPStats web tool (http://bioinfo.iconcologia.net/snpstats/start.…”

Section: Discussionmentioning

confidence: 99%

“…Applied Biosystems SNaP-Shot and TaqMan technology were applied to identify genetic polymorphism. The detailed procedure has been described previously (Ling et al, 2013).…”

Section: Genotypingmentioning

confidence: 99%

“…It can directly bind to multiple gluconeogenesis associated genes and involve in the hepatic glucose metabolism (Norton et al, 2011;Oh et al, 2012). Because different types of diabetes usually share genetic similarities (Cervin et al, 2008;Garcia-Compean et al, 2009), TCF7L2 has been reported to be associated with latent autoimmune diabetes in adult (LADA) (Lukacs et al, 2012) and new-onset diabetes after transplantation (NODAT) (Kurzawski et al, 2011;Ling et al, 2013), it is hypothesized that there is a potential link between the type 2 diabetes susceptibility genes and HD.…”

Section: Introductionmentioning

confidence: 99%

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Impacts of TCF7L2 gene polymorphisms on the susceptibility of hepatogenous diabetes and hepatocellular carcinoma in cirrhotic patients

Ling

Dong

Geng

et al. 2013

Gene

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Section: Discussionmentioning

confidence: 99%

“…Applied Biosystems SNaP-Shot and TaqMan technology were applied to identify genetic polymorphism. The detailed procedure has been described previously (Ling et al, 2013).…”

Section: Genotypingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Impacts of TCF7L2 gene polymorphisms on the susceptibility of hepatogenous diabetes and hepatocellular carcinoma in cirrhotic patients

Ling

Dong

Geng

et al. 2013

Gene

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“…In our previous single‐centre study, the incidence of NODAT was 20% of liver recipients during the first post‐transplant year and more than 85% occurred within 6 months; potential risk factors were recipient advanced age, high blood tacrolimus level, donor fatty liver and donor diabetes‐susceptibility gene variant . In another single‐centre study from Mainland China, NODAT was reported in 15% of recipients receiving living donor LT and 64% developed within 3 months; recipient increased age and high BMI were possible risk factors .…”

mentioning

confidence: 83%

New‐onset diabetes after liver transplantation: a national report from China Liver Transplant Registry

Ling

Xie

et al. 2016

Liver International

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“…33,34,37 The TCF7L2 SNP rs7903146 is an exception to this; rs7903146 variants have been associated with NODAT in Korean 45 (P=0.02), white European 44 (P=0.002), and Polish Caucasian 43 (P=0.02) populations, although not all reports demonstrate an association. 34,97,98 This study had a comparable cohort size and rs7903146 minor allele frequency to the other studies but did not find an association between rs7903146 and NODAT. This may reflect the use of an extreme NODAT phenotype, which could prevent identification of genetic variants associated with milder disease.…”

Section: Strengths and Limitationsmentioning

confidence: 62%

Genetics of New-Onset Diabetes after Transplantation

McCaughan

McKnight²,

Maxwell

2014

Journal of the American Society of Nephrology

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New-onset diabetes after transplantation is a common complication that reduces recipient survival. Research in renal transplant recipients has suggested that pancreatic b-cell dysfunction, as opposed to insulin resistance, may be the key pathologic process. In this study, clinical and genetic factors associated with new-onset diabetes after transplantation were identified in a white population. A joint analysis approach, with an initial genome-wide association study in a subset of cases followed by de novo genotyping in the complete case cohort, was implemented to identify single-nucleotide polymorphisms (SNPs) associated with the development of new-onset diabetes after transplantation. Clinical variables associated with the development of diabetes after renal transplantation included older recipient age, female sex, and percentage weight gain within 12 months of transplantation. The genome-wide association study identified 26 SNPs associated with new-onset diabetes after transplantation; this association was validated for eight SNPs (rs10484821, rs7533125, rs2861484, rs11580170, rs2020902, rs1836882, rs198372, and rs4394754) by de novo genotyping. These associations remained significant after multivariate adjustment for clinical variables. Seven of these SNPs are associated with genes implicated in b-cell apoptosis. These results corroborate recent clinical evidence implicating b-cell dysfunction in the pathophysiology of newonset diabetes after transplantation and support the pursuit of therapeutic strategies to protect b cells in the post-transplant period. One-year graft survival after renal transplantation is now excellent, exceeding 93% for organs donated after brain death and 96% for those from living donors. 1-3 Technical advancements in surgery, improved understanding of immunology, and innovative developments in pharmacology have altered the landscape of renal transplantation. The goal of preventing early graft loss has largely been achieved and arguably the greatest challenge now is the avoidance of late graft failure. Although there has been a considerable improvement in 1-year renal transplant survival, the rate of graft attrition after the first year remains frustratingly constant. 2,4 New-onset diabetes after transplantation (NODAT) is a common and serious disorder that curtails recipient survival. [5][6][7] NODAT is associated with cardiovascular complications [8][9][10][11] and develops in 2%-50% 12 of renal transplant recipients. Approximately 50% of recipients with NODAT require insulin therapy. [6][7][8][13][14][15] A number of clinical variables have been associated with NODAT, including black ethnicity, older recipient age, female sex, obesity, immunosuppression, and viral infections. 5,6,8,13,16,17 Until recently, the pathophysiology of NODAT was considered to be analogous to type 2 diabetes mellitus. Renal transplant recipients have increased insulin resistance compared with transplant-naïve persons with normal renal function. 18 In a nondiabetic renal transplant population, the m...

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Association between donor and recipient TCF7L2 gene polymorphisms and the risk of new-onset diabetes mellitus after liver transplantation in a Han Chinese population

Cited by 67 publications

References 37 publications

Impacts of TCF7L2 gene polymorphisms on the susceptibility of hepatogenous diabetes and hepatocellular carcinoma in cirrhotic patients

Impacts of TCF7L2 gene polymorphisms on the susceptibility of hepatogenous diabetes and hepatocellular carcinoma in cirrhotic patients

New‐onset diabetes after liver transplantation: a national report from China Liver Transplant Registry

Genetics of New-Onset Diabetes after Transplantation

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