Significant Association of TGF-Beta1 C-T Transition in Codon 10 of the Gene with Posttransplant Diabetes

Abstract

Post-transplant Diabetes (PTD) is a serious complication of transplantation. We hypothesize that transforming growth factor-beta (TGF-β1), a multifunctional growth factor which plays a key role in the development of tissue fibrosis, may be involved in the pathophysiology of PTD. Our purpose was to examine the functional polymorphism within the TGF-β1 gene in codons 10 of promoter region of the gene association with Kuwaiti PTD post kidney transplantation. Method: We conducted a large case-control study using cases with kidney transplantation who have developed diabetes post transplantation, 152. Controls were renal recipient patients who did not present diabetes a year post-kidney transplantation, 150. Neither cases nor controls had previous history of diabetes. Genotyping was by amplification refractory mutation system polymerase chain reaction. Fisher’s exact test was used to analyze the data. Our diagnosis criteria incorporated with the international consensus guidelines regarding the definition of PTD. Results: There was a significant difference in the frequency of the TGF-β1 codon 10 genotype in the PTD cases compared with controls. There were neither gender nor age at onset specificity statistical differences among the PTD cohort compared to non-PTD cohort. Individual with the TT (TGF- β1 gene in codons 10) was strongly susceptible to PTD (p=0.001); whereas, the CC of the same gene showed protection against PTD progression. Although T allele was strongly associated with progression of PTD, p=1.4 * 10-5, it could not exert its impact during CT genotype, p=0.6. Discussion: In our study the TGF-β1 codon 10 polymorphism is associated with PTD post-kidney transplantation. Variation in this gene may contribute to the genetic predisposition to this complication in kidney transplantation. Further subgroup analyses are underway to find out if there is any correlation between bone mass indexes, familial history of diabetes, hepatitis C infection among both cohorts. Disclosure M.M.J. Jahromi: None.