Open AccessThe variant at TGFBRAP 1 is significantly associated with type 2 diabetes mellitus and affects diabetes‐related mi RNA expression
Author(s) -
Yang Song,
Chen Xiaotian,
Yang Mengyao,
Zhao Xianghai,
Chen Yanchun,
Zhao Hailong,
Liu Chunlan,
Shen Chong
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13885
Subject(s) - diabetes mellitus , rna , type 2 diabetes mellitus , type 1 diabetes , medicine , biology , endocrinology , biochemistry , gene
While the transforming growth factor‐β1 ( TGF ‐β1) regulates the growth and proliferation of pancreatic β‐cells, its receptors trigger the activation of Smad network and subsequently induce the insulin resistance. A case‐control was conducted to evaluate the associations of the polymorphisms of TGF ‐β1 receptor‐associated protein 1 ( TGFBRAP 1 ) and TGF ‐β1 receptor 2 ( TGFBR 2 ) with type 2 diabetes mellitus (T2 DM ), and its genetic effects on diabetes‐related mi RNA expression. mi RNA microarray chip was used to screen T2 DM ‐related mi RNA and 15 differential expressed mi RNA s were further validated in 75 T2 DM and 75 normal glucose tolerance ( NGT ). The variation of rs2241797 (T/C) at TGFBRAP 1 showed significant association with T2 DM in case‐control study, and the OR (95% CI ) of dominant model for cumulative effects was 1.204 (1.060‐1.370), Bonferroni corrected P < 0.05. Significant differences in the fast glucose and HOMA ‐β indices were observed amongst the genotypes of rs2241797. The expression of has‐miR‐30b‐5p and has‐miR‐93‐5p was linearly increased across TT , TC , and CC genotypes of rs2241797 in NGT , P trend values were 0.024 and 0.016, respectively. Our findings suggest that genetic polymorphisms of TGFBRAP 1 may contribute to the genetic susceptibility of T2 DM by mediating diabetes‐related mi RNA expression.