[Study of functional L1 retrotransposon in human type 2 diabetes susceptibility loci].

OBJECTIVE: To investigate the susceptibility gene of type 2 diabetes mellitus (T2DM) through a novel strategy. METHODS: Firstly, the common feature of the putative susceptibility genes in the reported susceptibility loci was searched by using NCBI BLAST, and a functional L1 retrotransposon in the loci was found. Secondly, the mRNA expression level of the functional L1 retrotransposon in 25 Han T2DM patients and 22 normal controls was investigated by reverse transcription-polymerase chain reaction, and statistical analysis was implemented in statistical package SPSS10.0. Thirdly, L1 retrotransponson genome mutation screening was performed via sequencing. RESULTS: Screening the human genome for the retrotransposon genome via alignment with the L1 genome using NCBI BLAST showed the functional L1 retrotransposons distribute on most chromosomes except for chromosomes 19, 21 and Y on which rare type 2 diabetes susceptibility loci were reported to reside, and their distribution sites are consistent with the locations of the reported candidate type 2 diabetes susceptibility loci. The mRNA expression level of the functional L1 retrotransposon in the T2DM patients was significantly lower than that in normal subjects (P<0.001). Nonsense mutations including deletion and/or point mutations were observed in all of the 6 T2DM patients tested, but no mutation was observed in all of the 4 normal controls tested. CONCLUSION: The functional L1 retrotransposon may be a candidate susceptibility gene of type 2 diabetes or a key regulator of the susceptibility genes, and it may be an ideal candidate biomarker for screening type 2 diabetes.