Crem Variant Rs17583959 Conferred Susceptibility To T1d Risk In The Tunisian Families

Type 1 diabetes mellitus (T1D) is a chronic autoimmune disease caused by the destruction of insulin-producing pancreatic beta-cells by autoreactive T cells. Studies in animal models, such as the non-obese diabetic (NOD) mouse reveal that this disease is under the control of several genes that encode molecules implicated in regulation of transcription factors and in T cell activation. In order to underline the role of the genes involved in this regulation pathways, we investigated, using the Sequenom MassARRAY platform, 13 single-nucleotide polymorphisms (SNPs) belonging to CREM, IRF5, STAT4, and STAT5a/ b genes in 59 T1D Tunisian families.By using the Family-based association test (FBAT), we identified an overtransmission of alleles/ genotype from parents to affected child at rs17583959 variant of CREM gene (allele G; Z score = 2.27; p = 0.02; Genotype GG: Z score = 1.96; p = 0.04) of CREM gene. When haplotypes were constructed between CREM variants, AGA haplotype (H2) was significantly over-transmitted from parents to affected offspring (Z score = 2.988; P = 0.002) and may confer a risk for T1D. Whereas, AAG haplotype (H5) (Z score = -2.000; p = 0.045) was less transmitted than expected to affected children suggesting its protective effect against T1D pathology.In conclusion, this study shows an eventually involvement of CREMgene in the risk for T1D in Tunisian families. Further researches of association and functional analysis across populations are needed to confirm these findings.