Association of PPARγ (rs1801282) and TCF7L2 (rs7903146) gene polymorphisms and susceptibility of Type 1 diabetes mellitus in Egyptian children.

Type 1 diabetes mellitus (T1DM) is caused by the autoimmune depletion of β-cells. Non-HLA genes notably peroxisome proliferator-activated receptor gamma (PPARγ) and transcription factor 7-like 2 (TCF7L2)-important regulators of insulin sensitivity and secretion-may affect risk even though HLA loci predominate in heredity. However, their synergistic impact in T1DM are yet unknown, especially in Egyptian children. So, PPARγ (Pro12Ala, rs1801282 C/G) and TCF7L2 (rs7903146 C/T) polymorphisms were examined in relation to T1DM risk in Egyptian children. Ninety-five normal subjects and one hundred T1DM patients were included. The amplification-refractory mutation system-polymerase chain reaction (ARMS-PCR) utilized to genotype these single nucleotide polymorphisms. T1DM patients exhibited higher HbA1c (11.09 ± 2.46% vs. controls 5.04 ± 0.18%; P < 0.001), while there were no the demographic disparities across the groups (P > 0.05 for age, sex, and BMI). There was a strong correlation found between T1DM and the PPARγ rs1801282 variant. The T1DM group had a significantly greater heterozygous CG genotype (10.0%) than controls (1.1%) (OR = 10.44; P = 0.01). Furthermore, patients had a considerably higher minor G allele frequency (12.0% vs. 6.0%; OR = 2.22; P = 0.04), suggesting a greater risk to this condition. Reciprocally, the CC genotype provided protection from T1DM (OR = 0.32; P = 0.03). The TCF7L2 rs7903146 variant, on the other hand, did not show any significant discrepancies in the groups' genotype or allele frequencies. TCF7L2 rs7903146 fails to rise predisposition to T1DM in Egyptian children, however the PPARγ rs1801282 CG genotype and G allele do. Such outcomes point to a possible involvement of PPARγ in the pathophysiology of T1DM.