Protective Role of The SIGLEC14 Null Allele Against Type 2 Diabetes Mellitus: Evidence From an Egyptian Case-Control...

Chronic inflammation plays a central role in the pathogenesis of type 2 diabetes mellitus (T2DM), with emerging evidence highlighting the regulatory role of sialic acid-binding immunoglobulin-like lectins (SIGLECs). The SIGLEC-14 null polymorphism, resulting in reduced pro-inflammatory signalling, may influence susceptibility to T2DM. This study aimed to investigate the association between the SIGLEC-14 deletion polymorphism and the risk of T2DM and its related complications in an Egyptian population.

A case-control study was conducted on 194 participants, including 94 T2DM patients and 100 matched healthy controls. Genotyping of SIGLEC-14, SIGLEC-5, and the SIGLEC-14/5 fusion gene was performed using polymerase chain reaction (PCR). Clinical, biochemical, and demographic parameters were assessed. Associations between genotypes, alleles, and disease risk were evaluated using the chi-square test and odds ratios (ORs) with 95% confidence intervals (CIs).

The WT/WT genotype was significantly more frequent in T2DM patients, whereas the NULL/NULL genotype was less prevalent (P = 0.01). Carriers of the NULL/NULL genotype showed significantly reduced odds of T2DM (OR = 0.105, 95% CI: 0.012-0.864, P = 0.01). The NULL allele was associated with a lower risk of T2DM (OR = 0.40, 95% CI: 0.22-0.71, P = 0.001). Dominant and recessive models confirmed this protective effect (P = 0.008 and P = 0.02, respectively). NULL allele carriers had significantly lower BMI (P = 0.001) and reduced total cholesterol and LDL levels (P ≤ 0.034). No significant association was found between the SIGLEC14 deletion polymorphism and diabetic complications (P > 0.05).

The SIGLEC14 null allele is associated with reduced susceptibility to T2DM, potentially through the modulation of inflammatory pathways, but does not significantly influence disease complications. These findings highlight the role of immune-regulatory genetic variants in T2DM pathogenesis.