Biotechnological Assessment of SLC47A2 Genetic Variations and Glycemic Control in Diabetes Mellitus

Type 2 Diabetes Mellitus (T2DM) is a multifactorial metabolic disorder influenced by genetic and environmental factors. Glycemic Control (GC) plays a key role in preventing diabetes-related complications. Variations in drug transporter genes such as SLC47A2 may contribute to differences in GC among patients receiving metformin therapy.

A cross-sectional study was conducted on 120 T2DM patients receiving metformin monotherapy. GC was evaluated using Fasting Blood Glucose (FBG), HbA1c%, insulin levels, HOMA-IR, and insulin sensitivity indices. Participants were categorized into good and poor GC groups based on ADA criteria. Six SLC47A2 SNPs (rs553096515, rs566505112, rs535426224, rs557659793, rs183037055, rs540311235) were genotyped using PCR and DNA sequencing. Statistical analyses included allele/genotype frequencies, Hardy–Weinberg Equilibrium (HWE), Linkage Disequilibrium (LD), haplotype structure, and SNP–SNP interaction.

Overall, 55% of participants had poor GC. FBG and HbA1c% were significantly higher in the poor GC group (p < 0.05). Novel alleles were identified in three SNPs. No significant associations were found between any of the six SNPs and GC status. Most SNPs showed significant deviations from HWE. LD analysis demonstrated a strong linkage among rs553096515, rs566505112, and rs535426224 in both GC groups.

Although multiple SLC47A2 variants and novel alleles were detected, none showed a significant relationship with GC. Strong LD among selected SNPs suggests possible shared genetic patterns, yet without an impact on glycemic status. Factors beyond SLC47A2 variation may play more influential roles in determining GC among Iraqi T2DM patients.

SLC47A2 gene variants were not significantly associated with glycemic control in T2DM patients treated with metformin. Broader genetic assessments and larger sample sizes are recommended for future research.