Page 93 - EJMO-9-1

Eurasian Journal of Medicine and
Oncology
T2D polymorphisms in Asians

Figure 4. SNPs associated with therapeutic responses to antidiabetic drugs. The IGF2BP2 rs4402960 T allele is associated with a good response to
repaglinide but does not show a similar effect with pioglitazone. A similar pattern is observed with the TCF7L2 rs7903146 T allele, which demonstrates a
good response to biguanides but a poor response to sulfonylureas. In contrast, the IGF2BP2 rs1470579 C allele is linked to a poor response to metformin.
The TCF7L2 rs12255372 T allele is associated with negative responses to sulfonylureas. The KCNQ1 rs2237892 C allele exhibits non-responsiveness to
both repaglinide and gliclazide, whereas the KCNQ1 rs2237895 C allele is associated with a positive response to gliclazide. In addition, the SLC30A8
rs13266634 C allele shows a poor response to repaglinide, while the KCNJ11 rs5219 T allele is linked to a positive response to metformin.
Abbreviations: TCF7L2: Transcription factor-7–like 2; IGF2BP2: Insulin-like growth factor 2 mRNA-binding protein 2; PPARγ: Peroxisome proliferator-
activated receptor gamma; SLC30A8: Solute carrier family 30-member 8; KCNJ11: Potassium inwardly rectifying channel subfamily J member 11;
KCNQ1: Potassium voltage-gated channel subfamily Q member 1; SNPs: Single nucleotide polymorphisms.

Table 2. SNPs associated with therapeutic response to antidiabetic drugs

Genes SNPs Risk allele Drug Phenotype References
IGF2BP2 rs4402960 T Repaglinide Drug response↑ 72
IGF2BP2 rs4402960 T Pioglitazone Drug response↓ 71
IGF2BP2 rs1470579 C Repaglinide Drug response↓ 72
KCNJ11 rs5219 T Metformin Drug response↑ 81
KCNQ1 rs2237892 C Repaglinide Drug response↓ 77
KCNQ1 rs2237892 C Gliclazide Drug response↓ 78
KCNQ1 rs2237895 C Gliclazide Drug response↑ 78
SLC30A8 rs13266634 C Repaglinide Drug response↓ 83
TCF7L2 rs12255372 T Sulfonylurea Drug response↓ 76
TCF7L2 rs7903146 T Metformin Drug response↑ 73
TCF7L2 rs7903146 T Sulfonylurea Drug response↓ 98
Notes: ↑: Increase; ↓: Decrease.
Abbreviations: IGF2BP2: Insulin-like growth factor 2 mRNA-binding protein 2; KCNJ11: Potassium inwardly rectifying channel subfamily J member
11; KCNQ1: Potassium voltage-gated channel subfamily Q member 1; SLC30A8: Solute carrier family 30-member 8; TCF7L2: Transcription factor-7–
like 2.

The KCNQ1 rs2237892 C allele demonstrates non- potassium channels. Further investigation is needed to
responsiveness to both non-sulfonylurea secretagogues determine how these SNPs influence drug response.
and sulfonylureas. 77,78 In contrast, the KCNQ1 rs2237895 The KCNJ11 rs5219 T allele is linked to a positive
C allele is associated with a favorable response to response to biguanides. This gene encodes the Kir6.2
81
sulfonylureas. However, gene expression studies have not subunit of the K channel in pancreatic β-cells, which
78
ATP
investigated the KCNQ1 rs2237892 C allele or rs2237895 C plays a crucial role in the synthesis and secretion of insulin,
allele in the pancreas. Instead, the focus has been on whole both essential for maintaining normal blood glucose levels.
blood and adipose tissue. 79,80 As a result, these findings These processes involve a series of intricate steps regulated
do not reflect pancreatic pathology, particularly KCNQ1- by various genes. Among these, certain genes have been
regulated insulin secretion influenced by low-voltage-gated identified as being associated with T2D due to specific

Volume 9 Issue 1 (2025) 85 doi: 10.36922/ejmo.7549