Association of POL1, MALT1, MC4R, PHLPP and DSEL single nucleotide polymorphisms in chromosome 18q region with type 2 diabetes in Tunisians

- Chromosome 18q21.1-23 was linked with type 2 diabetes and diabetic nephropathy.
- Candidate chromosome 18 loci: rs488846, rs2874116, rs1942872, rs9958800, rs9966483
- Only POL1 rs488846 and MC4R rs1942872 were associated with T2DM in Tunisians.
- Chromosome 18q variants play a role in T2DM pathogenesis, but not DN in Tunisians.

Previous studies and replication analyses have linked chromosome 18q21.1-23 with type 2 diabetes (T2DM) and its complications, including diabetic nephropathy (DN). Here we investigated the association of POL1-nearby variant rs488846, MALT1-nearby variant rs2874116, MC4R-nearby variant rs1942872, PHLPP rs9958800 and DSEL-nearby variant rs9966483 single nucleotide polymorphisms (SNPs) in the 18q region, previously linked with DN in African-Americans, with T2DM in (North African) Tunisian subjects, followed by their association with DN, which was performed subsequent to the analysis of the association with T2DM. Study subjects comprised 900 T2DM cases and 748 normoglycemic control, and genotyping was carried out by PCR-RFLP analysis. Of the 5 SNPs analyzed, POL1-nearby variant rs488846 [P = 0.044], and MC4R-nearby variant rs1942872 [P = 0.012] were associated with moderate risk of T2DM. However, there was a lack of consistency in the association of the 5 tested SNPs with DN. As such, it appears that the three chromosome 18q region variants appear to play a role in T2DM pathogenesis, but not with DN in North African Tunisian Arabs.