Genetic association of IDE, POU2F1, PON1, IL1α and IL1β with type 2 diabetes in Pakistani population.

A number of genes are known to be involved in glucose homeostasis. Mutations and polymorphisms in candidate genes may effect insulin production, action or resistance. This study was designed to report the association of genetic polymorphism with the type 2 diabetes (T2D) in Pakistani population. A total of 458 subjects (case n=288, control n=170) participated in the study. Nine single nucleotide polymorphisms were investigated in genes IDE (rs6583813 C>T, rs7910977 C>T), POU2F1 (rs3767434 A>T, rs10918682 A>T, rs2146727 A>G), WFS1 (rs734312 A>G), PON1 (rs854560 T>A), IL1α (rs1800587 C>T) and IL1β (rs1143634 C>T). Genotyping was performed by DNA sequencing after nested polymerase chain reaction of targeted regions. Results indicated that rs7910977 in IDE showed significant association with the development of T2D [P=0.012, OR 1.677 (95% CI 1.112-2.438)]. The rs10918682 in POU2F1 was associated with T2D [P<0.001, OR 3.606 (95% CI 2.165-6.005)]. The rs854560 in PON1 was associated with incidences of T2D and increased the risk of cardiovascular complications [P=0.031, OR 0.663 (95% CI 0.455-0.965)] in diabetics. The rs734312 from WFS1 gene was associated with diabetes at genotype level (P<0.01). Haplotype analysis of rs1800587-rs1143634 depicted CC haplotype increased the susceptibility to diabetes (P<0.05). Haplotype GAA from rs2146727-10918682-rs3767434 was protective against diabetes (P<0.01) and GGA exhibited the association with T2D (P<0.01). Haplotype CT from rs6583813-rs7910977 was protective against diabetes (P=0.02). Our study provided evidence to IDE, PON1, WFS1, POU2F1, IL1α and IL1β associated with T2D in Pakistanis.