MAP3K1 May be a Promising Susceptibility Gene for Type 2 Diabetes Mellitus in an Iranian Population

Document Type : Original Article

Authors
Shahram Torkamandi 1
Milad Bastami 2
Hamid Ghaedi 1
Fateme Moghadam 3
Reza Mirfakhraie 1
Mir Davood Omrani 1
1 Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2 Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
3 Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Abstract
Considering that MAPK (mitogen- activated protein kinase) signaling pathway has an important role in the
progression of inflammatory cytokine secretion in type 2 diabetes mellitus (T2DM), we have recently
investigated the reported genetic polymorphism from genome wide association study in MAP3K1 (mitogen- activated protein kinase kinase kinase 1) in diabetes as an important member of MAPK signaling. This study
aimed to investigate the possible association of rs10461617 at the upstream of MAP3K1 gene in an Iranian case- control study with the risk of T2DM. The study population was comprised of 342 unrelated Iranian individuals
including 177 patients with T2DM and 165 unrelated healthy control subjects. Genotyping was performed using
PCR-RFLP and confirmed with sequencing. In a logistic regression analysis, the rs10461617A allele was
associated with a significantly higher risk of T2DM assuming the log- additive model (OR: 1.44, 95% CI: 1.01-
2.05, P = 0.039). In conclusion, we provided the first evidence for the association of rs10461617 at the upstream
of MAP3K1 with the risk of T2DM in an Iranian population.
Keywords
Type 2 diabetes mellitus
genome- wide association study
MAP3K1
cytokines