Interaction of iron status with single nucleotide polymorphisms on incidence of type 2 diabetes

PLoS One. 2017 Apr 13;12(4):e0175681. doi: 10.1371/journal.pone.0175681. eCollection 2017.

Abstract

The objective of this study is to find single nucleotide polymorphisms (SNPs) associated with a risk of Type 2 diabetes (T2D) in Korean adults and to investigate the longitudinal association between these SNPs and T2D and the interaction effects of iron intake and average hemoglobin level. Data from the KoGES_Ansan and Ansung Study were used. Gene-iron interaction analysis was conducted using a two-step approach. To select candidate SNPs associated with T2D, a total of 7,935 adults at baseline were included in genome-wide association analysis (step one). After excluding T2D prevalent cases, prospective analyses were conducted with 7,024 adults aged 40-69 (step two). The association of selected SNPs and iron status with T2D and their interaction were determined using a Cox proportional hazard model. A total of 3 SNPs [rs9465871 (CDKAL1), rs10761745 (JMJD1C), and rs163177 (KCNQ1)] were selected as candidate SNPs related to T2D. Among them, rs10761745 (JMJD1C) and rs163177 (KCNQ1) were prospectively associated with T2D. High iron intake was also prospectively associated with the risk of T2D after adjusting for covariates. Average hemoglobin level was positively associated with T2D after adjusting for covariates in women. We also found significant interaction effects between rs10761745 (JMJD1C) and average hemoglobin levels on the risk of T2D among women with normal inflammation and without anemia at baseline. In conclusion, KCNQ1 and JMJD1C may prospectively contribute to the risk of T2D incidence among adults over the age of 40 and JMJD1C, but CDKAL1 may not, and iron status may interactively contribute to T2D incidence in women.

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Asian People / genetics
  • Diabetes Mellitus, Type 2 / epidemiology*
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / metabolism
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Hemoglobins / metabolism
  • Humans
  • Incidence
  • Iron / metabolism*
  • Jumonji Domain-Containing Histone Demethylases / genetics*
  • KCNQ1 Potassium Channel / genetics*
  • Male
  • Middle Aged
  • Oxidoreductases, N-Demethylating / genetics*
  • Polymorphism, Single Nucleotide*
  • Prospective Studies
  • Republic of Korea / epidemiology
  • Sex Factors
  • tRNA Methyltransferases / genetics*

Substances

  • Hemoglobins
  • KCNQ1 Potassium Channel
  • KCNQ1 protein, human
  • Iron
  • JMJD1C protein, human
  • Jumonji Domain-Containing Histone Demethylases
  • Oxidoreductases, N-Demethylating
  • tRNA Methyltransferases
  • CDKAL1 protein, human

Grants and funding

This research was supported by a fund (HD14B0005) by Research of Korea Centers for Disease Control and Prevention and supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI16C2048). This study was provided with biospecimens and data from the Korean Genome Analysis Projects (4845-301), the Korean Genome and Epidemiology (4845-302), and Korea Biobank Project (4851-307, KBP-2014-000), which were supported by the Korea Centers for Disease Control & Prevention, Republic of Korea. The funders had no role in study design, data analysis, decision to publish, or preparation of the manuscript.