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. 2012;7(4):e34895.
doi: 10.1371/journal.pone.0034895. Epub 2012 Apr 11.

Associations of type 2 diabetes with common variants in PPARD and the modifying effect of vitamin D among middle-aged and elderly Chinese

Ling Lu  1 , Ying Wu, Qibin Qi, Chen Liu, Wei Gan, Jingwen Zhu, Huaixing Li, Xu Lin
Affiliations

Associations of type 2 diabetes with common variants in PPARD and the modifying effect of vitamin D among middle-aged and elderly Chinese

Ling Lu et al. PLoS One. 2012.

Abstract

Background: Previous studies have identified that variants in peroxisome proliferator-activated receptor PPAR-δ (PPARD), a target gene of vitamin D, were significantly associated with fasting glucose and insulin sensitivity in European populations. This current study sought to determine (1) whether the genetic associations of PPARD variants with type 2 diabetes and its related traits could be replicated in Chinese Han population, and (2) whether the associations would be modified by the effect of vitamin D status.

Methods and findings: We genotyped 9 tag single nucleotide polymorphisms (SNPs) that cover the gene of PPARD (rs2267664, rs6902123, rs3798343, rs2267665, rs2267668, rs2016520, rs2299869, rs1053049, and rs9658056) and tested their associations with type 2 diabetes risk and its related traits, including fasting glucose, insulin and HbA1c in 3,210 Chinese Hans. Among the 9 PPARD tag SNPs, rs6902123 was significantly associated with risk of type 2 diabetes (odds ratio 1.75 [95%CI 1.22-2.53]; P = 0.0025) and combined type 2 diabetes and impaired fasting glucose (IFG) (odds ratio 1.47 [95%CI 1.12-1.92]; P = 0.0054). The minor C allele of rs6902123 was associated with increased levels of fasting glucose (P = 0.0316) and HbA1c (P = 0.0180). In addition, we observed that vitamin D modified the effect of rs6902123 on HbA1c (P for interaction = 0.0347).

Conclusions/significance: Our findings demonstrate that common variants in PPARD contribute to the risk of type 2 diabetes in Chinese Hans, and provided suggestive evidence of interaction between 25(OH)D levels and PPARD-rs6902123 on HbA1c.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Interaction between PPARD-rs6902123 and plasma 25-hydroxyvitamin D levels on HbA1c.
The means (SE) of HbA1c by PPARD-rs6902123 genotypes according to quartiles of plasma 25-hydroxyvitamin D concentrations were calculated in 2943 subjects, with adjustment for age, sex, geographic region (Beijing and Shanghai) and BMI (P for interaction = 0.0347). Participants with known diabetes or using glucose-lowering treatment were excluded. C allele carriers (black) had significant higher HbA1c concentrations than TT carriers (gray) (P = 0.0172) in the lowest group of 25-hydroxyvitamin D, but not in the other groups (P≥0.0814).
See this image and copyright information in PMC

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