Ecotoxicology and Environmental Safety (Oct 2024)

Genetic predisposition to impaired beta-cell function modifies the association between serum pyrethroid levels and the risk of type 2 diabetes: A gene-environment interaction study

  • Chengyong Jia,
  • Shiyang Zhang,
  • Jun An,
  • Xu Cheng,
  • Peiwen Li,
  • Xin Zhang,
  • Tingting Geng,
  • Wending Li,
  • Yan Yan,
  • Zhuoya Zhao,
  • Handong Yang,
  • Kun Yang,
  • Tao Jing,
  • Huan Guo,
  • Xiaomin Zhang,
  • Tangchun Wu,
  • Meian He

Journal volume & issue
Vol. 284
p. 116948

Abstract

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Previous studies suggested that pyrethroid exposure was associated with elevated type 2 diabetes (T2D) risk, while it remains uncertain whether genetic predisposition modifies this association. A nested case-control study within the prospective Dongfeng-Tongji cohort comprised 1832 T2D cases, age- (±5 years) and sex-matched controls with qualified genotyping data. Serum pyrethroids were measured by gas chromatography-tandem mass spectrometry. Overall diabetes-related genetic risk score (GRS) or pathway-specific GRS, including unweighted GRSs (uGRS) and weighted GRSs (wGRS), was developed by genetic variants identified in Asian populations. Higher overall diabetes-related GRS and GRS specific to the pathway of impaired beta cell function (Beta-cell GRS) were associated with a higher incident T2D risk. Beta-cell uGRS significantly modified the association of serum permethrin (Pinteraction=0.04) and deltamethrin (Pinteraction=0.01) with T2D. Specifically, for each doubling increase in serum deltamethrin, the odds ratios (ORs) (95 % confidence intervals [CIs]) for T2D were 1.23 (0.98–1.56) and 0.91 (0.77–1.07) in the highest and lowest Beta-cell uGRS group, as well as 1.23 (1.02–1.47) and 0.95 (0.78–1.15) for Beta-cell wGRS group, respectively. When considering jointly, those with the highest deltamethrin levels and highest Beta-cell GRS had a substantially higher T2D risk, compared with the reference group (OR for uGRS: 3.79 [95 % CI: 2.03–7.07], Pinteraction=0.03 and 3.23 [95 % CI: 1.78–5.87], Pinteraction=0.05 for wGRS). Our findings suggested that genetic susceptibility to impaired beta-cell function should be considered for T2D prevention targeting pyrethroid exposure, particularly deltamethrin.

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