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.
Ecotoxicol Environ Saf
; 284: 116948, 2024 Oct 01.
Article
in En
| MEDLINE
| ID: mdl-39205355
ABSTRACT
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) (95â¯% 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 [95â¯% CI 2.03-7.07], Pinteraction=0.03 and 3.23 [95â¯% 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pyrethrins
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Genetic Predisposition to Disease
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Diabetes Mellitus, Type 2
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Insulin-Secreting Cells
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Gene-Environment Interaction
Limits:
Adult
/
Aged
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Female
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Humans
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Male
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Middle aged
Country/Region as subject:
Asia
Language:
En
Journal:
Ecotoxicol Environ Saf
/
Ecotoxicol. environ. saf
/
Ecotoxicology and environmental safety
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
Países Bajos