DNA methylation in the association between pesticide exposures and type 2 diabetes

Table 1 Search strategy

Stage	Database	MeSH1/explode2		Title, abstract1/abstract, keywords2	Retrieval period
Stage 1	PubMed, EMBASE	“DNA methylation”	AND	“DNA methylations” OR “methylation DNA” OR “methylations DNA” OR “Methylations”	Up to January 2024
		“Pesticides”	AND	“Fungicide” OR “herbicide” OR “insecticide” OR “molluscicide” OR “rodenticide” OR “carbamate” OR “pyrethroid” OR “chlorinated hydrocarbon” OR “agricultural chemical” OR “organochlorine” OR “organophosphorus”
Stage 2		“Diabetes mellitus, type 2”	AND	“Diabetes mellitus noninsulin-dependent” OR “stable diabetes mellitus” OR “diabetes mellitus type ii” OR “diabetes mellitus maturity-onset” OR “maturity-onset diabetes mellitus” OR “diabetes mellitus slow onset” OR “type 2 diabetes mellitus” OR “diabetes mellitus adult-onset”	April 2017 to January 2024

¹Search terms used in PubMed.

²Search terms used in EMBASE.

MeSH: Medical subject headings.

Table 2 Genes whose methylation is involved in pesticide exposure and type 2 diabetes

Gene	Function	Pesticide exposure & DNA methylation1			DNA methylation & T2D2
		Type of pesticide	Methylation status	Location	Methylation status	Location
Alu	A member of the short interspersed repetitive DNA elements family of repetitive elements	Persistent organic pollutants	↓[32-35]	-	↓[49]	-
CABLES1	Located on 18q11.2, encodes a protein involved in cell cycle regulation through interactions with several cyclin-dependent kinases	Atrazine	↑[31]	Promoter	↓[42]	Body
CDH1	Located on 16q22.1, encodes a classical cadherin of the cadherin superfamily	Imidacloprid	↓[39]	Promoter	↑[43]	Body
		Persistent organic pollutants	↑[40]	Promoter
PDX1	Located on 13q12.2, the protein encoded by this gene is a transcriptional activator of several genes, including insulin, somatostatin, glucokinase, islet amyloid polypeptide, and glucose transporter type 2	Fonofos, parathion, terbufos	↑[36]	Promoter	↑[45]	Intronic region
PTEN	Located on 10q23.31, the protein encoded by this gene is a phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase	Diazinon	↑[37]	Promoter	↓[46]	Promoter
PTPRN2	Located on 7q36.3, encodes a protein with sequence similarity to receptor-like protein tyrosine phosphatases	Pesticide	↓[38]	Body	↓	Body[47]/CpG island[48]

¹The methylation status and location of genes in pesticide exposure and DNA methylation.

²The methylation status and location of genes in DNA methylation and the onset of type 2 diabetes.

↑: Hypermethylation; ↓: Hypomethylation; T2D: Type 2 diabetes; CpG: Cytosine-phosphate-Guanine.