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Polymorphisms in XPC and XPD genes modulate DNA damage in pesticide-exposed agricultural workers of Punjab, North-West India.
Molecular Biology Reports ( IF 2.8 ) Pub Date : 2020-06-19 , DOI: 10.1007/s11033-020-05600-6
Karashdeep Kaur 1, 2 , Rupinder Kaur 1
Affiliation  

The genetic susceptibility of individuals to the genotoxic effect of pesticides may be modulated by variations in genes involved in nucleotide excision repair (NER) pathway and therefore plays an important role in the evaluation of occupational risk. We aimed to evaluate the role of xeroderma pigmentosum complementation group C (XPC) Lys939Gln (A2920C, rs2228001), XPC Ala499Val (C2151T, rs2228000), xeroderma pigmentosum complementation group D (XPD) Asp312Asn (G23591A, rs1799793) and XPD Lys751Gln (A35931C, rs13181) in the modulation of DNA damage. A total of 450 subjects (225 pesticide-exposed agricultural workers and 225 age- and sex-matched controls) from Punjab, North-West India were recruited to study DNA damage by alkaline comet assay. Genotyping was carried out by PCR–RFLP using site-specific restriction enzymes. We found significant elevation in DNA damage parameters in pesticide-exposed agricultural workers as compared to the controls (p < 0.01). Association of comet tail length with XPC 939Gln/Gln (CC), XPD 312Asp/Asn (GA) and XPD 312Asn/Asn (AA) genotypes was observed. Frequency of cells showing DNA migration was significantly higher in exposed workers with variant XPC 939Gln/Gln (CC), XPD 312Asp/Asn (GA) and XPD 312Asn/Asn (AA) genotypes. Mean tail length was significantly increased in agricultural workers carrying XPD 312Asn/Asn (AA) genotype. Elevation in total comet DNA migration was also observed in exposed workers carrying variant XPC 939Lys/Gln (AC), XPC 939Gln/Gln (CC), XPC 499Val/Val (TT) and XPD 312Asn/Asn (AA) genotypes. Our results strongly indicate significant positive association of variant XPC and XPD genotypes with higher pesticide-induced DNA damage in North-West Indian agricultural workers.



中文翻译:

XPC和XPD基因的多态性可调节印度西北部旁遮普邦接触农药的农业工人的DNA损伤。

个体对农药的遗传毒性作用的遗传敏感性可通过核苷酸切除修复(NER)途径中涉及的基因变化来调节,因此在职业风险评估中起着重要作用。我们旨在评估干皮色素补充C组(XPC)Lys939Gln(A2920C,rs2228001),XPC Ala499Val(C2151T,rs2228000),干皮色素补充D组(XPD)Asp312Asn(G23591A,rs1799793)和XPD的作用Lys751Gln(A35931C,rs13181)在调节DNA损伤中。来自印度西北部旁遮普邦的共450名受试者(225名接触农药的农业工人以及225名年龄和性别匹配的对照)被招募来通过碱彗星试验研究DNA损伤。使用位点特异性限制酶通过PCR–RFLP进行基因分型。我们发现,与对照相比,接触农药的农业工人的DNA损伤参数显着升高(p <0.01)。观察到彗星尾巴长度与XPC 939Gln / Gln(CC),XPD 312Asp / Asn(GA)和XPD 312Asn / Asn(AA)基因型相关。XPC 939Gln / Gln(CC)和XPD变异的暴露工人中显示出DNA迁移的细胞频率明显更高312Asp / Asn(GA)和XPD 312Asn / Asn(AA)基因型。携带XPD 312Asn / Asn(AA)基因型的农业工人的平均尾巴长度显着增加。在携带变异XPC 939Lys / Gln(AC),XPC 939Gln / Gln(CC),XPC 499Val / Val(TT)和XPD 312Asn / Asn(AA)基因型的裸露工人中,总彗星DNA迁移也有所增加。我们的结果有力地表明,西北印度农业工人的XPCXPD基因型变异与较高的农药诱导的DNA损伤显着正相关。

更新日期:2020-06-22
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