title: Genetic polymorphism of CYP2D6∗2 C→T 2850, GSTM1, NQO1 genes and their correlation with biomarkers in manganese miners of Central India.
abstract: Manganese (Mn) intoxication is most often regarded as an occupational manifestation and occurs in places such as manganese mines, dry cell battery plants and ceramic industries. In the present study, the influence of genetic polymorphism in cytochrome P450 2D6 (CYP2D6∗2), glutathione S-transferase M1 (GSTM1) and NAD(P)H quinone oxidoreductase 1 (NQO1) genes on blood manganese and plasma prolactin concentrations in manganese miners was investigated. Genotyping of CYP2D6∗2 C→T 2850 and NQO1 C→T 609 was carried out using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) whereas the genotyping of GSTM1 was carried out by multiplex PCR using beta globin as an internal control. Manganese miners with CYP2D6∗2 C→T 2850 variant genotype had relatively low Mn concentration [GM: 21.4±8.9 μg L(-1)] than the subjects with wild (GM: 36.3±8.5 μg L(-1)) and heterozygous (GM: 34.4±6.9 μg L(-1)) genotypes. Miners with CYP2D6∗2 variant genotypes showed low prolactin levels (GM: 13.13±1.6 ng mL(-1)) compared to the wild (GM: 16.4.4±1.5 μg L(-1)) and heterozygous (GM: 18.7±1.6 ng mL(-1)) genotypes. Gene-gene interaction studies also revealed that the subjects with CYP2D6∗2 C→T 2850 variant genotypes had low levels of Mn and prolactin. Our new findings suggest that CYP2D6∗2 C→T 2850 variant genotypes can regulate plasma prolactin levels in manganese miners of Central India and could be involved in the fast metabolism of blood manganese, compared to wild and heterozygous genotypes.
authors.affiliation: Environmental Health Division, National Environmental Engineering Research Institute (NEERI), Nagpur, India.
authors.forename: Nadimuthu
authors.initials: N
authors.lastname: Vinayagamoorthy
authors.forename: Kannan
authors.initials: K
authors.lastname: Krishnamurthi
authors.forename: Sivanesan Saravana
authors.initials: SS
authors.lastname: Devi
authors.forename: Pravin K
authors.initials: PK
authors.lastname: Naoghare
authors.forename: Raka
authors.initials: R
authors.lastname: Biswas
authors.forename: Arup R
authors.initials: AR
authors.lastname: Biswas
authors.forename: Sreemanta
authors.initials: S
authors.lastname: Pramanik
authors.forename: Ashok R
authors.initials: AR
authors.lastname: Shende
authors.forename: Tapan
authors.initials: T
authors.lastname: Chakrabarti
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007194:India; D008297:Male; D008345:Manganese / Q000097:blood*; D020149:Manganese Poisoning / Q000097:blood / Q000235:genetics; D008875:Middle Aged; D008906:Mining; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics*; D016273:Occupational Exposure / Q000032:analysis; D020641:Polymorphism, Single Nucleotide; D011388:Prolactin / Q000097:blood
chemical_list: D015415:Biomarkers; D019389:Cytochrome P-450 CYP2D6; D005982:Glutathione Transferase; D008345:Manganese; D016660:NAD(P)H Dehydrogenase (Quinone); D011388:Prolactin; C447479:NQO1 protein, human