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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±8.9μgL−1] than the subjects with wild (GM: 36.3±8.5μgL−1) and heterozygous (GM: 34.4±6.9μgL−1) genotypes. Miners with CYP2D6∗2 variant genotypes showed low prolactin levels (GM: 13.13±1.6ngmL−1) compared to the wild (GM: 16.4.4±1.5μgL−1) and heterozygous (GM: 18.7±1.6ngmL−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. [Copyright &y& Elsevier]

The article discusses the findings of a study conducted in Kolkata, India on the genetic aspects of glaucoma. It is said that primary open angle glaucoma (POAG) and primary congenital glaucoma (PCG) exhibit defects in the gene called myocilin, trabecular meshwork inducible glucocorticoid response (MYOC) and cytochrome P1B1 (CYP1B1), respectively. Elevated intraocular pressure (IOP) is the major risk factor of glaucoma. The phenotypic findings regarding a homozygous genetic variant for a 29-year old man diagnosed to have POAG is discussed.

Genotypes of the drug-metabolizing enzyme CYP2D6 influence plasma levels of 25% of commonly prescribed drugs. This is the first study in India to investigate the genotype-phenotype relationship of CYP2D6.~Background~Background~To study the influence of some CYP2D6 genotypes on the metabolism of its substrate dextromethorphan in healthy South Indian volunteers and to assess the contribution of the CYP2D6*10 and CYP2D6*4 alleles.~Aim~Objective~Twenty-six subjects from a previous CYP2D6 genotyping study of healthy volunteers were included for phenotyping in this study. Selected volunteers belonged to any one of three genotype groups:Group I - two normal activity alleles, Group II - one reduced activity allele and one normal activity allele and Group III - one loss of function allele along with either a wild type or reduced activity allele. Volunteers were phenotyped for the CYP2D6 enzyme using dextromethorphan as probe drug. Concentrations of the parent drug and metabolite dextrorphan were estimated using high performance liquid chromatography. Metabolic ratios were calculated as the ratio of parent drug to metabolite in 0-8h urine samples.~Materials and Methods~Methods~Metabolic ratios from each genotype group were compared using the Mann-Whitney test at 5% significance, to observe their difference between genotype groups.~Statistical Analysis~Methods~The mean metabolic ratios+/-SD in Groups I, II and III were 0.0039+/-0.0031, 0.0032+/-0.0017 and 0.0391+/-0.0331 respectively. The mean metabolic ratio of Group III was significantly higher when compared with Groups I or II. In heterozygous individuals, the *1 or *2 alleles compensated for the reduced enzyme activity due to the *10 allele. However, if a heterozygous individual had a *4 allele, the reduced enzyme activity could not be compensated by the *1 or *2 alleles.~Results~Results~The CYP2D6 enzyme activity was found to be decreased in individuals carrying *4 or *5 alleles. The *1 or *2 allele could compensate for the reduced function due to *10 allele, but not for the loss of function due to *4 allele.~Conclusions~Conclusions [ABSTRACT FROM AUTHOR]