Genetic polymorphism of CYP2D6*2 C? T 2850, GSTM1, NQO1 genes and their correlation with biomarkers in manganese miners of Central India

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 lg L1 ] than the subjects with wild (GM: 36.3 ± 8.5 lg L1 ) and heterozygous (GM: 34.4 ± 6.9 lg L1 ) genotypes. Miners with CYP2D6*2 variant genotypes showed low prolactin levels (GM: 13.13 ± 1.6 ng mL1 ) compared to the wild (GM: 16.4.4 ± 1.5 lg L1 ) and heterozygous (GM: 18.7 ± 1.6 ng mL1 ) 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. 20

Sex Differences in Atrial Fibrillation Risk: The VITAL Rhythm Study.

Importance Women have a lower incidence of atrial fibrillation (AF) compared with men in several studies, but it is unclear whether this sex difference is independent of sex differences in prevalent cardiovascular disease (CVD), body size, and other risk factors. Objective To examine sex differences in AF incidence and whether AF risk factors differ by sex in a contemporary cohort of men and women without prevalent CVD. Design, Setting, and Participants This was a prospective cohort analysis within the Vitamin D and Omega-3 Trial (VITAL) Rhythm Study, a randomized trial that examined the effect of vitamin D and ω-3 fatty acid supplementation on incident AF among men 50 years or older and women 55 years or older without a prior history of prevalent AF, CVD, or cancer at baseline. Data were analyzed from September 29, 2020, to June 29, 2021. Exposures Sex, height, weight, body mass index (BMI), body surface area (BSA), and other AF risk factors at study enrollment. Main Outcomes and Measures Incident AF confirmed by medical record review. Results A total of 25 119 individuals (mean [SD] age, 67.0 [7.1] years; 12 757 women [51%]) were included in this study. Over a median (IQR) follow-up of 5.3 (5.1-5.7) years, 900 confirmed incident AF events occurred among 12 362 men (495 events, 4.0%) and 12 757 women (405 events, 3.2%). After adjustment for age and treatment assignment, women were at lower risk for incident AF than men (hazard ratio [HR], 0.68; 95% CI, 0.59-0.77; P < .001). The inverse association between female sex and AF persisted after adjustment for race and ethnicity, smoking, alcohol intake, hypertension, diabetes (type 1, type 2, gestational), thyroid disease, exercise, and BMI (HR, 0.73; 95% CI, 0.63-0.85; P <.001). However, female sex was positively associated with AF when height (HR, 1.39; 95% CI, 1.14-1.72; P = .001), height and weight (HR 1.49, 95% CI, 1.21-1.82; P <.001), or BSA (HR, 1.25; 95% CI, 1.06-1.49; P = .009) were substituted for BMI in the multivariate model. In stratified models, risk factor associations with incident AF were similar for women and men. Conclusions and Relevance In this cohort study, findings suggest that after controlling for height and/or body size, women without CVD at baseline were at higher risk for AF than men, suggesting that sex differences in body size account for much of the protective association between female sex and AF. These data underscore the importance of AF prevention in women