Mouse Cyb5r3 ( NADH-cytochrome b5 reductase 3) ELISA Kit

Cytochrome b (5) (encoded by CYB5A) and NADH cytochrome b (5) reductase (encoded by CYB5R3) detoxify aromatic and heterocyclic amine mammary carcinogens found in cigarette smoke. We hypothesized that CYB5A and CYB5R3 polymorphisms would be associated with breast cancer risk in women. We characterized the prevalence of 18 CYB5A and CYB5R3 variants in genomic DNA from African American (AfrAm) and Caucasian (Cauc) women from the Carolina Breast Cancer Study population (1,946 cases and 1,747 controls) and determined their associations with breast cancer risk, with effect modification by smoking. A CYB5R3 variant, I1M+6T (rs8190370), was significantly more common in breast cancer cases (MAF 0.0238) compared with controls (0.0169, p = 0.039); this was attributable to a higher MAF in AfrAm cases (0.0611) compared with AfrAm controls (0.0441, p = 0.046; adjusted OR 1.41, CI 0.98-2.04; p = 0.062). When smoking was considered, I1M+6T was more strongly associated with breast cancer risk in AfrAm smokers (adjusted OR 2.10, 1.08-4.07; p = 0.028) compared with never smokers (OR = 1.21; 0.77-1.88; p for interaction = 0.176). I1M+6T and three additional CYB5R3 variants, -251T, I8-1676C, and *392C, as well as two CYB5A variants, 13G and I2-992T, were significantly more common in AfrAms compared with Caucs. CYB5R3 I1M+6C > T should be considered in future molecular epidemiologic studies of breast cancer risk in AfrAms. Further, variants in CYB5A and CYB5R3 should be considered in the evaluation of other tumors in AfrAms that are associated with aromatic and heterocyclic amine exposures, to include prostate, bladder, and colon cancers.

Genetic modifiers of anemia inPlasmodium falciparuminfection and sickle cell disease (SCD) are not fully known. Both conditions are associated with oxidative stress, hemolysis and anemia. TheCYB5R3gene encodes cytochrome b5 reductase 3, which converts methemoglobin to hemoglobin through oxidation of NADH.CYB5R3(c.350C > G)encoding CYB5R3(T117S), the most frequent recognized African-specific polymorphism, does not have known functional significance, but its high allele frequency (23% in African Americans) suggests a selection advantage. Glucose-6-phosphate dehydrogenase (G6PD) is essential for protection from oxidants; its African-polymorphic X-linked A+ and A- alleles, and other variants with reduced activity, coincide with endemic malaria distribution, suggesting protection from lethal infection. We examined the association ofCYB5R3(c.350C > G)with severe anemia (hemoglobin <5 g/dL) in the context ofG6PDA+ and A- status among 165 Zambian children with malaria.CYB5R3(c.350C > G)offered protection against severe malarial anemia in children without G6PD deficiency (G6PDwild type or A+/A- heterozygotes) (odds ratio 0.29,P= .022) but not inG6PDA+ or A- hemizygotes/homozygotes. We also examined the relationship ofCYB5R3(c.350C > G)with hemoglobin concentration among 267 children and 321 adults and adolescents with SCD in the US and UK and found higher hemoglobin in SCD patients without G6PD deficiency (beta = 0.29,P= .022 children; beta = 0.33,P= .004 adults). Functional studies in SCD erythrocytes revealed mildly lower activity of native CYB5R3(T117S)compared to wildtype CYB5R3 and higher NADH/NAD+ ratios. In conclusion,CYB5R3(c.350C > G)appears to ameliorate anemia severity in malaria and SCD patients without G6PD deficiency, possibly accounting forCYB5R3(c.350C > G)selection and its high prevalence.