rs1050828

rs1050828, also known as c.292G>A, p.Val98Met and V98M as well as the G6PD A- mutation, is a SNP residing in the G6PD gene and is located the X chromosome. G6PD codes for the enzyme glucose-6-phosphate dehydrogenase, which helps protect the cell from oxidative damage. Depending on genotype, an individual may possess one or two primary versions of the G6PD gene; type A and type B. Type A is predominantly found in people who have African ancestry. Mutations of G6PD can cause varying degrees of G6PD deficiency, which is a disease affecting red blood cells. For example, an G to A substitution mutation at the rs1050828 (also referred to as G202A) is associated with a reduction of G6PD. The G6PD deficient genotype A- (~8-20% reduction of G6PD) is typically defined by the possession of the rs1050828 A allele (rs1050828(A;A)). In addition, individuals who are type A- almost always possess the rs1050829 G allele. G6PD deficiency frequency is highest in malarial regions where G6PD deficient individuals are typically less affected by malarial infection (). Also, the literature suggests that there is association between the rs1050828 locus and various red blood cell traits in African Americans. A 2019 publication reports that this variant also has the effect of lowering HbA1c values by ~0.88%-units in hemizygous men and 0.34%-units in heterozygous women. The authors suggest that when using Hb1Ac values to diagnose type-2 diabetes, those units should be added to the measured Hb1Ac level, and a diagnosis should then be made if the sum is >6.5% (the standard diagnostic threshold). A total of 72 SNPs were genotyped in two populations in eastern Sudan (Hausa and Massalit), as well as, a cohort of malaria hospital patients and a control sample set (n=449). The study found that in comparison to controls (n=69), Massalit individuals (n=60) who possess the rs105828 A allele were less susceptible to malarial infection (P=0.04). Study surveyed 49,094 SNPs (covering ~2,100 candidate genes)in Caucasian (n=23,439) and African American (n=7,112) individuals from five different population cohorts. Genome wide association results include that rs1050828 A allele found in African American individuals is strongly associated with certain erythrocyte phenotypes including; lower red blood cell, hemoglobin and hematocrit counts (all p values -13 ). In order to identify SNPs associated with different red blood cell phenotypic traits a genome-wide association study was conducted on African Americans (n=16,500). The SNP rs1050828 was found to be associated with hemoglobin (Hgb), hematocrit (Hct), mean corpuscular volume (MCV), and RBC count. A cohort of African American medical patients (n=1904) was analyzed in a genome-wide association study where loci were correlated with certain red blood cell traits. The rs1050828 locus is associated with RBC count (P=4x10 -13 ), mean corpuscular volume (P=1x10 -14 ), and mean corpuscular hemoglobin (P=9x10 -9 ).

-;C

The rs1050828 G allele is located within the G6PD gene and is associated with 'normal' levels of glucose-6-phosphate dehydrogenase enzyme production.

T;T

The A allele is associated with a reduction in glucose-6-phosphate dehydrogenase (G6PD) and is a diagnostic SNP of the type A- G6PD deficiency genotype. Type A- is predominantly found in individuals with African ancestry. The rs1050828 A allele is also associated with malarial resistance. Because rs1050828 is located on the X chromosome, males are either hemizygous for the normal G allele or this deficiency allele.

C;T

The rs1050828 A allele is a diagnostic SNP of the type A- G6PD deficiency genotype. While the G allele (rs1050828(G;G)) is associated with 'normal' levels of glucose-6-phosphate dehydrogenase, the A allele is associated with a reduction of G6PD production. Because rs1050828 is located on the X chromosome, only females can be heterozygous for both the A and G allele. Furthermore, due to the process of X chromosome lyonization, the severity of G6PD deficiency will vary across females. G6PD type A- is predominantly found in individuals with African ancestry while the G allele is found in other ethnic groups. The rs1050828 A allele is also associated with malarial resistance.

C;C

The rs1050828 G allele is located within the G6PD gene and is associated with 'normal' levels of glucose-6-phosphate dehydrogenase enzyme production.