A genetic variation common in people of African ancestry is associated with an increased risk of complications from diabetes, including diabetic retinopathy, according to a new study.
The study, in Nature Medicine,1 found that the diagnosis of diabetes may be delayed in people who carry the variant, G6PDdef, because it is associated with reduced levels of HbA1c, a widely used clinical marker of blood glucose levels.
This, in turn, could delay treatment, leading to increased risked of complications, including increased risk of diabetic eye disease.
It is estimated that more than 400 million people worldwide have G6PD deficiency. Common only in African and in some Asian populations, this genetic variation may have evolved as a protection against severe malaria.
Ethnic Diversity
Diabetic retinopathy, damage to retinal blood vessels and nerves at the back of the eye that can cause permanent vision loss, have previously been linked to genetic variations called single nucleotide polymorphisms, or SNPs, but these associations have been studied primarily in individuals of European and Asian ancestry.
This new multi-institutional study was led by Vanderbilt University Medical Center (VUMC). It was the largest ancestry-stratified, SNP-based estimation of the heritability of diabetic retinopathy conducted to date. It included an unprecedented number of individuals of non-Hispanic African ancestry – more than 46,000.
Using the New Knowledge
The researchers concluded that testing for genetic variations that cause G6PD deficiency could lead to improvements in the way clinicians diagnose and treat diabetes, thereby helping to reduce the long-observed disparity in diabetes complications between individuals of European and African ancestries, the paper concluded.
“This discovery could lead to changes in the way diabetes is managed for millions of patients,” said Associate Professor Dr Todd Edwards, from VUMC.2
“More needs to be done… to establish the best way to use this knowledge to prevent diabetes complications,” said Assoc Prof Edwards. “Now that process can begin.”
“While this discovery may impact how millions of individuals manage their diabetes, it also highlights the importance of including diverse populations in biomedical research,” said the paper’s first author, Dr Joseph Breeyear, a postdoctoral research fellow at the National Institute of Environmental Health Sciences of the National Institutes of Health (NIH).
“By including underrepresented individuals, we can identify genetic variations that affect health outcomes,” he said.
The current study detected nine previously unreported loci, or positions on the chromosomes, which were associated with diabetic retinopathy, including an evolutionarily adaptive genetic variant that potentially may explain some of the racial disparity in diabetes complications.
The G6PDdef variant results in deficiency of the enzyme glucose 6-phosphate dehydrogenase.
It is associated with a shorter red blood cell lifespan, which lowers HbA1c levels but not blood glucose levels. This “mismatch” can mask the true extent of hyperglycaemia: in individuals who carry the G6PDdef mutation, HbA1c levels systematically underestimate blood glucose levels.
“With comprehensive screening… and subsequent standard-of-care treatment, possibly aimed at glucose rather than HbA1c targets, nearly 12% of diabetic retinopathy cases and 9% of diabetic neuropathy cases in individuals of non-Hispanic African ancestry could be avoided in the US alone,” the researchers concluded.
References
- Breeyear, J.H., Hellwege, J.N., Edwards, T.L., et al. Adaptive selection at G6PD and disparities in diabetes complications. Nat Med. Published June 25, 2024. DOI: 10.1038/s41591-024-03089-1.
- Vanderbilt University Medical Center, Gene variant may underlie diabetes disparities: Study (media release), 25 June 2024, available at: eurekalert.org/news-releases/1049282 [accessed June 2024].
