“Using whole-exome sequencing, we identified a single low-frequency variant in the MODY3-causing gene HNF1A that is associated with type 2 diabetes in Latino populations and may affect protein function,” Karol Estrada, PhD, of the Broad Institute of Harvard and MIT, and colleagues reported in the Journal of the American Medical Association.
Hispanic populations have one of the highest prevalences of type 2 diabetes worldwide, so identifying genetic factors associated with the disease could improve risk prediction and treatments.
To test one genetic variant for allele frequency and association with type 2 diabetes, the researchers sequenced DNA samples from 3,756 Mexican and United States Latino patients, defined as persons who trace their origin to Central and South America, and other Spanish cultures (n=1,794 for patients with type 2 diabetes; n=1,962 for patients without diabetes).
A single rare missense variant (c.1522G>A [p.E508K]) located in the HNF1A gene was associated with about a five times greater odds of type 2 diabetes, but it was not associated with an early-onset form of diabetes (odds ratio, 4.16; 95% CI: 1.75-9.92; P=0.0013).
This variant was observed only in Latino patients — 0.36 percent of participants without type 2 diabetes and 2.1 percent of participants with it. Carriers and noncarriers of the p.E508K mutation with type 2 diabetes did not differ in clinical characteristics, including age onset (mean age: 45.3 versus 47.5 years; P=0.49; mean BMI: 28.2 kg/m² versus 29.3 kg/m²; P=0.19).
“Further research is warranted to evaluate the clinical relevance of these findings, including the benefits of selective population screening and the choice of genotype-guided therapeutic regimens,” concluded the researchers.