Association of G6PD variants with hemoglobin A1c and impact on diabetes diagnosis in East Asian individuals.
BMJ Open Diabetes Res Care
; 8(1)2020 03.
Article
en En
| MEDLINE
| ID: mdl-32209585
ABSTRACT
OBJECTIVE:
Hemoglobin A1c (HbA1c) accuracy is important for diabetes diagnosis and estimation of overall glycemia. The G6PD-Asahi variant which causes glucose-6-phosphate dehydrogenase (G6PD) deficiency has been shown to lower HbA1c independently of glycemia in African ancestry populations. As different G6PD variants occur in Asian ancestry, we sought to identify Asian-specific G6PD variants associated with HbA1c. RESEARCH DESIGN ANDMETHODS:
In eight Asian population-based cohorts, we performed imputation on the X chromosome using the 1000 Genomes reference panel and tested for association with HbA1c (10 005 East Asians and 2051 South Asians). Results were meta-analyzed across studies. We compared the proportion of individuals classified as having diabetes/pre-diabetes by fasting glucose ≥100 mg/dL or HbA1c ≥5.7% units among carriers and non-carriers of HbA1c-associated variants.RESULTS:
The strongest association was a missense variant (G6PD-Canton, rs72554665, minor allele frequency=2.2%, effect in men=-0.76% unit, 95% CI -0.88 to -0.64, p=1.25×10-27, n=2844). Conditional analyses identified a secondary distinct signal, missense variant (G6PD-Kaiping, rs72554664, minor allele frequency=1.6%, effect in men=-1.12 % unit, 95% CI -1.32 to -0.92, p=3.12×10-15, pconditional_Canton=7.57×10-11). Adjusting for glucose did not attenuate their effects. The proportion of individuals with fasting glucose ≥100 mg/dL did not differ by carrier status of G6PD-Canton (p=0.21). Whereas the proportion of individuals with HbA1c ≥5.7% units was lower in carriers (5%) compared with non-carriers of G6PD-Canton (30%, p=0.03).CONCLUSIONS:
We identified two G6PD variants in East Asian men associated with non-glycemic lowering of HbA1c. Carriers of these variants are more likely to be underdiagnosed for diabetes or pre-diabetes than non-carriers if screened by HbA1c without confirmation by direct glucose measurements.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Diabetes Mellitus
/
Glucosafosfato Deshidrogenasa
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Humans
/
Male
Idioma:
En
Revista:
BMJ Open Diabetes Res Care
Año:
2020
Tipo del documento:
Article