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Title: Association of G6PD variants with hemoglobin A1c and impact on diabetes diagnosis in East Asian individuals
Authors: Leong, A.
Lim, V.J.Y. 
Wang, C.
Chai, J.-F. 
Dorajoo, R.
Heng, C.-K. 
Van Dam, R.M. 
Koh, W.-P. 
Yuan, J.-M.
Jonas, J.B.
Wang, Y.X.
Wei, W.-B.
Liu, J. 
Reilly, D.F.
Wong, T.-Y. 
Cheng, C.-Y. 
Sim, X. 
Keywords: A1C
diagnostic criteria
genetic association
Issue Date: Mar-2020
Publisher: BMJ Publishing Group
Citation: Leong, A., Lim, V.J.Y., Wang, C., Chai, J.-F., Dorajoo, R., Heng, C.-K., Van Dam, R.M., Koh, W.-P., Yuan, J.-M., Jonas, J.B., Wang, Y.X., Wei, W.-B., Liu, J., Reilly, D.F., Wong, T.-Y., Cheng, C.-Y., Sim, X. (2020-03). Association of G6PD variants with hemoglobin A1c and impact on diabetes diagnosis in East Asian individuals. BMJ Open Diabetes Research and Care 8 (1) : e001091. ScholarBank@NUS Repository.
Rights: Attribution-NonCommercial 4.0 International
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 and methods 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, p conditional_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. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Source Title: BMJ Open Diabetes Research and Care
ISSN: 20524897
DOI: 10.1136/bmjdrc-2019-001091
Rights: Attribution-NonCommercial 4.0 International
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