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@article{Bonnefond:2009:10.2337/db09-0652,
author = {Bonnefond, A and Vaxillaire, M and Labrune, Y and Lecoeur, C and Chevre, J-C and Bouatia-Naji, N and Cauchi, S and Balkau, B and Marre, M and Tichet, J and Riveline, J-P and Hadjadj, S and Gallois, Y and Czernichow, S and Hercberg, S and Kaakinen, M and Wiesner, S and Charpentier, G and Levy-Marchal, C and Elliott, P and Jarvelin, M-R and Horber, F and Dina, C and Pedersen, O and Sladek, R and Meyre, D and Froguel, P},
doi = {10.2337/db09-0652},
journal = {Diabetes},
pages = {2687--2697},
title = {Genetic variant m HK1 is associated with a proanemic state and A1C but not other glycemic control-related traits},
url = {http://dx.doi.org/10.2337/db09-0652},
volume = {58},
year = {2009}
}

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TY  - JOUR
AB  - OBJECTIVE A1C is widely considered the gold standard for monitoring effective blood glucose levels. Recently, a genome-wide association study reported an association between A1C and rs7072268 within HK1 (encoding hexokinase 1), which catalyzes the first step of glycolysis. HK1 deficiency in erythrocytes (red blood cells [RBCs]) causes severe nonspherocytic hemolytic anemia in both humans and mice.RESEARCH DESIGN AND METHODS The contribution of rs7072268 to A1C and the RBC-related traits was assessed in 6,953 nondiabetic European participants. We additionally analyzed the association with hematologic traits in 5,229 nondiabetic European individuals (in whom A1C was not measured) and 1,924 diabetic patients. Glucose control–related markers other than A1C were analyzed in 18,694 nondiabetic European individuals. A type 2 diabetes case-control study included 7,447 French diabetic patients.RESULTS Our study confirms a strong association between the rs7072268–T allele and increased A1C (β = 0.029%; P = 2.22 × 10−7). Surprisingly, despite adequate study power, rs7072268 showed no association with any other markers of glucose control (fasting- and 2-h post-OGTT–related parameters, n = 18,694). In contrast, rs7072268–T allele decreases hemoglobin levels (n = 13,416; β = −0.054 g/dl; P = 3.74 × 10−6) and hematocrit (n = 11,492; β = −0.13%; P = 2.26 × 10−4), suggesting a proanemic effect. The T allele also increases risk for anemia (836 cases; odds ratio 1.13; P = 0.018).CONCLUSIONS HK1 variation, although strongly associated with A1C, does not seem to be involved in blood glucose control. Since HK1 rs7072268 is associated with reduced hemoglobin levels and favors anemia, we propose that HK1 may influence A1C levels through its anemic effect or its effect on glucose metabolism in RBCs. These findings may have implications for type 2 diabetes diagnosis and clinical management because anemia i
AU  - Bonnefond,A
AU  - Vaxillaire,M
AU  - Labrune,Y
AU  - Lecoeur,C
AU  - Chevre,J-C
AU  - Bouatia-Naji,N
AU  - Cauchi,S
AU  - Balkau,B
AU  - Marre,M
AU  - Tichet,J
AU  - Riveline,J-P
AU  - Hadjadj,S
AU  - Gallois,Y
AU  - Czernichow,S
AU  - Hercberg,S
AU  - Kaakinen,M
AU  - Wiesner,S
AU  - Charpentier,G
AU  - Levy-Marchal,C
AU  - Elliott,P
AU  - Jarvelin,M-R
AU  - Horber,F
AU  - Dina,C
AU  - Pedersen,O
AU  - Sladek,R
AU  - Meyre,D
AU  - Froguel,P
DO  - 10.2337/db09-0652
EP  - 2697
PY  - 2009///
SN  - 0012-1797
SP  - 2687
TI  - Genetic variant m HK1 is associated with a proanemic state and A1C but not other glycemic control-related traits
T2  - Diabetes
UR  - http://dx.doi.org/10.2337/db09-0652
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000271490900031&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://diabetes.diabetesjournals.org/content/58/11/2687
UR  - http://hdl.handle.net/10044/1/85669
VL  - 58
ER  -

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