Determinants of HbA1c in nondiabetic Dutch adults: genetic loci and clinical and lifestyle parameters, and their interactions in the lifelines cohort study

被引：44

作者：

Jansen, H. ^{[1
]}

Stolk, R. P. ^{[1
]}

Nolte, I. M. ^{[1
]}

Kema, I. P. ^{[2
]}

Wolffenbuttel, B. H. R. ^{[3
]}

Snieder, H. ^{[1
]}

机构：

[1] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, NL-9700 RB Groningen, Netherlands

[2] Univ Groningen, Univ Med Ctr Groningen, Dept Lab Med, NL-9700 RB Groningen, Netherlands

[3] Univ Groningen, Univ Med Ctr Groningen, Dept Endocrinol, NL-9700 RB Groningen, Netherlands

来源：

JOURNAL OF INTERNAL MEDICINE | 2013年 / 273卷 / 03期

关键词：

genetic risk score; HbA1c; nondiabetic; replication; SNP; GENOME-WIDE ASSOCIATION; IRON-DEFICIENCY ANEMIA; GLYCATED HEMOGLOBIN; FASTING GLUCOSE; POPULATION; A(1C); RISK; ALCOHOL; HBA(1C); SMOKING;

D O I：

10.1111/joim.12010

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Jansen H, Stolk RP, Nolte IM, IP Kema, Wolffenbuttel BHR, Snieder H (University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands). Determinants of HbA1c in nondiabetic Dutch adults: genetic loci and clinical and lifestyle parameters, and their interactions in the LifeLines Cohort Study. J Intern Med 2013; 273: 283-293. Objectives Glycated haemoglobin (HbA1c) is associated with cardiovascular disease risk in individuals without diabetes, and its use has been recommended for diagnosing diabetes. Therefore, it is important to gain further understanding of the determinants of HbA1c. The aim of this study was to investigate the effects of genetic loci and clinical and lifestyle parameters, and their interactions, on HbA1c in nondiabetic adults. Design Population-based cohort study. Setting Three northern provinces of the Netherlands. Subjects A total of 2921 nondiabetic adults participating in the population-based LifeLines Cohort Study. Measurements Body mass index (BMI), waist circumference, HbA1c, fasting plasma glucose (FPG) and erythrocyte indices were measured. Data on current smoking and alcohol consumption were collected through questionnaires. Genome-wide genotyping was performed, and 12 previously identified single-nucleotide polymorphisms (SNPs) were selected for replication and categorized as glycaemic' and nonglycaemic' SNPs according to their presumed mechanism(s) of action on HbA1c. Genetic risk scores (GRSs) were calculated as the sum of the weighted effect of HbA1c-increasing alleles. Results Age, gender, BMI, FPG, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, current smoking and alcohol consumption were independent predictors of HbA1c, together explaining 26.2% of the variance in HbA1c, with FPG contributing 10.9%. We replicated three of the previously identified SNPs and the GRSs were also found to be independently associated with HbA1c. We found a smaller effect of the nonglycaemic GRS' in females compared with males and an attenuation of the effect of the GRS of all 12 SNPs with increasing BMI. Conclusions Our results suggest that a substantial portion of HbA1c is determined by nonglycaemic factors. This should be taken into account when considering the use of HbA1c as a diagnostic test for diabetes.

引用

页码：283 / 293

页数：11

共 43 条

[1]

Boeing H, 2000, AM J CLIN NUTR, V71, P1115

[2] Genetic Variant m HK1 Is Associated With a Proanemic State and A1C but Not Other Glycemic Control-Related Traits [J].

Bonnefond, Amelie ;

Vaxillaire, Martine ;

Labrune, Yann ;

Lecoeur, Cecile ;

Chevre, Jean-Claude ;

Bouatia-Naji, Nabila ;

Cauchi, Stephane ;

Balkau, Beverley ;

Marre, Michel ;

Tichet, Jean ;

Riveline, Jean-Pierre ;

Hadjadj, Samy ;

Gallois, Yves ;

Czernichow, Sebastien ;

Hercberg, Serge ;

Kaakinen, Marika ;

Wiesner, Susanne ;

Charpentier, Guillaume ;

Levy-Marchal, Claire ;

Elliott, Paul ;

Jarvelin, Marjo-Riitta ;

Horber, Fritz ;

Dina, Christian ;

Pedersen, Oluf ;

Sladek, Robert ;

Meyre, David ;

Froguel, Philippe .

DIABETES, 2009, 58 (11) :2687-2697

[3] A polymorphism within the G6PC2 gene is associated with fasting plasma glucose levels [J].

Bouatia-Naji, Nabila ;

Rocheleau, Ghislain ;

Van Lommel, Leentje ;

Lemaire, Katleen ;

Schuit, Frans ;

Cavalcanti-Proenca, Christine ;

Marchand, Marion ;

Hartikainen, Anna-Liisa ;

Sovio, Ulla ;

De Graeve, Franck ;

Rung, Johan ;

Vaxillaire, Martine ;

Tichet, Jean ;

Marre, Michel ;

Balkau, Beverley ;

Weill, Jacques ;

Elliott, Paul ;

Jarvelin, Marjo-Riitta ;

Meyre, David ;

Polychronakos, Constantin ;

Dina, Christian ;

Sladek, Robert ;

Froguel, Philippe .

SCIENCE, 2008, 320 (5879) :1085-1088

[4] Tobacco smoke is a source of toxic reactive glycation products [J].

Cerami, C ;

Founds, H ;

Nicholl, I ;

Mitsuhashi, T ;

Giordano, D ;

Vanpatten, S ;

Lee, A ;

AlAbed, Y ;

Vlassara, H ;

Bucala, R ;

Cerami, A .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (25) :13915-13920

[5] Variations in the G6PC2/ABCB11 genomic region are associated with fasting glucose levels [J].

Chen, Wei-Min ;

Erdos, Michael R. ;

Jackson, Anne U. ;

Saxena, Richa ;

Sanna, Serena ;

Silver, Kristi D. ;

Timpson, Nicholas J. ;

Hansen, Torben ;

Orru, Marco ;

Piras, Maria Grazia ;

Bonnycastle, Lori L. ;

Willer, Cristen J. ;

Lyssenko, Valeriya ;

Shen, Haiqing ;

Kuusisto, Johanna ;

Ebrahim, Shah ;

Sestu, Natascia ;

Duren, William L. ;

Spada, Maria Cristina ;

Stringham, Heather M. ;

Scott, Laura J. ;

Olla, Nazario ;

Swift, Amy J. ;

Najjar, Samer ;

Mitchell, Braxton D. ;

Lawlor, Debbie A. ;

Smith, George Davey ;

Ben-Shlomo, Yoav ;

Andersen, Gitte ;

Borch-Johnsen, Knut ;

Jorgensen, Torben ;

Saramies, Jouko ;

Valle, Timo T. ;

Buchanan, Thomas A. ;

Shuldiner, Alan R. ;

Lakatta, Edward ;

Bergman, Richard N. ;

Uda, Manuela ;

Tuomilehto, Jaakko ;

Pedersen, Oluf ;

Cao, Antonio ;

Groop, Leif ;

Mohlke, Karen L. ;

Laakso, Markku ;

Schlessinger, David ;

Collins, Francis S. ;

Altshuler, David ;

Abecasis, Goncalo R. ;

Boehnke, Michael ;

Scuteri, Angelo .

JOURNAL OF CLINICAL INVESTIGATION, 2008, 118 (07) :2620-2628

[6] Red cell life span heterogeneity in hematologically normal people is sufficient to alter HbA1c [J].

Cohen, Robert M. ;

Franco, Robert S. ;

Khera, Paramjit K. ;

Smith, Eric P. ;

Lindsell, Christopher J. ;

Ciraolo, Peter J. ;

Palascak, Mary B. ;

Joiner, Clinton H. .

BLOOD, 2008, 112 (10) :4284-4291

[7] New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk [J].

Dupuis, Josee ;

Langenberg, Claudia ;

Prokopenko, Inga ;

Saxena, Richa ;

Soranzo, Nicole ;

Jackson, Anne U. ;

Wheeler, Eleanor ;

Glazer, Nicole L. ;

Bouatia-Naji, Nabila ;

Gloyn, Anna L. ;

Lindgren, Cecilia M. ;

Magi, Reedik ;

Morris, Andrew P. ;

Randall, Joshua ;

Johnson, Toby ;

Elliott, Paul ;

Rybin, Denis ;

Thorleifsson, Gudmar ;

Steinthorsdottir, Valgerdur ;

Henneman, Peter ;

Grallert, Harald ;

Dehghan, Abbas ;

Hottenga, Jouke Jan ;

Franklin, Christopher S. ;

Navarro, Pau ;

Song, Kijoung ;

Goel, Anuj ;

Perry, John R. B. ;

Egan, Josephine M. ;

Lajunen, Taina ;

Grarup, Niels ;

Sparso, Thomas ;

Doney, Alex ;

Voight, Benjamin F. ;

Stringham, Heather M. ;

Li, Man ;

Kanoni, Stavroula ;

Shrader, Peter ;

Cavalcanti-Proenca, Christine ;

Kumari, Meena ;

Qi, Lu ;

Timpson, Nicholas J. ;

Gieger, Christian ;

Zabena, Carina ;

Rocheleau, Ghislain ;

Ingelsson, Erik ;

An, Ping ;

O'Connell, Jeffrey ;

Luan, Jian'an ;

Elliott, Amanda .

NATURE GENETICS, 2010, 42 (02) :105-U32

[8] The effect of iron deficiency anaemia on the levels of haemoglobin subtypes: possible consequences for clinical diagnosis [J].

El-Agouza, I ;

Abu Shahla, A ;

Sirdah, M .

CLINICAL AND LABORATORY HAEMATOLOGY, 2002, 24 (05) :285-289

[9] LIGHT-TO-MODERATE ALCOHOL INTAKE IS ASSOCIATED WITH ENHANCED INSULIN SENSITIVITY [J].

FACCHINI, F ;

CHEN, YDI ;

REAVEN, GM .

DIABETES CARE, 1994, 17 (02) :115-119

[10] A Genome-Wide Association Study of Treated A1C A Genetic Needle in an Environmental Haystack? [J].

Florez, Jose C. .

DIABETES, 2010, 59 (02) :332-334

← 1 2 3 4 5 →