ENPP1 K121Q polymorphism and obesity, hyperglycaemia and type 2 diabetes in the prospective DESIR Study.
OBJECTIVE
We assessed the predictive value of ectonucleotide pyrophosphatase/phosphodiesterase 1 gene (ENPP1) SNPs with regard to the risk of developing obesity and/or type 2 diabetes in a large French general population.


METHODS
We genotyped the ENPP1 SNPs K121Q (rs1044498), IVS20delT-11 (rs1799774) and A/G+1044TGA (rs7754561) in 5,153 middle-aged participants of the Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) cohort.


RESULTS
At baseline, the K121Q polymorphism was not associated either with BMI (p = 0.98) or with class I obesity (odds ratio [OR] 0.99, p = 0.81), but showed a borderline association with class II obesity (OR 1.65, p = 0.02). The K121Q variant was not associated with any trait during the 9-year follow-up. Pooled analyses both at baseline and at follow-up failed to show any association with hyperglycaemia (OR 1.08, p = 0.28) or type 2 diabetes (OR 1.15, p = 0.38). However, we did show an association of the Q121 allele with the risk of hyperglycaemia (OR 1.45, p = 0.001; n = 265) and type 2 diabetes (OR 1.65, p = 0.01; n = 103) in participants reporting a family history of type 2 diabetes. These results did not remain significant after a Bonferroni correction. The IVS20delT-11 and A/G+1044TGA polymorphisms and the three-allele risk haplotype (K121Q, IVS20delT-11 and A-->G+1044TGA [QdelTG]) were not associated with any trait, either at baseline or at follow-up.


CONCLUSIONS
In a general French population we did not find an association of the QdelTG risk haplotype with adult obesity and type 2 diabetes. We detected nominal evidence of association between the K121Q polymorphism and both severe adult obesity at baseline and the risk of hyperglycaemia or type 2 diabetes in participants with a family history of type 2 diabetes in pooled analyses both at baseline and follow-up.
Meyre
D
D
CNRS 8090-Institute of Biology, Pasteur Institute, Lille, France.
Bouatia-Naji
N
N
Vatin
V
V
Veslot
J
J
Samson
C
C
Tichet
J
J
Marre
M
M
Balkau
B
B
Froguel
P
P
D000328:Adult; D019943:Amino Acid Substitution; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D002874:Chromosome Mapping; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D006943:Hyperglycemia / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009765:Obesity / Q000150:complications / Q000235:genetics; D050177:Overweight / Q000235:genetics; D010727:Phosphoric Diester Hydrolases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011755:Pyrophosphatases / Q000235:genetics*
D001786:Blood Glucose; D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases
Am J Hum Genet. 2000 Nov;67(5):1174-85
11032783
Am J Hum Genet. 2002 Apr;70(4):920-34
11880950
Int J Obes (Lond). 2006 Feb;30(2):233-7
16231022
Diabetes. 2006 Nov;55(11):3175-9
17065358
Diabetes. 2007 Jan;56(1):256-64
17192490
Diabetes. 2006 Nov;55(11):3189-92
17065361
Am J Hum Genet. 2002 Nov;71(5):1044-50
12355400
J Mol Med (Berl). 2002 Dec;80(12):791-5
12483464
J Clin Endocrinol Metab. 2004 May;89(5):2044-7
15126519
Obes Res. 2003 May;11(5):603-5
12740448
Diabetes. 2000 Sep;49(9):1608-11
10969849
Diabetologia. 2006 Sep;49(9):2097-104
16865358
Nat Genet. 2005 Aug;37(8):863-7
16025115
Rev Epidemiol Sante Publique. 1996 Aug;44(4):373-5
8927780
Genet Med. 2002 Mar-Apr;4(2):45-61
11882781
J Clin Endocrinol Metab. 2006 Dec;91(12):4948-52
16968801
PLoS Med. 2005 Nov 1;2(12):e345
17570749
Science. 2005 Feb 18;307(5712):1072-9
15718463
JAMA. 2003 Jan 1;289(1):76-9
12503980
Diabetes. 2003 Feb;52(2):568-72
12540637
Metabolism. 2004 Apr;53(4):465-8
15045693
J Clin Endocrinol Metab. 2001 Dec;86(12):5888-91
11739459
Diabetes. 2004 May;53(5):1399-402
15111512
Horm Metab Res. 2006 Aug;38(8):524-9
16941279
Lancet. 2005 Oct 8;366(9493):1315-23
16214603
Stat Med. 2002 Jan 15;21(1):35-50
11782049
Diabetes Care. 1997 Jul;20(7):1183-97
9203460
Diabetes. 2000 Jan;49(1):13-9
10615944
Diabetes. 2006 Nov;55(11):3180-4
17065359
Diabetes. 2006 Sep;55(9):2626-30
16936213
Am J Hum Genet. 2001 May;68(5):1149-64
11283790
Am J Hum Genet. 2000 Jun;66(6):1871-81
10793009
Diabetes. 2001 Apr;50(4):831-6
11289049
J Hum Genet. 2006;51(6):559-66
16607460
Diabetes. 2005 Apr;54(4):1207-13
15793263
Diabetes. 2000 Sep;49(9):1601-3
10969847
Nature. 2007 Feb 22;445(7130):881-5
17293876
Nat Genet. 2000 Sep;26(1):76-80
10973253
Mol Genet Metab. 2006 Sep-Oct;89(1-2):174-84
16837224
Am J Hum Genet. 2003 Nov;73(5):1208-12
14574648
Diabetes. 2004 Mar;53(3):803-11
14988267
Diabetes Care. 2003 Feb;26(2):464-7
12547881
Diabetologia. 2004 May;47(5):871-7
15127203
Diabetes. 2005 Oct;54(10):3021-5
16186408
Diabetes. 1999 Sep;48(9):1881-4
10480624
Obesity (Silver Spring). 2007 Jan;15(1):1-4
17228024
Diabetes. 2004 Jan;53(1):228-34
14693720
Diabetes. 2006 Apr;55(4):1157-62
16567542
BMC Med Genet. 2005 Mar 22;6:11
15784141
Diabetes Obes Metab. 2006 Nov;8(6):703-8
17026496