A polymorphism in PTPN2 gene is associated with an earlier onset of type 1 diabetes.
The Wellcome Trust Case Control Consortium (WTCCC) genome-wide study found association of PTPN2 with three autoimmune diseases, among them is type 1 diabetes (T1D). This result was confirmed by a follow-up study that pointed to new independent signals within the region. However, both studies were performed in patients with an early-onset T1D. We aimed at replicating the previous results and studying the influence of these polymorphisms in the age at T1D debut. We genotyped 439 T1D Spanish subjects (age at onset, 1 to 65 years) and 861 controls for two PTPN2 single nucleotide polymorphisms (SNPs), rs2542151 and rs478582, and studied the effect of both polymorphisms in age at onset through stratified and continuous analyses. The frequency of rs2542151*G carriers was significantly higher in the early-onset group compared with late-onset patients (p = 0.023) and with controls (OR = 1.61 [1.14-2.26]; p = 0.005). No significant differences were found between controls and late-onset patients. The log-rank chi-square test for the Kaplan-Meier plots (carriers of susceptibility allele vs non carriers) was statistically significant (χ (1df) (2)  = 4.485; p = 0.034), yielding an earlier disease debut for G carriers. The analysis of the SNP rs478582 did not reach statistical significance. In summary, we replicate the association detected by the WTCCC and propose that the rs2542151*G allele confers risk to an earlier onset of T1D.
Immunology Department, Hospital Clínico San Carlos, Martín Lagos s/n, 28040, Madrid, Spain. lauraep80@yahoo.es
Laura
L
Espino-Paisan
Hermenegildo
H
de la Calle
Miguel
M
Fernández-Arquero
Maria Angeles
MA
Figueredo
Emilio G
EG
de la Concha
Elena
E
Urcelay
Jose Luis
JL
Santiago
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2 / Q000235:genetics*; D013030:Spain; D044465:White People / Q000235:genetics; D055815:Young Adult
C516649:PTPN2 protein, human; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2
Immunol Rev. 2009 Mar;228(1):325-41
19290937
Scand J Immunol. 1998 Jan;47(1):48-53
9467658
Gastroenterology. 2009 Dec;137(6):2030-2040.e5
19818778
Nature. 2007 Jun 7;447(7145):661-78
17554300
Diabetes. 1996 Feb;45(2):178-82
8549862
Diabetologia. 2008 Sep;51(9):1653-8
18563381
Nat Genet. 2007 Jul;39(7):857-64
17554260
Immunogenetics. 2010 Feb;62(2):101-7
20033399
N Engl J Med. 2008 Dec 25;359(26):2767-77
19073967
Diabetes. 2009 Jun;58(6):1283-91
19336676