Association of calpain-10 polymorphisms with type 2 diabetes in the Tunisian population.
BACKGROUND
Genome-wide analyses of the genetic predisposition to type 2 diabetes mellitus (T2DM) in different isolates and populations have identified regions of interest called non insulin-dependent diabetes mellitus (NIDDM) 1, 2, 3 and 4. At the NIDDM1 locus (2q37.3), calpain-10 (CAPN10) encodes for a ubiquitously expressed protease implicated in the two fundamental pathophysiological aspects of T2DM. This is a report of the results of a study of the association of four CAPN10 polymorphisms with T2DM in the Tunisian population.


METHODS
A total of 222 T2DM patients with a diabetes duration of 10 years or more and 206 healthy controls were enrolled to analyze the frequency distribution of four CAPN10 polymorphisms (UCSNP-43, UCSNP-19, UCSNP-110 and UCSNP-63) using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in the Tunisian population. We also investigated the association of T2DM with different haplotypes and haplotype combinations.


RESULTS
Only the A allele of UCSNP-43 showed an association with T2DM (odds ratio, OR=1.86). We also identified a novel combination of haplotypes (121/221) defined by three polymorphisms (UCNSP-43, -19 and -63) that is associated with an increased risk of T2DM (OR=2.38).


CONCLUSIONS
In this study involving the Tunisian population, we identified genetic variants within CAPN10 that are linked with T2DM and a novel haplotype combination, 121/221, associated with an increased susceptibility to T2DM.
Kifagi
C
C
Targets for Diagnosis and Therapeutic in the Human Pathology Research Unit, Center of Biotechnology of Sfax and Laboratoire International Associé No 135, Sfax, Tunisia.
Makni
K
K
Mnif
F
F
Boudawara
M
M
Hamza
N
N
Rekik
N
N
Abid
M
M
Rebaï
A
A
Granier
C
C
Jarraya
F
F
Ayadi
H
H
D000368:Aged; D002154:Calpain / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012016:Reference Values; D014416:Tunisia
D002154:Calpain; C415197:calpain 10