SPINK1 is a susceptibility gene for fibrocalculous pancreatic diabetes in subjects from the Indian subcontinent.
Fibrocalculous pancreatic diabetes (FCPD) is a secondary cause of diabetes due to chronic pancreatitis. Since the N34S variant of the SPINK1 trypsin inhibitor gene has been found to partially account for genetic susceptibility to chronic pancreatitis, we used a family-based and case-control approach in two separate ethnic groups from the Indian subcontinent, to determine whether N34S was associated with susceptibility to FCPD. Clear excess transmission of SPINK1 N34S to the probands with FCPD in 69 Bangladeshi families was observed (P<.0001; 20 transmissions and 2 nontransmissions). In the total study group (Bangladeshi and southern Indian) the N34S variant was present in 33% of 180 subjects with FCPD, 4.4% of 861 nondiabetic subjects (odds ratio 10.8; P<.0001 compared with FCPD), 3.7% of 219 subjects with type 2 diabetes, and 10.6% of 354 subjects with early-onset diabetes (aged <30 years) (P=.02 compared with the ethnically matched control group). These results suggest that the N34S variant of SPINK1 is a susceptibility gene for FCPD in the Indian subcontinent, although, by itself, it is not sufficient to cause disease.
Hassan
Zahid
Z
Barts and the London Queen Mary's School of Medicine and Dentistry, London, United Kingdom.
Mohan
Viswananthan
V
Ali
Liaquat
L
Allotey
Rebecca
R
Barakat
Khalid
K
Faruque
M Omar
MO
Deepa
Raj
R
McDermott
Michael F
MF
Jackson
Alan E
AE
Cassell
Paul
P
Curtis
David
D
Gelding
Susan V
SV
Vijayaravaghan
Shanti
S
Gyr
Niklaus
N
Whitcomb
David C
DC
Khan
A K Azad
AK
Hitman
Graham A
GA
D002908:Chronic Disease; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007194:India; D008297:Male; D009154:Mutation; D010195:Pancreatitis / Q000150:complications / Q000235:genetics*; D010375:Pedigree; D014359:Trypsin Inhibitor, Kazal Pancreatic / Q000235:genetics* / Q000378:metabolism; D014361:Trypsin Inhibitors / Q000235:genetics / Q000378:metabolism
D014361:Trypsin Inhibitors; D014359:Trypsin Inhibitor, Kazal Pancreatic