Comprehensive screening for reg1alpha gene rules out association with tropical calcific pancreatitis.
OBJECTIVE
To investigate the allelic and haplotypic association of reg1alpha gene with tropical calcific pancreatitis (TCP). Since TCP is known to have a variable genetic basis, we investigated the interaction between mutations in the susceptibility genes, SPINK1 and CTSB with reg1alpha polymorphisms.


METHODS
We analyzed the polymorphisms in the reg1alpha gene by sequencing the gene including its promoter region in 195 TCP patients and 150 ethnically matched controls, compared their allele and haplotype frequencies, and their association with the pathogenesis and pancreaticolithiasis in TCP and fibro-calculous pancreatic diabetes.


RESULTS
We found 8 reported and 2 novel polymo-rphisms including an insertion-deletion polymorphism in the promoter region of reg1alpha. None of the 5'UTR variants altered any known transcription factor binding sites, neither did any show a statistically significant association with TCP. No association with any reg1alpha variants was observed on dichotomization of patients based on their N34S SPINK1 or L26V CTSB status.


CONCLUSIONS
Polymorphisms in reg1alpha gene, including the regulatory variants singly or in combination with the known mutations in SPINK1 and/or CTSB genes, are not associated with tropical calcific pancreatitis.
Mahurkar
Swapna
S
Genome Research Group, Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500007, India.
Bhaskar
Seema
S
Reddy
D Nageshwar
DN
Rao
G Venkat
GV
Chandak
Giriraj Ratan
GR
D002114:Calcinosis; D002352:Carrier Proteins / Q000235:genetics; D016022:Case-Control Studies; D002401:Cathepsin B / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005820:Genetic Testing; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D051847:Lithostathine / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics; D010179:Pancreas / Q000473:pathology; D010195:Pancreatitis / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D014330:Tropical Medicine; D014359:Trypsin Inhibitor, Kazal Pancreatic
D002352:Carrier Proteins; D051847:Lithostathine; C497617:REG1A protein, human; C486642:SPINK1 protein, human; D014359:Trypsin Inhibitor, Kazal Pancreatic; D002401:Cathepsin B