title: The rs10993994 in the proximal MSMB promoter region is a functional polymorphism in Asian Indian subjects.
abstract: BACKGROUND
  The microseminoprotein gene encoding prostate secretory protein of 94 amino acids (PSP94) harbours a potential risk allele (rs10993994) for prostate cancer (PCa) in its promoter region. However, studies on rs10993994 have been sparse in Asian Indians.
  
  
  METHODS
  The present study recruited a sample population of 44 benign prostatic hyperplasia patients, 33 PCa patients and 60 healthy participants, of which, participants without other confounding risk factors for PCa were retained. The serum PSP94 (sPSP94) levels were measured by a serum-based ELISA in an earlier study. A novel RFLP technique was developed to screen for rs10993994 which was validated with direct sequencing.
  
  
  RESULTS
  Sequencing showed additional 4 SNPs (rs41274660, rs141211965, rs12770171, rs10669586) and 2 novel variants (GenBank accession nos. KM265191 and KM265192). In silico DNA topographical studies predicted that KM265192 would have higher cleavage intensity and more accessibility for binding of transcription factors. Even though, similar frequencies were observed for all the variants in all the three study groups, the risk allele 'T' (rs10993994) was seen to be associated with reduced PSP94 expression both at mRNA and protein level. Further, mRNA expression as studied by real-time PCR correlated positively with sPSP94 levels. Interestingly, CC genotype of rs10993994 showed highest sPSP94 levels in all the three study groups and was associated with Gleason score ≤7 in PCa patients. In contrast, TT genotype of rs10993994 was associated with lesser sPSP94 levels and with aggressiveness of PCa.
  
  
  CONCLUSIONS
  rs10993994 was found to be a functional SNP in the studied Asian Indian population.
authors.affiliation: Department of Biochemistry and Clinical Nutrition, Seth G.S. Medical College and K.E.M Hospital, Parel, Mumbai, 400012 India.
authors.forename: Deepa R
authors.initials: DR
authors.lastname: Mhatre
authors.affiliation: Division of Structural Biology, National Institute for Research in Reproductive Health, Jehangir Merwanji Street, Parel, Mumbai, 400012 India.
authors.forename: Smita D
authors.initials: SD
authors.lastname: Mahale
authors.affiliation: Department of Molecular Immunodiagnostics, National Institute for Research in Reproductive Health, Jehangir Merwanji Street, Parel, Mumbai, India.
authors.forename: Mohammed I
authors.initials: MI
authors.lastname: Khatkhatay
authors.affiliation: Division of Structural Biology, National Institute for Research in Reproductive Health, Jehangir Merwanji Street, Parel, Mumbai, 400012 India.
authors.forename: Swati K
authors.initials: SK
authors.lastname: Achrekar
authors.affiliation: Division of Structural Biology, National Institute for Research in Reproductive Health, Jehangir Merwanji Street, Parel, Mumbai, 400012 India.
authors.forename: Swapna S
authors.initials: SS
authors.lastname: Desai
authors.affiliation: Division of Structural Biology, National Institute for Research in Reproductive Health, Jehangir Merwanji Street, Parel, Mumbai, 400012 India.
authors.forename: Dhanashree D
authors.initials: DD
authors.lastname: Jagtap
authors.affiliation: Department of Urology, Seth G.S. Medical College and K.E.M Hospital, Parel, Mumbai, India.
authors.forename: Jayesh V
authors.initials: JV
authors.lastname: Dhabalia
authors.affiliation: Department of Genitourinary Oncology, Tata Memorial Hospital, Parel, Mumbai, India.
authors.forename: Hemant B
authors.initials: HB
authors.lastname: Tongaonkar
authors.affiliation: Department of Biochemistry and Clinical Nutrition, Seth G.S. Medical College and K.E.M Hospital, Parel, Mumbai, 400012 India.
authors.forename: Sucheta P
authors.initials: SP
authors.lastname: Dandekar
authors.affiliation: Department of Biochemistry and Clinical Nutrition, Seth G.S. Medical College and K.E.M Hospital, Parel, Mumbai, 400012 India.
authors.forename: Anand M
authors.initials: AM
authors.lastname: Varadkar
keywords: BPH; Novel variants; PCa; RFLP