TAILIEUCHUNG - Báo cáo Y học: Human bile salt-stimulated lipase has a high frequency of size variation due to a hypervariable region in exon 11

The apparent molecular mass of human milk bile salt-stimulated lipase (BSSL) varies between mothers. The molecular basis for this is unknown, but indirect evidence has suggested the di erences to reside in a region of repeats located in the C-terminal part of the protein. We here report that a polymorphism within exon 11 of the BSSLgene is the explanation for the molecular variants of BSSL found in milk. | Eur. J. Biochem. 269 759-767 2002 FEBS 2002 Human bile salt-stimulated lipase has a high frequency of size variation due to a hypervariable region in exon 11 Susanne Lindquist1 Lars Blackberg2 and Olle Hernell1 Departments ofIClinical Sciences Pediatrics and 2Medical Biosciences Medical Biochemistry Umea University Sweden The apparent molecular mass of human milk bile salt-stimulated lipase BSSL varies between mothers. The molecular basis for this is unknown but indirect evidence has suggested the differences to reside in a region of repeats located in the C-terminal part of the protein. We here report that a polymorphism within exon 11 of the BSSL gene is the explanation for the molecular variants of BSSL found in milk. By Southern blot hybridization we analyzed the BSSL gene from mothers known to have BSSL of different molecular masses in their milk. A polymorphism was found within exon 11 previously shown to consist of 16 near identical repeats of 33 bp each. We detected deletions or in one case an insertion corres ponding to the variation in molecular mass of the BSSL protein found in milk from the respective woman. Furthermore we found that 56 out of 295 individuals studied carry deletions or insertions within exon 11 in one or both alleles of the BSSL gene. Hence this is a hypervariable region and the current understanding that exon 11 in the human BSSL gene encodes 16 repeats is an over-simplifcation and needs to be revisited. Natural variation in the molecular mass of BSSL may have clinical implications. Keywords BSSL lipase human milk repeats polymorphism. Bile salt-stimulated lipase BSSL or carboxyl ester lipase is a digestive enzyme secreted from exocrine pancreas in all species examined. BSSL has a broad substrate specificity and contributes to the hydrolysis of dietary mono- di- and tri-acylglycerols and is responsible for digestion of fat-soluble vitamin esters and cholesterol esters in the small intestine. In some species including humans the gene is

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