title: A visfatin promoter polymorphism is associated with low-grade inflammation and type 2 diabetes.
abstract: Visfatin (also known as pre-B cell colony-enhancing factor, or PBEF) is a pro-inflammatory adipokine expressed predominantly in visceral fat. We investigated whether polymorphisms at the visfatin/PBEF locus influence the risk of type 2 diabetes (T2D). Linkage disequilibrium analysis of 52 single nucleotide polymorphisms spanning the entire gene (34.7 kb) plus 20.5 kb of the upstream region and 25.5 kb of the downstream region revealed a single haplotype block that could be tagged by seven single nucleotide polymorphisms. These seven tags were typed in a group of T2D patients (n = 814) and a group of non-diabetic controls (n = 320) of white origin. A significant association was observed at -948C>A, with minor allele frequencies of 0.157 in T2D cases and 0.119 in non-diabetic controls (p = 0.021). In a non-diabetic population (n = 630), the same -948 allele that conferred increased risk of T2D was significantly associated with higher plasma levels of fibrinogen and C-reactive protein (p = 0.0022 and 0.0038, respectively). However, no significant associations were observed with BMI, waist circumference, serum glucose levels, or fasting insulin levels. Our findings suggest that the visfatin/PBEF gene may play a role in determining T2D susceptibility, possibly by modulating chronic, low-grade inflammatory responses.
authors.affiliation: Research Division, Joslin Diabetes Center, Boston, Massachusetts 02215, USA.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Zhang
authors.forename: Lucia
authors.initials: L
authors.lastname: Gottardo
authors.forename: Ryan
authors.initials: R
authors.lastname: Thompson
authors.forename: Christine
authors.initials: C
authors.lastname: Powers
authors.forename: David
authors.initials: D
authors.lastname: Nolan
authors.forename: Jill
authors.initials: J
authors.lastname: Duffy
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Marescotti
authors.forename: Angelo
authors.initials: A
authors.lastname: Avogaro
authors.forename: Alessandro
authors.initials: A
authors.lastname: Doria
mesh_terms: D000328:Adult; D000368:Aged; D015992:Body Mass Index; D016022:Case-Control Studies; D016207:Cytokines / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007249:Inflammation / Q000453:epidemiology / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D054409:Nicotinamide Phosphoribosyltransferase; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D049629:Waist-Hip Ratio
chemical_list: D016207:Cytokines; D054409:Nicotinamide Phosphoribosyltransferase; C085455:nicotinamide phosphoribosyltransferase, human