title: Common promoter polymorphism in monocyte differentiation antigen CD14 is associated with serum triglyceride levels and body mass index in non-diabetic individuals.
abstract: OBJECTIVE
  Growing evidence supports the hypothesis that chronic low-grade inflammation related to innate immunity may play an important role in the pathophysiology of Type 2 diabetes mellitus (T2DM). The monocyte differentiation antigen CD14 gene (CD14) acts as the receptor for lipopolysaccharide (LPS) and augments monocyte/macrophage inflammatory responses.
  
  
  METHODS
  We have sequenced the gene, including all exons, exon/intron boundaries, and the -1.5 kb of the 5' flanking region. Two common loci (minor allele frequency > 0.05) were genotyped in 775 T2DM patients and 316 control subjects recruited in the Korean T2DM Study.
  
  
  RESULTS
  Eight polymorphisms, including four non-synonymous forms, were identified in CD14. No polymorphisms were found in association with T2DM. However, one common promoter SNP (-260T>C) was significantly associated with both the serum triglyceride level (TG) and body mass index (BMI) in non-diabetic control subjects. Individuals who carried the minor allele (C) had higher TG levels (1.65 +/- 0.81 vs. 1.46 +/- 0.80 mmol/l; P = 0.0007) and BMI (23.96 +/- 3.00 vs. 23.28 +/- 3.22 kg/m(2); P = 0.04) as compared with subjects carrying T/T genotypes.
  
  
  CONCLUSIONS
  Our data suggest that lipid metabolism and obesity, important pathophysiological elements of T2DM and the metabolic syndrome, are regulated by complex mechanisms that include the CD14 gene polymorphism-mediated genetic propensity to non-specific inflammatory responses.
authors.affiliation: Department of Genetic Epidemiology, SNP Genetics, Inc., Seoul, Korea.
authors.forename: H D
authors.initials: HD
authors.lastname: Shin
authors.forename: K S
authors.initials: KS
authors.lastname: Park
authors.forename: B L
authors.initials: BL
authors.lastname: Park
authors.forename: H S
authors.initials: HS
authors.lastname: Cheong
authors.forename: Y M
authors.initials: YM
authors.lastname: Cho
authors.forename: H K
authors.initials: HK
authors.lastname: Lee
authors.forename: J-Y
authors.initials: JY
authors.lastname: Lee
authors.forename: J-K
authors.initials: JK
authors.lastname: Lee
authors.forename: H T
authors.initials: HT
authors.lastname: Kim
authors.forename: B G
authors.initials: BG
authors.lastname: Han
authors.forename: J W
authors.initials: JW
authors.lastname: Kim
authors.forename: I
authors.initials: I
authors.lastname: Koh
authors.forename: Y J
authors.initials: YJ
authors.lastname: Kim
authors.forename: B
authors.initials: B
authors.lastname: Oh
authors.forename: K
authors.initials: K
authors.lastname: Kimm
authors.forename: C
authors.initials: C
authors.lastname: Park
mesh_terms: D001483:Base Sequence; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006801:Humans; D007438:Introns / Q000235:genetics; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014280:Triglycerides / Q000097:blood*
chemical_list: D018950:Lipopolysaccharide Receptors; D014280:Triglycerides