Screening of 336 single-nucleotide polymorphisms in 85 obesity-related genes revealed McKusick-Kaufman syndrome gene variants are associated with metabolic syndrome

Genetic factors are important in the development of metabolic syndrome. However, the genetic background of metabolic syndrome remains unclear. We screened polymorphisms in 85 obesity-related genes to determine which may be associated with metabolic syndrome. A total of 336 single-nucleotide polymorphisms (SNPs) in 85 genes selected from the JSNP database were genotyped. We conducted case-control association analyses using patients with metabolic syndrome (n1080) and control individuals (n528) who had no risk of the metabolic syndrome. Three SNPs in the McKusick-Kaufman syndrome (MKKS) gene were significantly related to metabolic syndrome by case-control association study; rs1545 (odds ratio (OR) adjusted for age and gender, 1.45; 95% confidence interval (CI), 1.21-1.74; P0.000043 (additive model)); rs1547 (OR, 1.45; 95% CI, 1.21-1.74; P0.000041); and rs2294901 (OR, 1.46; 95% CI, 1.22-1.75; P0.000033). We selected five tag SNPs (rs2294901, rs221667, rs6133922, rs6077785 and rs6108572) in the MKKS gene. They were in one linkage disequilibrium (LD) block and rs6133922 (P0.00042), rs6077785 (P0.000013) and rs6108572 (P0.000019) as well as rs2294901 were significantly associated with metabolic syndrome. TGAAA haplotype was protective against the metabolic syndrome (P0.0074), and CCGTT haplotype was susceptible (P0.00070) to the metabolic syndrome. Our data suggest that genetic variations at MKKS gene influence the risk of metabolic syndrome.