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

Abstract

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 (n¼1080) and control individuals (n¼528) 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; P¼0.000043 (additive model)); rs1547 (OR, 1.45; 95% CI, 1.21-1.74; P¼0.000041); and rs2294901 (OR, 1.46; 95% CI, 1.22-1.75; P¼0.000033). 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 (P¼0.00042), rs6077785 (P¼0.000013) and rs6108572 (P¼0.000019) as well as rs2294901 were significantly associated with metabolic syndrome. TGAAA haplotype was protective against the metabolic syndrome (P¼0.0074), and CCGTT haplotype was susceptible (P¼0.00070) to the metabolic syndrome. Our data suggest that genetic variations at MKKS gene influence the risk of metabolic syndrome.

Exploration of the cognitive, adaptive and behavioral functioning of patients affected with Bardet–Biedl syndrome

“…Of the 150 genes which have been identified with ASD risk factors variants at least 6 relate to BBS. This includes BBS10 which, along with BBS1 , is the gene most frequently mutated in our cohort of patients . In this study, six out of seven of our patients with BBS10 mutations and four out of five with BBS1 mutations had significant ASD symptoms.…”

Kuwaiti population subgroup of nomadic Bedouin ancestry—Whole genome sequence and analysis

“…All these three variants carry the risk allele. Abnormal waist circumference (134 cm): The deleterious variant rs1919128 (C2orf16) is associated with the bivariate trait of waist circumference—triglycerides (WC-TG) [31] , and rs1545 (MKKS) is associated with the metabolic syndrome of abdominal obesity [32] . Bronchial asthma: The deleterious variant rs1051931 (PLA2G7) is associated with susceptibility to asthma [33] .…”

“…Abnormal waist circumference (134 cm): The deleterious variant rs1919128 (C2orf16) is associated with the bivariate trait of waist circumference—triglycerides (WC-TG) [31] , and rs1545 (MKKS) is associated with the metabolic syndrome of abdominal obesity [32] .…”

Association of variations in the FTO, SCG3 and MTMR9 genes with metabolic syndrome in a Japanese population

“…Metabolic syndrome was diagnosed as reported previously. 11,23 In brief, metabolic syndrome is defined by the presence of two or more metabolic abnormalities in addition to obesity (body mass index 425 kg m À2 ). The metabolic abnormalities were as follows: (1) triglyceride level X150 mg per 100 ml and/or high-density lipoprotein cholesterol level o40 mg per 100 ml, or under treatment for this type of dyslipidemia; (2) systolic blood pressure X130 mm Hg and/or diastolic blood pressure blood pressure X85 mm Hg, or under treatment for hypertension; and (3) fasting glucose level X110 mg per 100 ml, or under treatment for diabetes.…”

“…3,4 Results from studies using twins and families have suggested that genetic and environmental factors contribute to the clustering of metabolic abnormalities in various ethnic groups. [5][6][7][8][9][10] We determined in a previous study that four single-nucleotide polymorphisms (SNPs) (rs2294901, rs6133922, rs6077785 and rs6108572) in the McKusickKaufman syndrome (MKKS) gene were significantly associated with metabolic syndrome in the Japanese population 11 by screening SNPs in 85 obesity-related genes that had been reported as of 2005. 12 We carried out a large-scale case-control association study and found that secretogranin III (SCG3) 13 and myotubularin-related protein 9 (MTMR9) 14 conferred susceptibility to the obesity phenotype in the Japanese population.…”