title: Common variations in the ALMS1 gene do not contribute to susceptibility to type 2 diabetes in a large white UK population.
abstract: OBJECTIVE
  Alström syndrome is a rare monogenic disorder characterised by retinal dystrophy, deafness and obesity. Patients also have insulin resistance, central obesity and dyslipidaemia, thus showing similarities with type 2 diabetes. Rare mutations in the ALMS1 gene cause severe gene disruption in Alström patients; however, ALMS1 gene polymorphisms are common in the general population. The aim of our study was to determine whether common variants in ALMS1 contribute to susceptibility to type 2 diabetes in the UK population.
  
  
  METHODS
  Direct sequencing was performed on coding regions and intron/exon boundaries of the ALMS1 gene in 30 unrelated probands with type 2 diabetes. The linkage disequilibrium (LD; D' and r2) and haplotype structure were examined for the identified variants. The common (minor allele frequency [MAF] >5%) single-nucleotide polymorphisms tagging the common haplotypes (tagged SNPs [tSNPs]) were identified and genotyped in 1985 subjects with type 2 diabetes, 2,047 control subjects and 521 families.
  
  
  RESULTS
  We identified 18 variants with MAF between 6 and 38%. Three SNPs efficiently tagged three common haplotypes (rs1881245, rs3820700 and rs1320374). There was no association (all p > 0.05) between the tSNPs and type 2 diabetes in the case-control study and minor alleles of the tSNPs were not overtransmitted to probands with type 2 diabetes in the family study.
  
  
  CONCLUSIONS
  Common variations in the ALMS1 gene were not associated with type 2 diabetes in a large study of a white UK population.
authors.affiliation: School of Clinical Medical Sciences, University of Newcastle, Newcastle upon Tyne, UK.
authors.forename: S
authors.initials: S
authors.lastname: Patel
authors.forename: J A L
authors.initials: JA
authors.lastname: Minton
authors.forename: M N
authors.initials: MN
authors.lastname: Weedon
authors.forename: T M
authors.initials: TM
authors.lastname: Frayling
authors.forename: C
authors.initials: C
authors.lastname: Ricketts
authors.forename: G A
authors.initials: GA
authors.lastname: Hitman
authors.forename: M I
authors.initials: MI
authors.lastname: McCarthy
authors.forename: A T
authors.initials: AT
authors.lastname: Hattersley
authors.forename: M
authors.initials: M
authors.lastname: Walker
authors.forename: T G
authors.initials: TG
authors.lastname: Barrett
mesh_terms: D000328:Adult; D018797:Cell Cycle Proteins; D003638:Deafness / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D050171:Dyslipidemias / Q000235:genetics; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D013577:Syndrome; D006113:United Kingdom; D044465:White People / Q000235:genetics
chemical_list: C490729:ALMS1 protein, human; D018797:Cell Cycle Proteins; D011506:Proteins