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PARL, the gene encoding presenilins-associated rhomboid-like protein, maps to chromosome 3q27 within a quantitative trait locus that influences components of the metabolic syndrome. Recently, an amino acid substitution (Leu262Val, rs3732581) in PARL was associated with fasting plasma insulin levels in a US white population (N=1031). This variant was also found to modify the positive association between age and fasting insulin. The aim of this study was to test whether these findings could be replicated in two UK population-based cohorts.Participants from the Medical Research Council Ely and Hertfordshire cohort studies were genotyped for this variant using a SNaPshot primer extension assay and Taqman assay respectively. Full phenotypic and genotypic data were available for 3,666 study participants.Based on a dominant model, we found no association between the Leu262Val polymorphism and fasting insulin levels (p=0.79) or BMI (p=0.98). We did not observe the previously reported interaction between age and genotype on fasting insulin (p=0.14).Despite having greater statistical power, our data do not support the previously reported association between PARL Leu262Val and fasting plasma insulin levels, a measure of insulin resistance. Our findings indicate that this variant is unlikely to be an important contributor to insulin resistance in UK populations.

Original publication

DOI

10.1007/s00125-006-0443-9

Type

Journal article

Journal

Diabetologia

Publication Date

11/2006

Volume

49

Pages

2649 - 2652

Addresses

Metabolic Disease Group, Wellcome Trust Sanger Institute, The Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.

Keywords

Humans, Insulin Resistance, Insulin, Metalloproteases, Leucine, Valine, Mitochondrial Proteins, Body Mass Index, Fasting, Cohort Studies, Amino Acid Substitution, Genotype, Models, Genetic, Aged, Middle Aged, Male, United Kingdom