Dataset Information

PARL Leu262Val is not associated with fasting insulin levels in UK populations.

ABSTRACT: AIMS/HYPOTHESIS: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. METHODS: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. RESULTS: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). CONCLUSIONS/INTERPRETATION: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.

SUBMITTER: Fawcett KA

PROVIDER: S-EPMC2672784 | biostudies-literature | 2006 Nov

REPOSITORIES: biostudies-literature

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PARL Leu262Val is not associated with fasting insulin levels in UK populations.

Fawcett K A KA Wareham N J NJ Luan J J Syddall H H Cooper C C O'Rahilly S S Day I N M IN Sandhu M S MS Barroso I I

Diabetologia 20060921 11

<h4>Aims/hypothesis</h4>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 the ...[more]

PMID: 17019603

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Project description:OBJECTIVES:We aimed to determine the association between fasting insulin (FI) levels and metabolic syndrome (MetS) in non-diabetic middle-aged and elderly adults in a community in Taiwan. DESIGN:Cross-sectional observational study. SETTING:Community-based investigation in Guishan township of northern Taiwan. PARTICIPANTS:Our study included adults aged 50 years and above during community health examinations between January and October 2014. People with diabetes mellitus were excluded. A total of 321 people were enrolled. OUTCOME MEASURES:We divided participants according to tertiles of FI as low, medium and high levels. Pearson correlation was assessed between insulin level and each of the diagnostic components of metabolic syndrome (MetS-DCs) with adjustment of age. The prevalence of MetS-DCs based on tertiles of FI were studied and analysed by Cochran-Armitage trend test. The risk for prevalence of MetS in the middle and high insulin group as compared with the low insulin group were assessed by multivariate logistic regression with adjustments for age, gender, smoking, body mass index (BMI), hypertension and hyperlipidaemia. Youden Index was performed for the optimised cut-off value. RESULTS:Our results showed positive correlation of FI level with systolic blood pressure, waist circumference, fasting plasma glucose and triglyceride levels, while negative correlation was shown with high-density lipoprotein (P<0.001). The prevalence of each MetS-DCs increased as a trend while FI levels increased (P<0.001). OR (95% CI) of MetS was 5.04 (2.15 to 11.81) for high insulin groups compared with the low insulin group after adjusting confounders (P<0.001). Area under receiver operating characteristic curve (ROC) curve (AUC) was 0.78, and cut-off value 7.35 μU/mL for FI was obtained (sensitivity: 0.69; specificity: 0.77). CONCLUSIONS:Middle-aged and elderly non-diabetic people with increased FI are associated with a higher prevalence of MetS in the community in Taiwan. Furthermore, FI is an independent risk factor of MetS in this study population.

Dataset Information

PARL Leu262Val is not associated with fasting insulin levels in UK populations.

Publications

PARL Leu262Val is not associated with fasting insulin levels in UK populations.

Similar Datasets

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