Coriell DNA samples used for validating <i>CYP2D6</i> allele quantification assay.

<p>Coriell DNA samples used for validating <i>CYP2D6</i> allele quantification assay.</p

The mean allelic ratios for <i>CYP2D6</i> gene copy number.

<p>* r = 0.95</p><p>The mean allelic ratios for <i>CYP2D6</i> gene copy number.</p

Scatter plot showing the mean allelic ratios for samples with 2, 3, and 4 <i>CYP2D6</i> gene copy numbers.

<p>Scatter plot showing the mean allelic ratios for samples with 2, 3, and 4 <i>CYP2D6</i> gene copy numbers.</p

<i>CYP2D6</i> genotypes, activity score and predicted phenotypes for samples included in pyrosequencing assay analysis.

<p><i>CYP2D6</i> genotypes, activity score and predicted phenotypes for samples included in pyrosequencing assay analysis.</p

Distribution of CYP2D6 genotypes and phenotypes from 218 PEAR-II clinical samples ¹.

<p>¹ These data were derived based on pyrosequencing and TaqMan copy number assay [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0113808#pone.0113808.ref013" target="_blank">13</a>].</p><p>Distribution of CYP2D6 genotypes and phenotypes from 218 PEAR-II clinical samples <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0113808#t003fn001" target="_blank">¹</a>.</p

Pyrosequencing PCR and sequencing primers for <i>CYP2D6</i>*<i>2</i>, *<i>3</i>, *<i>4</i>, *<i>6</i>*<i>10</i>, *<i>17</i>, *<i>41 alleles</i>.

<p>Pyrosequencing PCR and sequencing primers for <i>CYP2D6</i>*<i>2</i>, *<i>3</i>, *<i>4</i>, *<i>6</i>*<i>10</i>, *<i>17</i>, *<i>41 alleles</i>.</p

Impact of Genetic Polymorphisms of <em>SLC2A2</em>, <em>SLC2A5</em>, and <em>KHK</em> on Metabolic Phenotypes in Hypertensive Individuals

<div><h3>Objective</h3><p>In the past few decades, consumption of added sugars has increased dramatically. Studies have linked high sugar intake with increased risk for a number of diseases. Importantly, fructose, a component of sugar, has been linked with the development of features of metabolic syndrome. This study determined if single nucleotide polymorphisms in genes involved in fructose transport (solute carrier family 2 facilitated glucose transporter, member 2 (<em>SLC2A2</em>) and solute carrier family 2 facilitated glucose/fructose transporter, member 5 (<em>SLC2A5</em>)) and metabolism (ketohexokinase (<em>KHK</em>)) affect inter-individual variability in metabolic phenotypes, such as increased serum uric acid levels.</p> <h3>Materials/Methods</h3><p>The influence of <em>SLC2A2</em>, <em>SLC2A5</em>, and <em>KHK</em> SNPs on metabolic phenotypes was tested in 237 European Americans and 167 African Americans from the Pharmacogenomic Evaluation and Antihypertensive Responses (PEAR) study. Using baseline untreated fasting data, associations were considered significant if p≤0.005. These SNPs were then evaluated for potential replication (p≤0.05) using data from the Genetic Epidemiology of Responses to Antihypertensives (GERA) studies.</p> <h3>Results</h3><p><em>SLC2A5</em> rs5438 was associated with an increase in serum uric acid in European American males. However, we were unable to replicate the association in GERA. The minor allele of <em>SLC2A2</em> rs8192675 showed an association with lower high-density lipoproteins in European Americans (A/A: 51.0 mg/dL, A/G: 47.0 mg/dL, G/G: 41.5 mg/dL, p = 0.0034) in PEAR. The association between rs8192675 and lower high-density lipoproteins was replicated in the combined European American GERA study samples (A/A: 47.6 mg/dL, A/G: 48.6 mg/dL, G/G: 41.9 mg/dL, p = 0.0315).</p> <h3>Conclusions</h3><p>The association between <em>SLC2A2</em> rs8192675 and high-density lipoproteins suggests the polymorphism may play a role in influencing high-density lipoproteins and thus metabolic risk of cardiovascular disease.</p> </div

Baseline characteristics of study populations.

<p>BMI body mass index; DBP diastolic blood pressure (office); HDL high-density lipoprotein; SBP systolic blood pressure (office); LDL low-density lipoprotein; TG triglycerides; SUA serum uric acid. GERA Genetic Epidemiology of Responses to Antihypertensives; PEAR Pharmacogenomic Evaluation and Antihypertensive Responses. Data are given as mean ± standard deviation or n (%).</p

Effects of rs8192675 on HDL levels in PEAR and GERA European Americans.

<p>ANOVA was adjusted for age, BMI, and sex and shown as least square mean ± standard error.</p

Comparison of clinical metabolic parameters for atenolol monotherapy (N = 272) for Caucasians and African Americans.

<p>All variables are presented as mean ± standard deviation.</p><p><b>Δ:</b> difference between baseline and post-treatment.</p><p>AA: African Americans.</p>*<p>C vs. AA: p-value for Caucasians vs. African Americans.</p