Minor allele frequency of significant SNPs.

<p>rs no, NCBI Reference SNP (rs) Number, an identification tag assigned by NCBI to SNPs.</p><p>Chr, Chromosome.</p><p>p-value obtained by comparing frequencies using Chi-Square Test.</p><p>MAF (Total), minor allele frequency obtained from total sum of case and control subjects in this study.</p><p>MAF (PD), minor allele frequency information from public database, NCBI dbSNP Build 137.</p

Comparison of clinical profiles between rs12084215 genotypes among Control subjects.

<p>Data are presented in mean ± SD.</p><p>p-values were obtained by comparing the phenotypes among the genotypes using Analysis of Variance (ANOVA).</p

Comparison of clinical profiles between rs57825321 genotypes among FH patients.

<p>Data are presented in mean ± SD.</p><p>p-values were obtained by comparing the phenotypes among the genotypes using Analysis of Variance (ANOVA).</p

Comparison of clinical profiles between rs12084215 genotypes among FH patients.

<p>Data are presented in mean ± SD.</p><p>p-values were obtained by comparing the phenotypes among the genotypes using Analysis of Variance (ANOVA).</p

Genetic Polymorphisms in <i>LDLR</i>, <i>APOB</i>, <i>PCSK9</i> and Other Lipid Related Genes Associated with Familial Hypercholesterolemia in Malaysia

<div><p>Familial hypercholesterolemia (FH) is an autosomal dominant disorder characterized by elevations in total cholesterol (TC) and low density lipoprotein cholesterol (LDLc). Development of FH can result in the increase of risk for premature cardiovascular diseases (CVD). FH is primarily caused by genetic variations in <i>Low Density Lipoprotein Receptor</i> (<i>LDLR</i>), <i>Apolipoprotein B</i> (<i>APOB</i>) or <i>Proprotein Convertase Subtilisin/Kexin type 9</i> (<i>PCSK9</i>) genes. Although FH has been extensively studied in the Caucasian population, there are limited reports of FH mutations in the Asian population. We investigated the association of previously reported genetic variants that are involved in lipid regulation in our study cohort. A total of 1536 polymorphisms previously implicated in FH were evaluated in 141 consecutive patients with clinical FH (defined by the Dutch Lipid Clinic Network criteria) and 111 unrelated control subjects without FH using high throughput microarray genotyping platform. Fourteen Single Nucleotide Polymorphisms (SNPs) were found to be significantly associated with FH, eleven with increased FH risk and three with decreased FH risk. Of the eleven SNPs associated with an increased risk of FH, only one SNP was found in the <i>LDLR</i> gene, seven in the <i>APOB</i> gene and three in the <i>PCSK9</i> gene. SNP rs12720762 in <i>APOB</i> gene is associated with the highest risk of FH (odds ratio 14.78, p<0.001). Amongst the FH cases, 108 out of 141 (76.60%) have had at least one significant risk-associated SNP. Our study adds new information and knowledge on the genetic polymorphisms amongst Asians with FH, which may serve as potential markers in risk prediction and disease management.</p> </div

Demographics and clinical profiles of the subjects.

<p>BMI, Body Mass Index.</p><p>WC, Waist circumference.</p><p>TG, Triglyceride.</p><p>TC, Total Cholesterol.</p><p>HDLc, High Density Lipoprotein Cholesterol.</p><p>LDLc, Low Density Lipoprotein Cholesterol.</p><p>The data are expressed as mean (±SD).</p><p>p-values were obtained by comparing the phenotypes between the two groups using Student’s t-test.</p

Comparison of clinical profiles between rs12720772 genotypes among FH patients.

<p>Data are presented in mean ± SD.</p><p>p-values were obtained by comparing the phenotypes among the genotypes using Analysis of Variance (ANOVA).</p

Comparison of clinical profiles between rs13306194 genotypes among FH patients.

<p>Data are presented in mean ± SD.</p><p>p-values were obtained by comparing the phenotypes among the genotypes using Analysis of Variance (ANOVA).</p

FH associated SNPs, (p<0.05).

<p>rs number, NCBI Reference SNP (rs) Number, an identification tag assigned by NCBI to SNPs <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0060729#pone.0060729-Sherry1" target="_blank">[30]</a>.</p><p>CI, Confidence interval.</p><p>Odds ratio (OR) between groups was determined by logistic regression.</p