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Abnormal Lipoprotein(a) Levels Predict Coronary Artery Calcification in East Asian but Not in White Populations*†
222 cohort. H. pylori infection might not be associated with atherogenic lipid pattern. Further studies are needed to confirm or refute the existence of our findings.
141 Identification of a Novel Frame Shift Mutation of the LDL Receptor Gene Causing Familial Hypercholesterolemia in Omani Family* Khalid Ali Al-Waili, MD, Ali Al-Hinai, MD, Abdulrahim Al-Abri, BMSc, Khalid Al-Rasadi, MD, Humood Al-Dhuhli, MD, (Montreal, Quebec) Synopsis: Familial hypercholesterolemia (FH) is an autosomal dominant disease caused commonly by mutation in the low-density lipoprotein receptor (LDLR) gene. It is characterized by a high concentration of low-density lipoprotein cholesterol (LDL-C), and premature coronary artery disease. Purpose: In this study, we report a novel frame shift deletion mutation of the LDL receptor gene in Omani family. Methods: Five patients from the family were screened for mutations in the LDLR gene using direct sequencing of the promoter and 18 exons. Results: The proband was a 10-year-old girl with total cholesterol of 23.2 mmol/L, LDL-C of 22.1 mmol/L, triglyceride 0.8 mmol/L, HDL-C 0.74 mmol/L, ApoB 4.5 g/L, Lpa 1110 mg/L with tendon xanthomas and measured carotid intima media thickness (CIMT) of 1.05 mm. Both the parents and the other two sisters’ ages (13 and 15 years) had high LDL-C 7.1, 6.4, 5.2, and 6.4 mmol/L, respectively. The direct sequencing of the LDL-receptor gene revealed a homozygous frame shift deletion (272delG) of exon 3 in the proband. The parents and the two sisters were heterozygous for this variant. Conclusions: This study identified a novel framshift deletion mutation (272delG) in exon 3 of the LDL receptor gene that causes FH in this Omani family. In Oman the prevalence of FH is not known; therefore, more genetic studies are needed to characterize the molecular basis of FH.
142 Abnormal Lipoprotein(a) Levels Predict Coronary Artery Calcification in East Asian but Not in White Populations*† Abhinav Sharma, MD, Szilard Voros, MD, Parag Joshi, MD, Gustavo Vazquez, MD, Zhen Qian, PhD, Sarah Rinehart, MD, Torrance Laury, BS, Ben Kirkland, BS, Kamran Akram, MD, M. S. Rohman, MD, M. Kasim, MD, (Atlanta, GA) †Encore presentation from Arteriosclerosis, Thrombosis and Vascular Biology Scientific Sessions April 2011 Synopsis: Lipoprotein(a), or Lp(a), has been linked to cardiovascular events in predominantly white populations, although there has not been an association with coronary
Journal of Clinical Lipidology, Vol 5, No 3, June 2011 artery calcification (CAC). Little is known regarding its association with CAC in other ethnicities. Purpose: We hypothesized that Lp(a) measurements would be predictive for the presence of CAC in SE Asian but not in white populations. Methods: A total of 103 patients from the United States (white subjects) and 104 patients from Indonesia (SE Asian subjects) were screened with 64-slice multidetector computed tomography for the presence of any CAC. Standard clinical parameters (age, gender, hypertension, dyslipidemia, diabetes, smoking, lipid profile), and Lp(a) status (normal vs abnormal), were measured. Relationship of standard clinical parameters and Lp(a) status to CAC was assessed by logistic regression, with a P value , .05 considered significant. Net reclassification index was calculated for regression models including Lp(a) status. Results: A total of 1% SE Asian and 37% white subjects had abnormal Lp(a). Calcium was detectable in 40% SE Asians and 63% white subjects. SE Asians were older (56 6 10 vs 52 6 12 years, P 5 .01), and had greater total cholesterol (210 6 45 vs 180 6 47 mg/dL, P , .001), LDL (139 6 40 vs 110643 mg/dL, P , .001), and triglycerides (151 6 95 vs 111 6 56 mg/dL, P 5.007) levels. On multivariable logistic regression analysis, Lp(a) status remained an independent predictor of presence of CAC in SE Asian (P 5 .007) but not in white subjects. The addition of Lp(a) to the regression model for prediction of CAC resulted in significant improvement in AUC, and an NRI of 11.7% in SE Asians. There was no change in Caucasians (Figure).
Conclusions: Lp(a) is associated with coronary arterial calcifications, beyond standard clinical parameters, in SE Asians but not in Caucasians. The underlying mechanisms for this difference remain to be elucidated.
143 Efficacy Readout for PCSK9 Inhibition Reijo Laaksonen, MD, Reini Hurme, PhD, Annik Prat, PhD, Kirill Tarasov, MSc, Kaisa Koistinen, MSc, Nabil Seidah, PhD, Minna J€anis, PhD, (Espoo, Finland)
141 Identification of a Novel Frame Shift Mutation of the LDL Receptor Gene Causing Familial Hypercholesterolemia in Omani Family* Khalid Ali Al-Waili, MD, Ali Al-Hinai, MD, Abdulrahim Al-Abri, BMSc, Khalid Al-Rasadi, MD, Humood Al-Dhuhli, MD, (Montreal, Quebec) Synopsis: Familial hypercholesterolemia (FH) is an autosomal dominant disease caused commonly by mutation in the low-density lipoprotein receptor (LDLR) gene. It is characterized by a high concentration of low-density lipoprotein cholesterol (LDL-C), and premature coronary artery disease. Purpose: In this study, we report a novel frame shift deletion mutation of the LDL receptor gene in Omani family. Methods: Five patients from the family were screened for mutations in the LDLR gene using direct sequencing of the promoter and 18 exons. Results: The proband was a 10-year-old girl with total cholesterol of 23.2 mmol/L, LDL-C of 22.1 mmol/L, triglyceride 0.8 mmol/L, HDL-C 0.74 mmol/L, ApoB 4.5 g/L, Lpa 1110 mg/L with tendon xanthomas and measured carotid intima media thickness (CIMT) of 1.05 mm. Both the parents and the other two sisters’ ages (13 and 15 years) had high LDL-C 7.1, 6.4, 5.2, and 6.4 mmol/L, respectively. The direct sequencing of the LDL-receptor gene revealed a homozygous frame shift deletion (272delG) of exon 3 in the proband. The parents and the two sisters were heterozygous for this variant. Conclusions: This study identified a novel framshift deletion mutation (272delG) in exon 3 of the LDL receptor gene that causes FH in this Omani family. In Oman the prevalence of FH is not known; therefore, more genetic studies are needed to characterize the molecular basis of FH.
142 Abnormal Lipoprotein(a) Levels Predict Coronary Artery Calcification in East Asian but Not in White Populations*† Abhinav Sharma, MD, Szilard Voros, MD, Parag Joshi, MD, Gustavo Vazquez, MD, Zhen Qian, PhD, Sarah Rinehart, MD, Torrance Laury, BS, Ben Kirkland, BS, Kamran Akram, MD, M. S. Rohman, MD, M. Kasim, MD, (Atlanta, GA) †Encore presentation from Arteriosclerosis, Thrombosis and Vascular Biology Scientific Sessions April 2011 Synopsis: Lipoprotein(a), or Lp(a), has been linked to cardiovascular events in predominantly white populations, although there has not been an association with coronary
Journal of Clinical Lipidology, Vol 5, No 3, June 2011 artery calcification (CAC). Little is known regarding its association with CAC in other ethnicities. Purpose: We hypothesized that Lp(a) measurements would be predictive for the presence of CAC in SE Asian but not in white populations. Methods: A total of 103 patients from the United States (white subjects) and 104 patients from Indonesia (SE Asian subjects) were screened with 64-slice multidetector computed tomography for the presence of any CAC. Standard clinical parameters (age, gender, hypertension, dyslipidemia, diabetes, smoking, lipid profile), and Lp(a) status (normal vs abnormal), were measured. Relationship of standard clinical parameters and Lp(a) status to CAC was assessed by logistic regression, with a P value , .05 considered significant. Net reclassification index was calculated for regression models including Lp(a) status. Results: A total of 1% SE Asian and 37% white subjects had abnormal Lp(a). Calcium was detectable in 40% SE Asians and 63% white subjects. SE Asians were older (56 6 10 vs 52 6 12 years, P 5 .01), and had greater total cholesterol (210 6 45 vs 180 6 47 mg/dL, P , .001), LDL (139 6 40 vs 110643 mg/dL, P , .001), and triglycerides (151 6 95 vs 111 6 56 mg/dL, P 5.007) levels. On multivariable logistic regression analysis, Lp(a) status remained an independent predictor of presence of CAC in SE Asian (P 5 .007) but not in white subjects. The addition of Lp(a) to the regression model for prediction of CAC resulted in significant improvement in AUC, and an NRI of 11.7% in SE Asians. There was no change in Caucasians (Figure).
Conclusions: Lp(a) is associated with coronary arterial calcifications, beyond standard clinical parameters, in SE Asians but not in Caucasians. The underlying mechanisms for this difference remain to be elucidated.
143 Efficacy Readout for PCSK9 Inhibition Reijo Laaksonen, MD, Reini Hurme, PhD, Annik Prat, PhD, Kirill Tarasov, MSc, Kaisa Koistinen, MSc, Nabil Seidah, PhD, Minna J€anis, PhD, (Espoo, Finland)