16 research outputs found
Aplipoprotein E genotyping: accurate, simple, high throughput method using ABI Prism® SNaPshot™ Multiplex System
No full textINSULIN RECEPTOR SUBSTRATE 1 GENE VARIATION MODIFIES INSULIN RESISTANCE RESPONSE TO VARIOUS TYPES OF DIETARY STRATEGIES: RESULTS FROM THE DIRECT INTERVENTION TRIAL
No full textClinical-biochemical correlation in molecularly characterized patients with Niemann-Pick type C
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CETP genotype and changes in lipid levels in response to weight-loss diet intervention in the POUNDS LOST and DIRECT randomized trials
No full textLittle is known about whether cholesteryl ester transfer protein (CETP) genetic variation may modify the effect of weight-loss diets varying in fat content on changes in lipid levels. We analyzed the interaction between the CETP variant rs3764261 and dietary interventions on changes in lipid levels among 732 overweight/obese adults from a 2 year randomized weight-loss trial [Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST)], and replicated the findings in 171 overweight/obese adults from an independent 2 year weight-loss trial [Dietary Intervention Randomized Controlled Trial (DIRECT)]. In the POUNDS LOST, participants with the CETP rs3764261 CC genotype on the high-fat diet had larger increases in HDL cholesterol (P = 0.001) and decreases in triglycerides (P = 0.007) than those on the low-fat diet at 6 months, while no significant difference between these two diets was observed among participants carrying other genotypes. The gene-diet interactions on changes in HDL-cholesterol and tri-glyc-erides were replicated in the DIRECT (pooled P for interaction ≤ 0.01). Similar results on trajectory of changes in HDL cholesterol and triglycerides over the 2 year intervention were observed in both trials. Our study provides replicable evidence that individuals with the CETP rs3764261 CC genotype might derive greater effects on raising HDL cholesterol and lowering triglycerides by choosing a low-carbohydrate/high-fat weight-loss diet instead of a low-fat diet.Version of Recor
Recent Origin and Spread of a Common Lithuanian Mutation, G197del LDLR, Causing Familial Hypercholesterolemia: Positive Selection Is Not Always Necessary to Account for Disease Incidence among Ashkenazi Jews
No full textG197del is the most prevalent LDL receptor (LDLR) mutation causing familial hypercholesterolemia (FH) in Ashkenazi Jew (AJ) individuals. The purpose of this study was to determine the origin, age, and population distribution of G197del, as well as to explore environmental and genetic effects on disease expression. Index cases from Israel (n=46), South Africa (n=24), Russia (n=7), The Netherlands (n=1), and the United States (n=1) were enlisted. All trace their ancestry to Lithuania. A highly conserved haplotype (D19S221:104-D19S865:208-D19S413:74) was identified in G197del chromosomes, suggesting the occurrence of a common founder. When two methods were used for analysis of linkage disequilibrium (LD) between flanking polymorphic markers and the disease locus and for the study of the decay of LD over time, the estimated age of the deletion was found to be 20 ± 7 generations (the 95% confidence interval is 15–26 generations), so that the most recent common ancestor of the mutation-bearing chromosomes would date to the 14th century. This corresponds with the founding of the Jewish community of Lithuania (1338 a.d.), as well as with the great demographic expansion of AJ individuals in eastern Europe, which followed this settlement. The penetrance of mutation-linked severe hypercholesterolemia is high (94% of heterozygotes have a baseline concentration of LDL cholesterol (LDL-C) that is >160 mg/dl), and no significant differences in the mean baseline lipid level of G197del carriers from different countries were found. Polymorphisms of apolipoprotein E and of scavenger-receptor class B type I were observed to have minor effects on the plasma lipid profile. With respect to determinative genetic influences on the biochemical phenotype, there is no evidence that could support the possibility of a selective evolutionary metabolic advantage. Therefore, the founder effect in a rapidly expanding population from a limited number of families remains a simple, parsimonious hypothesis explaining the spread of G197del-LDLR–linked FH in AJ individuals
Evaluating an mRNA based body fluid identification test using SYBR green fluorescent dye and real-time PCR
No full textThe requirement to have more definitive and wider ranging body fluid identification (BFID) tests has resulted in a range of mRNA based real-time PCR BFI assays utilising Taqman fluorescent dye. An attempt to make a reliable and cost effective BFI test utilising the alternative SYBR Green fluorescent dye was carried out. RNA was extracted from blood and saliva stains from both male and female donors, this was then reverse transcribed using M-MLV and random hexamers. Using real-time PCR, relative quantitation of blood and saliva specific markers was carried out on the cDNA from the blood and saliva samples using the SYBR® Green fluorescent dye. Melting curve analysis was also performed immediately following PCR amplification. The relative quantitation values were calculated using the formula 2-ΔΔCT and all samples were normalised to reference gene 18s rRNA. The results revealed good specificity for a number of markers using this chemistry, however some markers were undetected. Blood markers NCF2, SPTB, PBDG and saliva specific markers HTN3, SPRR1A, KRT4 and KRT13 were investigated. In the SYBR green studies, the most specific markers were NCF2, KRT4, KRT13 and SPRR1A, showing reproducible results in a number of studies. Blood marker SPTB also appeared to be specific to blood however the melt curve data for this marker in each study was questionable given the low melting temperature for the amplified products. Blood specific marker PBGD, and saliva specific marker HTN3 were not detected using SYBR Green and saliva marker STATH was detected however in each case appeared to be non-specific in nature when them melt curves were analysed. Analysis of the 18s rRNA Ct values showed a higher expression in saliva than in blood in almost all instances, this may be due to collection of a higher number of cells when using a buccal swab, coupled with the inability to accurately quantify the RNA extracts before reverse transcription. Taqman assays were run on all markers as an additional test, to compare with the SYBR green data. All markers except SPTB showed very good specificity for their respective body fluids. SPTB, like in the SYBR green studies was detected in blood more than saliva, however detection was never consistent in each sample. It can therefore be said that real-time PCR using SYBR Green dye was capable of identifying specific mRNA markers blood and saliva however, the lack of specificity for this type of assay makes its use as a routine identification of body fluids in forensic casework not suitable. The main aim of this study was to develop a more cost effective BFID and as such involved the use of SYBR Green as a cheaper alternative to TaqMan. However, throughout these studies, it appeared to be quite costly in terms of validating a SYBR Green experiment, as more reagents were required in the long run due to vast amount of no template controls required per experiment. It therefore would appear that while SYBR Green is cheaper to buy, the cost to validate these type of experiments can be quite high, due to the non-specific nature of the dye itself. The SYBR Green studies were also much more time consuming with regards to data interpretation as post analysis of the amplification plot and melt curves is a necessity with this detection chemistry to ensure successful interpretation of the data
A Cholesterol-Lowering Gene Maps to Chromosome 13q
No full textSummaryA cholesterol-lowering gene has been postulated from familial hypercholesterolemia (FH) families having heterozygous persons with normal LDL levels and homozygous individuals with LDL levels similar to those in persons with heterozygous FH. We studied such a family with FH that also had members without FH and with lower-than-normal LDL levels. We performed linkage analyses and identified a locus at 13q, defined by markers D13S156 and D13S158. FASTLINK and GENEHUNTER yielded LOD scores >5 and >4, respectively, whereas an affected-sib-pair analysis gave a peak multipoint LOD score of 4.8, corresponding to a P value of 1.26×10−6. A multipoint quantitative-trait-locus (QTL) linkage analysis with maximum-likelihood binomial QTL verified this locus as a QTL for LDL levels. To test the relevance of this QTL in an independent normal population, we studied MZ and DZ twin subjects. An MZ-DZ comparison confirmed genetic variance with regard to lipid concentrations. We then performed an identity-by-descent linkage analysis on the DZ twins, with markers at the 13q locus. We found strong evidence for linkage at this locus with LDL (P<.0002), HDL (P<.004), total cholesterol (P<.0002), and body-mass index (P<.0001). These data provide support for the existence of a new gene influencing lipid concentrations in humans
Global perspective of familial hypercholesterolaemia: a cross-sectional study from the EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC)
No full textEAS Familial Hypercholesterolaemia Studies Collaboration (FHSC): Antonio J Vallejo-Vaz, Christophe A T Stevens, Alexander R M Lyons, Kanika I Dharmayat, Tomas Freiberger, G Kees Hovingh, Pedro Mata, Frederick J Raal, Raul D Santos, Handrean Soran, Gerald F Watts, Marianne Abifadel, Carlos A Aguilar-Salinas, Khalid F Alhabib, Mutaz Alkhnifsawi, Wael Almahmeed, Fahad Alnouri, Rodrigo Alonso, Khalid Al-Rasadi, Ahmad Al-Sarraf, Nasreen Al-Sayed, Francisco Araujo, Tester F Ashavaid, Maciej Banach, Sophie Béliard, Marianne Benn, Christoph J Binder, Martin P Bogsrud, Mafalda Bourbon, Krzysztof Chlebus, Pablo Corral, Kairat Davletov, Olivier S Descamps, Ronen Durst, Marat Ezhov, Dan Gaita, Jacques Genest, Urh Groselj, Mariko Harada-Shiba, Kirsten B Holven, Meral Kayikcioglu, Weerapan Khovidhunkit, Katarina Lalic, Gustavs Latkovskis, Ulrich Laufs, Evangelos Liberopoulos, Marcos M Lima-Martinez, Jie Lin, Vincent Maher, A David Marais, Winfried März, Erkin Mirrakhimov, André R Miserez, Olena Mitchenko, Hapizah Nawawi, Børge G Nordestgaard, Andrie G Panayiotou, György Paragh, Zaneta Petrulioniene, Belma Pojskic, Arman Postadzhiyan, Katarina Raslova, Ashraf Reda, Željko Reiner, Fouzia Sadiq, Wilson Ehidiamen Sadoh, Heribert Schunkert, Aleksandr B Shek, Mario Stoll, Erik Stroes, Ta-Chen Su, Tavintharan Subramaniam, Andrey V Susekov, Myra Tilney, Brian Tomlinson, Thanh Huong Truong, Alexandros D Tselepis, Anne Tybjærg-Hansen, Alejandra Vázquez Cárdenas, Margus Viigimaa, Luya Wang, Shizuya Yamashita, John J P Kastelein, Eric Bruckert, Branislav Vohnout, Laura Schreier, Jing Pang, Christoph Ebenbichler, Hans Dieplinger, Reinhold Innerhofer, Yvonne Winhofer-Stöckl, Susanne Greber-Platzer, Konstantin Krychtiuk, Walter Speidl, Hermann Toplak, Kurt Widhalm, Thomas Stulnig, Kurt Huber, Florian Höllerl, Gersina Rega-Kaun, Lucas Kleemann, Martin Mäser, Sabine Scholl-Bürgi, Christoph Säly, Florian J Mayer, Gaelle Sablon, Eric Tarantino, Charlotte Nzeyimana, Lamija Pojskic, Ibrahim Sisic, Azra D Nalbantic, Cinthia E Jannes, Alexandre C Pereira, Jose E Krieger, Ivo Petrov, Assen Goudev, Fedya Nikolov, Snejana Tisheva, Yoto Yotov, Ivajlo Tzvetkov, Alexis Baass, Jean Bergeron, Sophie Bernard, Diane Brisson, Liam R Brunham, Lubomira Cermakova, Patrick Couture, Gordon A Francis, Daniel Gaudet, Robert A Hegele, Etienne Khoury, G B John Mancini, Brian W McCrindle, Martine Paquette, Isabelle Ruel, Ada Cuevas, Sylvia Asenjo, Xumin Wang, Kang Meng, Xiantao Song, Qiang Yong, Tao Jiang, Ziyou Liu, Yanyu Duan, Jing Hong, Pucong Ye, Yan Chen, Jianguang Qi, Zesen Liu, Yuntao Li, Chaoyi Zhang, Jie Peng, Ya Yang, Wei Yu, Qian Wang, Hui Yuan, Shitong Cheng, Long Jiang, Mei Chong, Jian Jiao, Yue Wu, Wenhui Wen, Liyuan Xu, Ruiying Zhang, Yichen Qu, Jianxun He, Xuesong Fan, Zhenjia Wang, Elaine Chow, Ivan Pećin, Dražen Perica, Phivos Symeonides, Michal Vrablik, Richard Ceska, Vladimir Soska, Lukas Tichy, Vera Adamkova, Jana Franekova, Renata Cifkova, Pavel Kraml, Katerina Vonaskova, Jana Cepova, Magdalena Dusejovska, Lenka Pavlickova, Vladimir Blaha, Hana Rosolova, Barbora Nussbaumerova, Roman Cibulka, Helena Vaverkova, Lubica Cibickova, Zdenka Krejsova, Katerina Rehouskova, Pavel Malina, Milena Budikova, Vaclava Palanova, Lucie Solcova, Alena Lubasova, Helena Podzimkova, Juraj Bujdak, Jiri Vesely, Marta Jordanova, Tomas Salek, Robin Urbanek, Stanislav Zemek, Jan Lacko, Hana Halamkova, Sona Machacova, Sarka Mala, Eva Cubova, Katerina Valoskova, Lukas Burda, Ahmed Bendary, Ihab Daoud, Sameh Emil, Atef Elbahry, Samir Rafla, Osama Sanad, Ghada Kazamel, Mohamed Ashraf, Mohamed Sobhy, Amro El-Hadidy, Mohamed A Shafy, Saif Kamal, Mohamed Bendary, Grete Talviste, Denis Angoulvant, Franck Boccara, Bertrand Cariou, Valérie Carreau, Alain Carrie, Sybil Charrieres, Yves Cottin, Mathilde Di-Fillipo, Pierre H Ducluzeau, Sonia Dulong, Vincent Durlach, Michel Farnier, Emile Ferrari, Dorota Ferrieres, Jean Ferrieres, Antonio Gallo, Regis Hankard, Jocelyne Inamo, Julie Lemale, Philippe Moulin, François Paillard, Noel Peretti, Agnès Perrin, Alain Pradignac, Jean P Rabes, Vincent Rigalleau, Ariane Sultan, François Schiele, Patrick Tounian, René Valero, Bruno Verges, Cécile Yelnik, Olivier Ziegler, Ira A Haack, Nina Schmidt, Alexander Dressel, Isabel Klein, Jutta Christmann, Antonia Sonntag, Christine Stumpp, Diana Boger, Dana Biedermann, Monica M N Usme, F Ulrich Beil, Gerald Klose, Christel König, Ioanna Gouni-Berthold, Britta Otte, Gereon Böll, Anja Kirschbaum, Jürgen Merke, Johannes Scholl, Thomas Segiet, Marco Gebauer, Florentina Predica, Manfred Mayer, Frank Leistikow, Sabine Füllgraf-Horst, Cornelius Müller, Melanie Schüler, Judith Wiener, Konrad Hein, Peter Baumgartner, Stefan Kopf, Reinhold Busch, Michael Schömig, Stephan Matthias, Nicole Allendorf-Ostwald, Bruno Fink, Dieter Böhm, Alexander Jäkel, Ann-Cathrin Koschker, Rüdiger Schweizer, Anja Vogt, Klaus Parhofer, Wolfgang König, Wibke Reinhard, Andrea Bäßler, Alexander Stadelmann, Volker Schrader, Julius Katzmann, Adrienne Tarr, Elisabeth Steinhagen-Thiessen, Ursula Kassner, Gerret Paulsen, Jürgen Homberger, Claudia Zemmrich, Wolfgang Seeger, Kathrin Biolik, Dorothee Deiss, Corinna Richter, Elina Pantchechnikova, Elena Dorn, Ulrike Schatz, Ulrich Julius, Antje Spens, Tobias Wiesner, Michael Scholl, Christos V Rizos, Nikolaos Sakkas, Moses Elisaf, Ioannis Skoumas, Konstantinos Tziomalos, Loukianos Rallidis, Vasileios Kotsis, Michalis Doumas, Vasileios Athyros, Emmanouil Skalidis, Genovefa Kolovou, Anastasia Garoufi, Eleni Bilianou, Iosif Koutagiar, Dimitrios Agapakis, Estela Kiouri, Christina Antza, Niki Katsiki, Evangelos Zacharis, Achilleas Attilakos, George Sfikas, Charalambos Koumaras, Panagiotis Anagnostis, Georgia Anastasiou, George Liamis, Amalia-Despoina Koutsogianni, Zsolt Karányi, Mariann Harangi, László Bajnok, Mária Audikovszky, László Márk, Béla Benczúr, István Reiber, Gergely Nagy, András Nagy, Lakshmi L Reddy, Swarup A V Shah, Chandrashekhar K Ponde, Jamshed J Dalal, Jitendra P S Sawhney, Ishwar C Verma, Mays Altaey, Khalid Al-Jumaily, Dilshad Rasul, Ali F Abdalsahib, Amer A Jabbar, Mohanad Al-Ageedi, Ruth Agar, Hofit Cohen, Avishay Ellis, Dov Gavishv, Dror Harats, Yaacov Henkin, Hila Knobler, Leah Leavit, Eran Leitersdorf, Ardon Rubinstein, Daniel Schurr, Shoshi Shpitzen, Auryan Szalat, Manuela Casula, Veronica Zampoleri, Marta Gazzotti, Elena Olmastroni, Riccardo Sarzani, Claudio Ferri, Elena Repetti, Carlo Sabbà, Antonio Carlo Bossi, Claudio Borghi, Sandro Muntoni, Francesco Cipollone, Francesco Purrello, Arturo Pujia, Angelina Passaro, Rossella Marcucci, Valerio Pecchioli, Livia Pisciotta, Giuseppe Mandraffino, Fabio Pellegatta, Giuliana Mombelli, Adriana Branchi, Anna Maria Fiorenza, Cristina Pederiva, Josè Pablo Werba, Gianfranco Parati, Francesca Carubbi, Lorenzo Iughetti, Arcangelo Iannuzzi, Gabriella Iannuzzo, Paolo Calabrò, Maurizio Averna, Giacomo Biasucci, Sabina Zambon, Anna Rita Roscini, Chiara Trenti, Marcello Arca, Massimo Federici, Maria Del Ben, Andrea Bartuli, Andrea Giaccari, Antonio Pipolo, Nadia Citroni, Ornella Guardamagna, Katia Bonomo, Andrea Benso, Gianni Biolo, Lorenzo Maroni, Alessandro Lupi, Luca Bonanni, Maria Grazia Zenti, Kota Matsuki, Mika Hori, Masatsune Ogura, Daisaku Masuda, Takuya Kobayashi, Kumiko Nagahama, Mohammed Al-Jarallah, Mirjana Radovic, Olga Lunegova, Erkayim Bektasheva, Elyor Khodzhiboboev, Andrejs Erglis, Dainus Gilis, Georgijs Nesterovics, Vita Saripo, Ruta Meiere, Arta Upena-RozeMicena, Elizabete Terauda, Selim Jambart, Petra E Khoury, Sandy Elbitar, Carine Ayoub, Youmna Ghaleb, Urte Aliosaitiene, Sandra Kutkiene, Noor A M Kasim, Noor S M Nor, Anis S Ramli, Suraya A Razak, Alyaa Al-Khateeb, Siti H S A Kadir, Suhaila A Muid, Thuhairah A Rahman, Sazzli S Kasim, Ahmad B M Radzi, Khairul S Ibrahim, Salmi Razali, Zaliha Ismail, Rohana A Ghani, Muhammad I A Hafidz, Ang L Chua, Marshima M Rosli, Muthukkaruppan Annamalai, Lay K Teh, Rafezah Razali, Yung A Chua, Azhari Rosman, Abdul R Sanusi, Nor A A Murad, A Rahman A Jamal, Sukma A Nazli, Aimi Z Razman, Norhidayah Rosman, Radzi Rahmat, Nur S Hamzan, C Azzopardi, Roopa Mehta, Alexandro J Martagon, Gabriela A G Ramirez, Neftali E A Villa, Arsenio V Vazquez, Daniel Elias-Lopez, Gustavo G Retana, Betsabel Rodriguez, Jose J C Macías, Alejandro R Zazueta, Rocio M Alvarado, Julieta D M Portano, Humberto A Lopez, Leobardo Sauque-Reyna, Laura G G Herrera, Luis E S Mendia, Humberto Garcia Aguilar, Elizabeth R Cooremans, Berenice P Aparicio, Victoria M Zubieta, Perla A C Gonzalez, Aldo Ferreira-Hermosillo, Nacu C Portilla, Guadalupe J Dominguez, Alinna Y R Garcia, Hector E A Cazares, Jesus R Gonzalez, Carla V M Valencia, Francisco G Padilla, Ramon M Prado, Manuel O De Los Rios Ibarra, Ruy D A Villicaña, Karina J A Rivera, Ricardo A Carrera, Jose A Alvarez, Jose C A Martinez, Manuel de Los Reyes Barrera Bustillo, Gonzalo C Vargas, Roberto C Chacon, Mario H F Andrade, Ashanty F Ortega, Hector G Alcala, Laura E G de Leon, Berenice G Guzman, Jose J G Garcia, Juan C G Cuellar, Jose R G Cruz, Anell Hernandez Garcia, Jesus R H Almada, Ursulo J Herrera, Fabiola L Sobrevilla, Eduardo M Rodriguez, Cristina M Sibaja, Alma B M Rodriguez, Jose C M Oyervides, Daniel I P Vazquez, Eduardo A R Rodriguez, Ma L R Osorio, Juan R Saucedo, Margarita T Tamayo, Luis A V Talavera, Luis E V Arroyo, Eloy A Z Carrillo, Alphonsus Isara, Darlington E Obaseki, Khalid Al-Waili, Fahad Al-Zadjali, Ibrahim Al-Zakwani, Mohammed Al-Kindi, Suad Al-Mukhaini, Hamida Al-Barwani, Asim Rana, Lahore S U Shah, Ewa Starostecka, Agnieszka Konopka, Joanna Lewek, Marcin Bartłomiejczyk, Mariusz Gąsior, Krzysztof Dyrbuś, Jacek Jóźwiak, Marcin Gruchała, Marcin Pajkowski, Marzena Romanowska-Kocejko, Marta Żarczyńska-Buchowiecka, Magdalena Chmara, Bartosz Wasąg, Aleksandra Parczewska, Natasza Gilis-Malinowska, Justyna Borowiec-Wolna, Aneta Stróżyk, Marlena Woś, Aleksandra Michalska-Grzonkowska, Ana M Medeiros, Ana C Alves, Francisco Silva, Goreti Lobarinhas, Isabel Palma, Jose P de Moura, Miguel T Rico, Quitéria Rato, Patrícia Pais, Susana Correia, Oana Moldovan, Maria J Virtuoso, Jose M Salgado, Ines Colaço, Andreea Dumitrescu, Calin Lengher, Svetlana Mosteoru, Alexey Meshkov, Alexandra Ershova, Tatiana Rozkova, Victoria Korneva, Kuznetsova T Yu, Vitaliy Zafiraki, Mikhail Voevoda, Victor Gurevich, Dmitry Duplyakov, Yulia Ragino, Maya Safarova, Igor Shaposhnik, Fahmi Alkaf, Alia Khudari, Nawal Rwaili, Faisal Al-Allaf, Mohammad Alghamdi, Mohammed A Batais, Turky H Almigbal, Abdulhalim Kinsara, Ashraf H A AlQudaimi, Zuhier Awan, Omer A Elamin, Hani Altaradi, Natasa Rajkovic, Ljiljana Popovic, Sandra Singh, Ljubica Stosic, Iva Rasulic, Nebojsa M Lalic, Carolyn Lam, Tan J Le, Eric L T Siang, Sanjaya Dissanayake, Justin T I-Shing, Tai E Shyong, Terrance C S Jin, Karin Balinth, Ingrid Buganova, Lubomira Fabryova, Michaela Kadurova, Alexander Klabnik, Miriam Kozárová, Jana Sirotiakova, Tadej Battelino, Jernej Kovac, Matej Mlinaric, Ursa Sustar, Katarina T Podkrajsek, Zlatko Fras, Borut Jug, Matija Cevc, Gillian J Pilcher, D J Blom, K H Wolmarans, B C Brice, Ovidio Muñiz-Grijalvo, Jose L Díaz-Díaz, Leopoldo P de Isla, Francisco Fuentes, Lina Badimon, François Martin, Angela Lux, Nien-Tzu Chang, Poranee Ganokroj, Mehmet Akbulut, Gökhan Alici, Fahri Bayram, Levent H Can, Ahmet Celik, Ceyhun Ceyhan, Fatma Y Coskun, Mesut Demir, Sabri Demircan, Volkan Dogan, Emre Durakoglugil, Ibrahim E Dural, Omer Gedikli, Aysa Hacioglu, Muge Ildizli, Salih Kilic, Bahadir Kirilmaz, Merih Kutlu, Aytekin Oguz, Oner Ozdogan, Ersel Onrat, Savas Ozer, Tevfik Sabuncu, Tayfun Sahin, Fatih Sivri, Alper Sonmez, Ahmet Temizhan, Selim Topcu, Abdullah Tuncez, Mirac Vural, Mustafa Yenercag, Dilek Yesilbursa, Zerrin Yigit, Aytul B Yildirim, Aylin Yildirir, Mehmet B Yilmaz, Bassam Atallah, Mahmoud Traina, Hani Sabbour, Dana A Hay, Neama Luqman, Abubaker Elfatih, Arshad Abdulrasheed, See Kwok, Nicolas D Oca, Ximena Reyes, Rano B Alieva, Ravshanbek D Kurbanov, Shavkat U Hoshimov, Ulugbek I Nizamov, Adolat V Ziyaeva, Guzal J Abdullaeva, Doan L Do, Mai N T Nguyen, Ngoc T Kim, Thanh T Le, Hong A Le, Lale Tokgozoglu, Alberico L Catapano, Kausik K RayEAS Familial Hypercholesterolaemia Studies Collaboration (FHSC): Mafalda Bourbon (INSA)Background: The European Atherosclerosis Society Familial Hypercholesterolaemia Studies Collaboration (FHSC) global registry provides a platform for the global surveillance of familial hypercholesterolaemia through harmonisation and pooling of multinational data. In this study, we aimed to characterise the adult population with heterozygous familial hypercholesterolaemia and described how it is detected and managed globally.
Methods: Using FHSC global registry data, we did a cross-sectional assessment of adults (aged 18 years or older) with a clinical or genetic diagnosis of probable or definite heterozygous familial hypercholesterolaemia at the time they were entered into the registries. Data were assessed overall and by WHO regions, sex, and index versus non-index cases.
Findings: Of the 61 612 individuals in the registry, 42 167 adults (21 999 [53·6%] women) from 56 countries were included in the study. Of these, 31 798 (75·4%) were diagnosed with the Dutch Lipid Clinic Network criteria, and 35 490 (84·2%) were from the WHO region of Europe. Median age of participants at entry in the registry was 46·2 years (IQR 34·3-58·0); median age at diagnosis of familial hypercholesterolaemia was 44·4 years (32·5-56·5), with 40·2% of participants younger than 40 years when diagnosed. Prevalence of cardiovascular risk factors increased progressively with age and varied by WHO region. Prevalence of coronary disease was 17·4% (2·1% for stroke and 5·2% for peripheral artery disease), increasing with concentrations of untreated LDL cholesterol, and was about two times lower in women than in men. Among patients receiving lipid-lowering medications, 16 803 (81·1%) were receiving statins and 3691 (21·2%) were on combination therapy, with greater use of more potent lipid-lowering medication in men than in women. Median LDL cholesterol was 5·43 mmol/L (IQR 4·32-6·72) among patients not taking lipid-lowering medications and 4·23 mmol/L (3·20-5·66) among those taking them. Among patients taking lipid-lowering medications, 2·7% had LDL cholesterol lower than 1·8 mmol/L; the use of combination therapy, particularly with three drugs and with proprotein convertase subtilisin-kexin type 9 inhibitors, was associated with a higher proportion and greater odds of having LDL cholesterol lower than 1·8 mmol/L. Compared with index cases, patients who were non-index cases were younger, with lower LDL cholesterol and lower prevalence of cardiovascular risk factors and cardiovascular diseases (all p<0·001).
Interpretation: Familial hypercholesterolaemia is diagnosed late. Guideline-recommended LDL cholesterol concentrations are infrequently achieved with single-drug therapy. Cardiovascular risk factors and presence of coronary disease were lower among non-index cases, who were diagnosed earlier. Earlier detection and greater use of combination therapies are required to reduce the global burden of familial hypercholesterolaemia.Pfizer, Amgen, Merck Sharp & Dohme, Sanofi-Aventis, Daiichi Sankyo, and Regeneron.info:eu-repo/semantics/publishedVersio
