Perla Graciela Rodríguez-Gutiérrez , Teresita de Jesús Hernández-Flores , Paola Montserrat Zepeda-Olmos , Christian Daniel Reyes-Rodríguez , Kiabeth Robles-Espinoza , Ulises Solís-Gómez , Juan Ramón González-García , María Teresa Magaña-Torres
{"title":"墨西哥瓦哈卡社区因 LDLR c.2271del 变异的创始人效应而导致家族性高胆固醇血症的高患病率","authors":"Perla Graciela Rodríguez-Gutiérrez , Teresita de Jesús Hernández-Flores , Paola Montserrat Zepeda-Olmos , Christian Daniel Reyes-Rodríguez , Kiabeth Robles-Espinoza , Ulises Solís-Gómez , Juan Ramón González-García , María Teresa Magaña-Torres","doi":"10.1016/j.arcmed.2024.102971","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><p>In Mexico, familial hypercholesterolemia (FH) is underdiagnosed, but population screening in small communities where at least one homozygous patient has already been detected results in a useful and inexpensive approach to reduce this problem. Considering that we previously reported nine homozygous cases from the state of Oaxaca, we decided to perform a population screening to identify patients with FH and to describe both their biochemical and genetic characteristics.</p></div><div><h3>Methods</h3><p>LDL cholesterol (LDLc) was quantified in 2,093 individuals from 11 communities in Oaxaca; either adults with LDLc levels ≥170 mg/dL or children with LDLc ≥130 mg/dL were classified as suggestive of FH and therefore included in the genetic study. <em>LDLR</em> and <em>APOB</em> (547bp fragment of exon 26) genes were screened by sequencing and MLPA analysis.</p></div><div><h3>Results</h3><p>Two hundred and five individuals had suggestive FH, with a mean LDLc of 223 ± 54 mg/dL (range: 131–383 mg/dL). Two pathogenic variants in the <em>LDLR</em> gene were detected in 149 individuals: c.-139_-130del (<em>n</em> = 1) and c.2271del (<em>n</em> = 148). All patients had a heterozygous genotype. With the cascade screening of their relatives (<em>n</em> = 177), 15 heterozygous individuals for the c.2271del variant were identified, presenting a mean LDLc of 133 ± 35 mg/dL (range: 60–168 mg/dL).</p></div><div><h3>Conclusions</h3><p>The FH frequency in this study was 7.8% (164/2093), the highest reported worldwide. A founder effect combined with inbreeding could be responsible for the high percentage of patients with the <em>LDLR</em> c.2271del variant (99.4%), which allowed us to detect both significant biochemical heterogeneity and incomplete penetrance; hence, we assumed the presence of phenotype-modifying variants.</p></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":null,"pages":null},"PeriodicalIF":4.7000,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"High Prevalence of Familial Hypercholesterolemia Due to the Founder Effect of the LDLR c.2271del Variant in Communities of Oaxaca, Mexico\",\"authors\":\"Perla Graciela Rodríguez-Gutiérrez , Teresita de Jesús Hernández-Flores , Paola Montserrat Zepeda-Olmos , Christian Daniel Reyes-Rodríguez , Kiabeth Robles-Espinoza , Ulises Solís-Gómez , Juan Ramón González-García , María Teresa Magaña-Torres\",\"doi\":\"10.1016/j.arcmed.2024.102971\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Introduction</h3><p>In Mexico, familial hypercholesterolemia (FH) is underdiagnosed, but population screening in small communities where at least one homozygous patient has already been detected results in a useful and inexpensive approach to reduce this problem. Considering that we previously reported nine homozygous cases from the state of Oaxaca, we decided to perform a population screening to identify patients with FH and to describe both their biochemical and genetic characteristics.</p></div><div><h3>Methods</h3><p>LDL cholesterol (LDLc) was quantified in 2,093 individuals from 11 communities in Oaxaca; either adults with LDLc levels ≥170 mg/dL or children with LDLc ≥130 mg/dL were classified as suggestive of FH and therefore included in the genetic study. <em>LDLR</em> and <em>APOB</em> (547bp fragment of exon 26) genes were screened by sequencing and MLPA analysis.</p></div><div><h3>Results</h3><p>Two hundred and five individuals had suggestive FH, with a mean LDLc of 223 ± 54 mg/dL (range: 131–383 mg/dL). Two pathogenic variants in the <em>LDLR</em> gene were detected in 149 individuals: c.-139_-130del (<em>n</em> = 1) and c.2271del (<em>n</em> = 148). All patients had a heterozygous genotype. With the cascade screening of their relatives (<em>n</em> = 177), 15 heterozygous individuals for the c.2271del variant were identified, presenting a mean LDLc of 133 ± 35 mg/dL (range: 60–168 mg/dL).</p></div><div><h3>Conclusions</h3><p>The FH frequency in this study was 7.8% (164/2093), the highest reported worldwide. A founder effect combined with inbreeding could be responsible for the high percentage of patients with the <em>LDLR</em> c.2271del variant (99.4%), which allowed us to detect both significant biochemical heterogeneity and incomplete penetrance; hence, we assumed the presence of phenotype-modifying variants.</p></div>\",\"PeriodicalId\":8318,\"journal\":{\"name\":\"Archives of Medical Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.7000,\"publicationDate\":\"2024-03-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Archives of Medical Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0188440924000249\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archives of Medical Research","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0188440924000249","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
High Prevalence of Familial Hypercholesterolemia Due to the Founder Effect of the LDLR c.2271del Variant in Communities of Oaxaca, Mexico
Introduction
In Mexico, familial hypercholesterolemia (FH) is underdiagnosed, but population screening in small communities where at least one homozygous patient has already been detected results in a useful and inexpensive approach to reduce this problem. Considering that we previously reported nine homozygous cases from the state of Oaxaca, we decided to perform a population screening to identify patients with FH and to describe both their biochemical and genetic characteristics.
Methods
LDL cholesterol (LDLc) was quantified in 2,093 individuals from 11 communities in Oaxaca; either adults with LDLc levels ≥170 mg/dL or children with LDLc ≥130 mg/dL were classified as suggestive of FH and therefore included in the genetic study. LDLR and APOB (547bp fragment of exon 26) genes were screened by sequencing and MLPA analysis.
Results
Two hundred and five individuals had suggestive FH, with a mean LDLc of 223 ± 54 mg/dL (range: 131–383 mg/dL). Two pathogenic variants in the LDLR gene were detected in 149 individuals: c.-139_-130del (n = 1) and c.2271del (n = 148). All patients had a heterozygous genotype. With the cascade screening of their relatives (n = 177), 15 heterozygous individuals for the c.2271del variant were identified, presenting a mean LDLc of 133 ± 35 mg/dL (range: 60–168 mg/dL).
Conclusions
The FH frequency in this study was 7.8% (164/2093), the highest reported worldwide. A founder effect combined with inbreeding could be responsible for the high percentage of patients with the LDLR c.2271del variant (99.4%), which allowed us to detect both significant biochemical heterogeneity and incomplete penetrance; hence, we assumed the presence of phenotype-modifying variants.
期刊介绍:
Archives of Medical Research serves as a platform for publishing original peer-reviewed medical research, aiming to bridge gaps created by medical specialization. The journal covers three main categories - biomedical, clinical, and epidemiological contributions, along with review articles and preliminary communications. With an international scope, it presents the study of diseases from diverse perspectives, offering the medical community original investigations ranging from molecular biology to clinical epidemiology in a single publication.