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

IF 4.7 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Archives of Medical Research Pub Date : 2024-03-20 DOI:10.1016/j.arcmed.2024.102971
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
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引用次数: 0

摘要

导言:在墨西哥,家族性高胆固醇血症(FH)的诊断率很低,但在已经发现至少有一名同基因患者的小社区进行人群筛查,是减少这一问题的有效而廉价的方法。考虑到我们以前曾报告过瓦哈卡州的 9 例同源病例,我们决定进行一次人群筛查,以确定 FH 患者,并描述他们的生化和遗传特征。方法 对来自瓦哈卡州 11 个社区的 2093 人进行了低密度脂蛋白胆固醇(LDLc)定量分析;将低密度脂蛋白胆固醇水平≥170 毫克/分升的成人或低密度脂蛋白胆固醇水平≥130 毫克/分升的儿童归类为提示 FH 患者,并因此纳入遗传研究。通过测序和 MLPA 分析筛选了 LDLR 和 APOB(外显子 26 的 547bp 片段)基因。在 149 例患者中检测到两个 LDLR 基因致病变异:c.-139_-130del(1 例)和 c.2271del(148 例)。所有患者均为杂合基因型。结论本研究中的 FH 频率为 7.8%(164/2093),是全球报告的最高频率。创始人效应与近亲繁殖相结合可能是导致高比例的 LDLR c.2271del 变体患者(99.4%)的原因,这使我们能够检测到显著的生化异质性和不完全渗透性;因此,我们假定存在表型改变变体。
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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.

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来源期刊
Archives of Medical Research
Archives of Medical Research 医学-医学:研究与实验
CiteScore
12.50
自引率
0.00%
发文量
84
审稿时长
28 days
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.
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