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Prevalent Variants in the LDLR Gene Impair Responsiveness to Rosuvastatin among Family Members of Patients with Premature Myocardial Infarction.
Kien, Nguyen Trung; Nghia, Tran Tin; Hoang, Nguyen Minh; Phu, Tran Nguyen Trong; Nga, Pham Thi Ngoc; Mai, Ha Thi Thao; Espinoza, J Luis.
Afiliación
  • Kien NT; Faculty of Medicine, Can Tho University of Medicine and Pharmacy, Can Tho 900000, Vietnam.
  • Nghia TT; Faculty of Medicine, Can Tho University of Medicine and Pharmacy, Can Tho 900000, Vietnam.
  • Hoang NM; Tra Vinh General Hospital, Tra Vinh 940000, Vietnam.
  • Phu TNT; Faculty of Medicine, Can Tho University of Medicine and Pharmacy, Can Tho 900000, Vietnam.
  • Nga PTN; Faculty of Medicine, Chulalongkorn University, 1873, Rama 4 Road, Pathumwan, Bangkok 10330, Thailand.
  • Mai HTT; Faculty of Medicine, Can Tho University of Medicine and Pharmacy, Can Tho 900000, Vietnam.
  • Espinoza JL; Faculty of Medicine, Can Tho University of Medicine and Pharmacy, Can Tho 900000, Vietnam.
J Pers Med ; 13(12)2023 Dec 18.
Article en En | MEDLINE | ID: mdl-38138952
ABSTRACT

BACKGROUND:

Familial hypercholesterolemia (FH) is an inherited metabolic disorder characterized by high levels of low-density lipoprotein cholesterol (LDL-c) from birth. About 85% of all FH cases are caused by pathogenic variants in the LDLR gene. Individuals with FH have increased cardiovascular risk, including a high risk of premature myocardial infarction (PMI).

METHODS:

We conducted an opportunistic exome screening to identify variants in the LDLR gene among Vietnamese patients with PMI treated at a general hospital in southern Vietnam. A cascade testing for LDLR variants was conducted in their relatives within three generations, and the effects of the LDLR variant on the response to rosuvastatin treatment were also studied using a comparative before-and-after study design on those who were eligible.

RESULTS:

A total of 99 participants from the three generations of four PMI patients were recruited, mean age 37.3 ± 18.5 years, 56.6% males. Sanger sequencing revealed two variants in the LDLR gene variant rs577934998 (c.664T>C), detected in 17 individuals within one family, and variant rs12710260 (c.1060+10G>C), found in 32 individuals (49.5%) in the other three families tested. Individuals harboring the variant c.664T>C had significantly higher baseline LDL-c and total cholesterol levels compared to those with variant c.1060+10G>C (classified as benign) or those without LDLR variants, and among the 47 patients subjected to a 3-month course of rosuvastatin therapy, those with variant c.664T>C had a significantly higher risk of not achieving the LDL-c target after the course of treatment compared to the c.1060+10G>C carriers.

CONCLUSIONS:

These findings provide evidence supporting the existence of pathogenic LDLR variants in Vietnamese patients with PMI and their relatives and may indicate the need for personalizing lipid-lowering therapies. Further studies are needed to delineate the extent and severity of the problem.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Pers Med Año: 2023 Tipo del documento: Article País de afiliación: Vietnam Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Pers Med Año: 2023 Tipo del documento: Article País de afiliación: Vietnam Pais de publicación: Suiza