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Combined PCSK9 and APOE Polymorphisms are Genetic Risk Factors Associated with Elevated Plasma Lipid Levels in a Thai Population

  • Original Article
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Lipids

Abstract

Proprotein convertase subtilisin/kexin type 9 (PCSK9) and apolipoprotein E (ApoE) play a key role in the regulation of lipid metabolism. We aimed to investigate the effects of PCSK9 (R46L, I474V, and E670G) and APOE polymorphisms on lipid levels in a Southern Thai population. A total of 495 participants (307 urban, 188 rural) were recruited for the study. Anthropometric and biochemical variables were evaluated. PCSK9 and APOE polymorphisms were analyzed using PCR–RFLP. The 46L urban male carriers had significantly higher diastolic blood pressure (DBP) and fasting blood sugar compared with non-carriers. In contrast, the 46L urban female carriers had significantly lower total cholesterol (TC) and LDL-C levels compared with non-carriers. The 474V rural female carriers had significantly lower HDL-C levels than non-carriers. The 670G urban female carriers showed significantly higher TC and LDL-C levels compared with non-carriers. APOE4 carriers had increased TC and LDL-C levels relative to APOE3 carriers in the urban males. APOE2 carriers had decreased TC and/or LDL-C levels compared with APOE3 carriers in urban males and females. A significant trend of increased TC and LDL-C levels was observed in non-APOE4-PCSK9 670EE carriers to APOE4-PCSK9 670EG carriers in urban subjects. In summary, R46L, I474V, and E670G may be genetic risk factors for cardiovascular disease (CVD) in urban males, rural females, and urban females, respectively. In contrast, R46L had a favorable lipid profiles that may protect against CVD in urban females. The combination of PCSK9 E670G and APOE polymorphisms may represent an independent factor for the determination of lipid levels.

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Abbreviations

APOE:

Apolipoprotein E

BMI:

Body mass index

CARDIA study:

Coronary artery risk development in young adults study

CVD:

Cardiovascular disease

DBP:

Diastolic blood pressure

DHS:

Dallas heart study

FBS:

Fasting blood sugar

GOF:

Gain-of-function

HDL-C:

High density lipoprotein cholesterol

LCAS:

Lipoprotein coronary atherosclerosis study

LDL-C:

Low density lipoprotein cholesterol

LDLR:

Low density lipoprotein receptor

LOF:

Loss-of-function

PCR-RFLP:

Polymerase chain reaction and restriction fragment length polymorphism

PCSK9:

Proprotein convertase subtilisin/kexin type 9

PLIC study:

Progression of lesions in the intima of the carotid study

PROSPER:

Prospective study of pravastatin in the elderly at risk

TC:

Total cholesterol

TG:

Triglyceride

UK:

United Kingdom

UV:

Ultraviolet

WC:

Waist circumference

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Acknowledgments

This work was supported by Grants from the Office of the Higher Education Commission, the Thailand Research Fund, and Walailak University (Project No. MRG5580068). The authors would like to thank to all subjects who participated in this study.

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Authors and Affiliations

  1. School of Allied Health Sciences and Public Health, Walailak University, 222 Thaiburi, Thasala, Nakhon Si Thammarat, 80161, Thailand

    Nutjaree Jeenduang & Smith Wanmasae

  2. Department of Clinical Chemistry, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand

    Sureerut Porntadavity

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  1. Nutjaree Jeenduang
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  3. Smith Wanmasae
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Correspondence to Nutjaree Jeenduang.

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Jeenduang, N., Porntadavity, S. & Wanmasae, S. Combined PCSK9 and APOE Polymorphisms are Genetic Risk Factors Associated with Elevated Plasma Lipid Levels in a Thai Population. Lipids 50, 543–553 (2015). https://doi.org/10.1007/s11745-015-4017-9

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