J Med Assoc Thai Vol. 99 No. 6 2016 723 J Med Assoc Thai 2016; 99 (6): 723-31 Full text. e-Journal: http://www.jmatonline.com Correspondence to: Kriengsinyos W, Institute of Nutrition, Mahidol University, 999 Phutthamonthon 4 Road, Salaya, Phutthamonthon, Nakhon Pathom 73170, Thailand. Phone: +66-2-28002380 ext. 415, Fax: +66-2-4419344 E-mail: wantanee.krieng@mahidol.ac.th Impact of Genetic Polymorphism on LDL-C Response to Plant Stanol Ester Intake Chaowanee Chupeerach PhD*, Uthaiwan Suttisansanee PhD*, Nattira On-Nom PhD*, Wantanee Kriengsinyos PhD* * Institute of Nutrition, Mahidol University, Salaya, Nakhon Pathom, Thailand Background: The high blood cholesterol level could be prevented by plant stanol ester (Staest) consumption. In addition, the genetic polymorphism of cholesterol transporters might be related with lipid profile and subsequently response to Staest intake. Objective: To investigate the effect of single nucleotide polymorphism in ATP-binding cassette hetero-dimeric G5/G8 (ABCG5/G8) and Niemann-Pick C1 Like1 protein (NPC1L1) gene on LDL-C response subsequent to plant Staest intake in Thai Subjects. Material and Method: The blood samples were collected from 113 subjects for genotyping. The single nucleotide polymorphisms (SNPs) of ABCG5/G8 positions; rs6720173 (Q604E), rs4148211 (C54Y), rs4148217 (T400K), rs3806471 (5’UTR-145), and NPC1L1; positon; rs2072183 (L272L) were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: After Staest intake, the subjects with QE genotype (Q604E of ABCG5) showed a 4-fold significant decrease in LDL-C level (14.17±10.67%) compared to subjects with QQ genotype (3.50±10.65%) (p = 0.003). Moreover, the pronounced effect of Q604E polymorphism was observed in subjects after intake of Staest with meal. However, no significant difference in these markers was observed in subjects carrying other mutations. Conclusion: Thus, it could be suggested that non-synonymous gene polymorphism resulted substitution of uncharged glutamine (Q) with negatively charged glutamic acid (E) at position 604, thereby possibly alter the function of transporter proteins. Besides, the genetic variation in these genes might be related with serum lipid profiles. Moreover, Q604E mutation of ABCG5 in each individual with meal effect could lead to particular response towards LDL-C level after Staest intervention. Keywords: ABCG5/G8, Single nucleotide polymorphism, Plant stanol ester, Nutrigenetic, Thai subject Cardiovascular disease (CVD) is the most common cause of death and public health concern worldwide (1) . An important risk factor in CVD pathogenesis is hypercholesteroemia or dyslipidemia status, especially low-density lipoprotein cholesterol (LDL-C) condition. The major causes of hyper- cholesterolemia, a conspicuous pre symptom of CVD are hypothesized to be genetic and lifestyle factors. The former involves genetic polymorphism, while the later includes dietary pattern or physical activity (2) . Nowadays, medicinal treatments using synthetic drugs such as statins with lowering serum cholesterol effect are commonly used by most CVD patients. Nevertheless, these drugs produce adverse effects such as nausea, diarrhea, and constipation in CVD patients. The usage dose of these drugs varies from person to person, thereby making CVD treatment more specific to each individual. Thus, green medicines (natural products) that could decrease serum cholesterol level have become a target strategy for CVD prevention. Moreover, it was previously reported that cholesterol absorption in human, especially LDL-C level, could be decreased via competition of cholesterol influx mechanism after consumption of some functional foods or medicinal plants (3) . The difference in effective response against cholesterol level after treatment or consumption of food such as dietary plant stanol ester (Staest) was observed (4,5) . This inter-individual response towards cholesterol absorption had been hypothesized as the effect of genetic variation in intestinal cholesterol transportation (6) . Several studies had reported the relationship between genetic variation (resulting in mutation in transporter protein) and regulation of sterol transportation via small intestine and other organs in vivo (7,8) . Two major transporter proteins including hetero-dimeric ATP-binding cassette (G5 and G8 or