ABCMdb

PMID: 20797885

Guevara-Cruz M, Tovar AR, Larrieta E, Canizales-Quinteros S, Torres N
Increase in HDL-C concentration by a dietary portfolio with soy protein and soluble fiber is associated with the presence of the ABCA1R230C variant in hyperlipidemic Mexican subjects.
Mol Genet Metab. 2010 Oct-Nov;101(2-3):268-72. Epub 2010 Aug 10., [PubMed]

Sentences

No. Mutations Sentence Comment

2 ABCA1 p.Arg230Cys Low plasma high-density lipoprotein cholesterol (HDL-C) levels are the most common dyslipidemia in Mexican adults and are coupled with the presence of the ABCA1 R230C genotype. Login to comment 3 ABCA1 p.Arg219Lys Therefore, the aim of this study was to assess the response of HDL-C concentration to a dietary portfolio in a group of Mexican hyperlipidemic subjects with ABCA1R230C (rs9282541) and R219K (rs2230806) polymorphisms. Login to comment 6 ABCA1 p.Arg230Cys Results: Hyperlipidemic subjects with the ABCA1 R230C genotype showed lower HDL-C concentrations at the beginning of the study and were better responders to the dietary treatment than subjects with the ABCA1 R230R genotype (+4.6% vs. +14.6%) (p=.05). Login to comment 7 ABCA1 p.Arg230Cys According to gender and the presence of the R230C genotype, women responded more significantly to the dietary treatment, reflected by an increase of 21.9% in HDL concentration (p=.022), than women with R230R genotype who only experienced an increase of 2.7% in HDL-C concentration. Login to comment 8 ABCA1 p.Arg219Lys There was no association between the presence of the ABCA1 R219K variant (p=.544) and HDL concentration. Login to comment 9 ABCA1 p.Arg230Cys Conclusion: Hyperlipidemic Mexican subjects with the ABCA1 R230C genotype showed lower HDL- concentrations and were better responders to dietary portfolio treatments for increasing HDL-C concentrations than subjects with the R230R genotype. Login to comment 18 ABCA1 p.Arg230Cys A frequent cholesterol transporter ABCA1 gene variant (R230C) apparently exclusive to Native American individuals was associated with low HDL-C levels [2], obesity and type 2 diabetes in Mexican Mestizos. Login to comment 31 ABCA1 p.Arg219Lys The effect of ABCA1 genetic polymorphisms on HDL-C levels has been widely documented mainly in adults [9]; specifically, the K allele of the ABCA1 R219K polymorphism has been associated with increased HDL-concentrations [10-13] and a reduced incidence of coronary heart disease (CHD) events [10,11]. Login to comment 32 ABCA1 p.Arg230Cys The high frequency of the ABCA1 R230C variant in the Mexican population has been suggested as a selective advantage. Login to comment 33 ABCA1 p.Arg230Cys Thus, those individuals with the R230C variant probably had a selective advantage during periods of famine. Login to comment 34 ABCA1 p.Arg230Cys However, R230C carriers currently exposed to an obesogenic environment may be prone to the development of diseases grouped under the metabolic syndrome. Login to comment 35 ABCA1 p.Arg230Cys The thrifty genotype may predispose our population to respond in a different way to changes in lifestyle, including changes in diet, which would imply the need to establish strategies to treat dyslipidemias in subjects who are carriers of R230C variant compared with individuals homozygous for the wild type variant R230R. Login to comment 36 ABCA1 p.Arg219Lys ABCA1 p.Arg230Cys Therefore, the aim of this study was to assess the response of HDL-cholesterol concentration to a dietary portfolio consisting of soy protein and soluble fiber in a group of Mexican hyperlipidemic subjects with or without ABCA1(R230C, rs9282541) and R219K (rs2230806) polymorphisms and to evaluate its association with the dietary portfolio in responders and non-responders. Login to comment 62 ABCA1 p.Arg219Lys ABCA1 p.Arg230Cys [22] These two single-nucleotide polymorphisms (SNPs) of the gene ABCA1 (R230C variant (rs9282541) and R219K (rs2230806)) were determined using polymerase chain reaction (PCR)-based TaqMan allele discrimination assays (ABI Prism 7900HT Sequence Detection System; Applied Biosystems, Foster City, CA) [26]. Login to comment 70 ABCA1 p.Arg219Lys ABCA1 p.Arg230Cys Results Genotype distribution (wild type allele homozygote, variant heterozygote, variant homozygote) for each polymorphism was as follows: R230C (31, 12, 0) and R219K (19, 21, 3). Login to comment 71 ABCA1 p.Arg219Lys ABCA1 p.Arg230Cys Allele frequencies (wild-type, variant) were for R230C (75.5%, 24.4%) and R219K (68.6%, 31.4%). Login to comment 73 ABCA1 p.Arg230Cys ABCA1 p.Arg230Cys ABCA1 R230C Hyperlipidemic subjects with the ABCA1 R230C variant produced an HDL-C percentage change between basal and final concentration significantly higher after the consumption of the dietary treatment (p=.05) than subjects with the R230R genotype, Table 1. Login to comment 74 ABCA1 p.Arg230Cys Interestingly, subjects with the R230C genotype showed lower basal HDL-C concentrations (36.8±1.3) than subjects with the R230 R (39.9±1.5) genotype. Login to comment 75 ABCA1 p.Arg230Cys Hyperlipidemic subjects with the ABCA1 R230C genotype were better responders to the low saturated fat diet with respect to HDL-C (5% increase) than the wild type genotype subjects (0.65% increase). Login to comment 78 ABCA1 p.Arg230Cys ABCA1 p.Arg230Cys The percent change in HDL-C concentration in the wild type genotype after the dietary treatment was +4.6±2.3%, whereas in subjects with the R230C genotype was +14.6% (p=.05) (Fig. 1). Login to comment 79 ABCA1 p.Arg230Cys According to gender and the presence of the R230C genotype, women responded more significantly to the dietary treatment, reflected by an increase of 21.9% in HDL concentration (p=.022), than women with the R230R genotype who only experienced an increase of 2.7% in HDL-C concentration (Fig. 2). Login to comment 80 ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys ABCA1 R219K was also studied due to its association with the fenofibrate response; however, there was no association between the presence of the ABCA1 R219K variant and the percentage of change in HDL concentration after the dietary treatment with soy protein and soluble fiber (p=.544) (Fig. 3). Login to comment 87 ABCA1 p.Arg230Cys The ABCA1 R230C variant is apparently exclusive to Native American individuals and is associated with low HDL-C concentrations [2], obesity [24] and type 2 diabetes in Mexican Mestizos [25]. Login to comment 88 ABCA1 p.Arg230Cys In view of the high frequency of this variant (12%) in Native American populations [2], hyperlipidemic subjects in this study were evaluated with respect to the presence of the ABCA1 R230C variant. Login to comment 89 ABCA1 p.Arg230Cys Interestingly, hyper-responders to the low saturated fat diet and the dietary portfolio with respect to HDL concentrations were subjects who Table 1 Serum lipids in hyperlipidemic subjects after 1 month with LSF diet and after 1 or 2 months of LSF diet and 25 g of soy protein and 15 g of soluble fiber (SSF) according to the ABCA1 R230C. Login to comment 90 ABCA1 p.Arg230Cys ABCA1 p.Arg230Cys ABCA1 p.Arg230Cys ABCA1 p.Arg230Cys ABCA1 p.Arg230Cys ABCA1 p.Arg230Cys ABCA1 p.Arg230Cys ABCA1 p.Arg230Cys BASAL 1st month LSFD 2nd month LSFD+SSF 3rd month LSF+SSF Percentage of change after 3 months of treatment p Total colesterol (mg/dl) R230R 281.4±8.4a 260.3±8.2 b 226.5±6.4 c 222.0±6.2 c -20.2±2.0 .69 R230C 287.8±16.9 a 275.1±19.9 a,b 248.5±15.9 a,b 232.5±13.8 b -18.7±2.8 Triglycerides (mg/dl) R230R 303.6±16.4 a 284.7±21.9 a 159.5±10.8 b 171.0±10.9 b -39.61;4.3 .41 R230C 288.5±23.4 a 298.3±33.2 a 187.6±21.7 b 198.0±27.1 b -32.8±6.9 HDL Cholesterol (mg/dl) R230R 39.9±1.5 39.9±11.4 40.8±1.4 41.3±1.4 +4.6±2.3 .05 R230C 36.8±1.3 38.8±1.9 39.2±1.9 42.1±2.6 +14.6±5.6 LDL Cholesterol (mg/dl) R230R 180.7±9.6 a 163.4±10.4 a,b 153.7±7.4 b 146.4±7.9 b -17.5±3.3 .46 R230C 193.2±16.9 176.7±21.1 171.7±18.0 150.7±16.2 -22.1±5.3 Values are mean±SEM. Differences between the basal and final parameters were evaluated by one-way ANOVA and differences between genotypes and percentage change after treatment were tested with an independent sample Student's t-test. Login to comment 94 ABCA1 p.Arg230Cys Change from baseline in plasma HDL-cholesterol concentration in 43 hyperlipidemic participants divided according to ABCA-1 R230R or R230C genotypes who underwent 1 month of low saturated fat dietary (LSF) treatment, followed by 2 months of LSF with the addition of 25 g of soy protein and 15 g of soluble fiber. Login to comment 96 ABCA1 p.Arg230Cys The p=0.05 value indicates the difference between percentage of change in HDL-C concentration after 3 months of dietary treatment in subjects with R230C genotype. Login to comment 98 ABCA1 p.Arg230Cys Change from baseline in plasma HDL-cholesterol concentration in 23 hyperlipidemic women divided according to ABCA-1 R230R or R230C genotypes who underwent one month of low saturated fat dietary (LSF) treatment, followed by 2 months of LSF with the addition of 25 g of soy protein and 15 g of soluble fiber. Login to comment 99 ABCA1 p.Arg230Cys The p=0.02 value indicates the difference between percentage of change in HDL-C concentration after 3 month of dietary treatment in subjects with R230C genotype. Login to comment 100 ABCA1 p.Arg230Cys presented the ABCA1 R230C genotype. Login to comment 101 ABCA1 p.Arg230Cys As can be seen in Fig. 1, subjects with the ABCA1 R230C genotype showed lower HDL- concentrations at the beginning of the study and were better responders to dietary treatments than subjects with the R230R genotype. Login to comment 102 ABCA1 p.Arg230Cys It has been reported that pharmacological treatment with fenofibrate increased HDL-C by 10% in 228 hyperlipidemic subjects [26], whereas dietary treatment with this specific dietary portfolio increased HDL-C concentration by 14.6% in the 43 patients with hyperlipidemia and 22% in women with the R230C genotype. Login to comment 104 ABCA1 p.Arg230Cys The possible mechanism by which soy protein increases HDL-C concentration in R230C carriers is not clear. Login to comment 112 ABCA1 p.Arg230Cys In Mexico, approximately 3.7 million adults with low HDL-C concentrations and the ABCA1 R230C variant can benefit from the consumption of a specific dietary portfolio. Login to comment