ABCMdb

PMID: 22190032

Romero-Hidalgo S, Villarreal-Molina T, Gonzalez-Barrios JA, Canizales-Quinteros S, Rodriguez-Arellano ME, Yanez-Velazco LB, Bernal-Alcantara DA, Villa AR, Antuna-Puente B, Acuna-Alonzo V, Merino-Garcia JL, Moreno-Sandoval HN, Carnevale A
Carbohydrate intake modulates the effect of the ABCA1-R230C variant on HDL cholesterol concentrations in premenopausal women.
J Nutr. 2012 Feb;142(2):278-83. Epub 2011 Dec 21., [PubMed]

Sentences

No. Mutations Sentence Comment

1 ABCA1 p.Arg230Cys ABCA1 p.Arg230Cys Adolfo Lo´pez Mateos", and 8 Medical Direction, Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, Mexico City, Mexico; 9 School of Chemistry, and 10 Department of Public Health, School of Medicine, Universidad Nacional Auto´noma de Me´xico, Mexico City, Mexico; 11 Unit of Molecular Biology and Genomic Medicine, Instituto Nacional de Ciencias Me´dicas y Nutricio´n Salvador Zubira´n, Mexico City, Mexico; 12 Department of Research in Biochemistry, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico; and 13 Molecular Genetics Laboratory, Escuela Nacional de Antropologı´a e Historia, Mexico City, Mexico Abstract The R230C variant of the ATP-binding cassette transporter A1 (ABCA1) gene has been consistently associated with decreased HDL-cholesterol (HDL-C) concentrations in several studies in the Mexican mestizo population. Login to comment 2 ABCA1 p.Arg230Cys However, information on how diet composition modifies the effect of the ABCA1-R230C variant on HDL-C concentrations is very scarce. Login to comment 3 ABCA1 p.Arg230Cys The aim of the present study was to analyze whether the effect of ABCA1-R230C on HDL-C concentrations is modulated by dietary factors in a nationwide population sample of 3591 adults from the National Health and Nutrition Survey conducted by the State`s Employees` Social Security and Social Services Institute. Login to comment 4 ABCA1 p.Arg230Cys All participants answered a validated questionnaire to assess health status and weekly food consumption. Fasting blood samples were drawn for biochemical analysis and DNA extraction, and the ABCA1-R230C variant was genotyped using TaqMan assays. Login to comment 7 ABCA1 p.Arg230Cys A significant negative correlation between carbohydrate consumption and HDL-C concentrations was observed in women bearing the R230C variant (P = 0.021) and a significant gene-diet interaction was found only in premenopausal women (P = 0.037). Login to comment 8 ABCA1 p.Arg230Cys In conclusion, the effect of the ABCA1-R230C gene variant on HDL-C concentrations is modulated by carbohydrate intake in premenopausal women. Login to comment 9 ABCA1 p.Arg230Cys This finding may help design optimized dietary interventions according to sex and ABCA1-R230C genotype. Login to comment 14 ABCA1 p.Arg230Cys The R230C-ABCA1 gene variant was recently found to be private to the Americas and strongly associated with low HDL-C in Mexican mestizos and Native American populations (19-23). Login to comment 34 ABCA1 p.Arg230Cys However, information on how diet composition modifies the effect of the ABCA1-R230C variant on HDL-C concentrations is very scarce. Login to comment 35 ABCA1 p.Arg230Cys To date, there is only one report where hyperlipidemic individuals carrying the R230C risk allele showed a better HDL-C concentration response to a specific dietary intervention (low-saturated fat diet plus 25 g soy protein and 15 g soluble fiber) (28). Login to comment 36 ABCA1 p.Arg230Cys ABCA1 p.Arg230Cys The purpose of the present study was to analyze whether specific diet components modulate the effect of the ABCA1-R230C variant on HDL-C plasma concentrations to provide the bases for optimized dietary interventions. Login to comment 37 ABCA1 p.Arg230Cys To date, there is only one report where hyperlipidemic individuals carrying the R230C risk allele showed a better HDL-C concentration response to a specific dietary intervention (low-saturated fat diet plus 25 g soy protein and 15 g soluble fiber) (28). Login to comment 38 ABCA1 p.Arg230Cys The purpose of the present study was to analyze whether specific diet components modulate the effect of the ABCA1-R230C variant on HDL-C plasma concentrations to provide the bases for optimized dietary interventions. Login to comment 58 ABCA1 p.Arg230Cys The R230C variant (rs9282541) was genotyped using TaqMan assays (ABI Prism 7900HT Sequence Detection System, Applied Biosystems). Login to comment 60 ABCA1 p.Arg230Cys The R230C variant (rs9282541) was genotyped using TaqMan assays (ABI Prism 7900HT Sequence Detection System, Applied Biosystems). Login to comment 66 ABCA1 p.Arg230Cys ANCOVA was used to determine associations between the R230C variant and metabolic variables, adjusting for age, BMI, smoking, and alcohol consumption. Login to comment 67 ABCA1 p.Arg230Cys Simple linear regression models were built to study the effect of diet components on HDL-C concentrations stratified by sex and genotype, and multiple linear regression models were used to assess the interaction between the proportion of dietary carbohydrates and the R230C polymorphism on HDL-C concentrations, adjusting for the variables mentioned above. Login to comment 68 ABCA1 p.Arg230Cys ANCOVA was used to determine associations between the R230C variant and metabolic variables, adjusting for age, BMI, smoking, and alcohol consumption. Login to comment 69 ABCA1 p.Arg230Cys Simple linear regression models were built to study the effect of diet components on HDL-C concentrations stratified by sex and genotype, and multiple linear regression models were used to assess the interaction between the proportion of dietary carbohydrates and the R230C polymorphism on HDL-C concentrations, adjusting for the variables mentioned above. Login to comment 72 ABCA1 p.Arg230Cys The C risk allele frequency was 9.3% in the TABLE 1 Anthropometric and serum biochemical measurements, lifestyle characteristics, and genotype distribution of the study participants stratified by sex1 Men (n = 1160) Women2 (n = 2431) Age, y 48.3 6 14.2 45.9 6 12.5b Anthropometric variables BMI, kg/m2 28.5 6 4.3 28.3 6 5.1 Weight, kg 80.1 6 15.0 68.7 6 14.0b Height, cm 167.6 6 7.6 155.8 6 6.9b Waist, cm 98.6 6 11.5 91.2 6 13.2b Metabolic variables Total-C, mmol/L 5.5 6 1.3 5.4 6 1.1 HDL-C, mmol/L 1.0 6 0.2 1.2 6 0.4b LDL-C, mmol/L 3.4 6 0.9 3.4 6 0.9 TG, mmol/L 2.8 6 3.0 1.9 6 1.3b Glucose, mmol/L 61.2 6 26.3 56.3 6 20.9b Systolic blood pressure, mm Hg 130.3 6 16.1 122.2 6 16.5b Diastolic blood pressure, mm Hg 81.9 6 10.3 77.3 6 10.6b Dietary intake Total energy, kcal/d 2660 6 913 2220 6 804b Proteins, % energy 13.5 6 3.2 14.2 6 3.3b Proteins, g/d 87.9 6 31.1 77.3 6 28.8b Carbohydrates, % energy 55.3 6 9.3 57.6 6 8.3b Carbohydrates, g/d 363 6 126 318 6 122b Fats, % energy 28.4 6 6.3 29.4 6 6.3b Fats, g/d 84.2 6 34.7 73.2 6 33.3b Other characteristics Alcohol consumers, n (%) 986 (85.2) 1294 (53.5)b Daily, n (%) 23 (2.3) 10 (0.8) Weekly, n (%) 270 (27.4) 102 (7.9) Monthly, n (%) 122 (12.4) 82 (6.3) Occasionally, n (%) 571 (57.9) 1100 (85.0) Physical activity, h/wk 6.0 6 10.7 5.6 6 9.8 Daily smokers, n (%) 276 (23.8) 330 (13.6)b Overweight, n (%) 536 (46.7) 996 (41.6)a Obesity, n (%) 362 (31.5) 731 (30.6) ABCA1-R230C variant, n (%) RR 949 (81.8) 2010 (82.7) RC 202 (17.4) 398 (16.4) CC 9 (0.8) 23 (0.9) 1 Values are expressed as mean 6 SD or n (%). Login to comment 74 ABCA1 p.Arg230Cys The C risk allele frequency was 9.3% in the TABLE 1 Anthropometric and serum biochemical measurements, lifestyle characteristics, and genotype distribution of the study participants stratified by sex1 Men (n = 1160) Women2 (n = 2431) Age, y 48.3 6 14.2 45.9 6 12.5b Anthropometric variables BMI, kg/m2 28.5 6 4.3 28.3 6 5.1 Weight, kg 80.1 6 15.0 68.7 6 14.0b Height, cm 167.6 6 7.6 155.8 6 6.9b Waist, cm 98.6 6 11.5 91.2 6 13.2b Metabolic variables Total-C, mmol/L 5.5 6 1.3 5.4 6 1.1 HDL-C, mmol/L 1.0 6 0.2 1.2 6 0.4b LDL-C, mmol/L 3.4 6 0.9 3.4 6 0.9 TG, mmol/L 2.8 6 3.0 1.9 6 1.3b Glucose, mmol/L 61.2 6 26.3 56.3 6 20.9b Systolic blood pressure, mm Hg 130.3 6 16.1 122.2 6 16.5b Diastolic blood pressure, mm Hg 81.9 6 10.3 77.3 6 10.6b Dietary intake Total energy, kcal/d 2660 6 913 2220 6 804b Proteins, % energy 13.5 6 3.2 14.2 6 3.3b Proteins, g/d 87.9 6 31.1 77.3 6 28.8b Carbohydrates, % energy 55.3 6 9.3 57.6 6 8.3b Carbohydrates, g/d 363 6 126 318 6 122b Fats, % energy 28.4 6 6.3 29.4 6 6.3b Fats, g/d 84.2 6 34.7 73.2 6 33.3b Other characteristics Alcohol consumers, n (%) 986 (85.2) 1294 (53.5)b Daily, n (%) 23 (2.3) 10 (0.8) Weekly, n (%) 270 (27.4) 102 (7.9) Monthly, n (%) 122 (12.4) 82 (6.3) Occasionally, n (%) 571 (57.9) 1100 (85.0) Physical activity, h/wk 6.0 6 10.7 5.6 6 9.8 Daily smokers, n (%) 276 (23.8) 330 (13.6)b Overweight, n (%) 536 (46.7) 996 (41.6)a Obesity, n (%) 362 (31.5) 731 (30.6) ABCA1-R230C variant, n (%) RR 949 (81.8) 2010 (82.7) RC 202 (17.4) 398 (16.4) CC 9 (0.8) 23 (0.9) 1 Values are expressed as mean 6 SD or n (%). Login to comment 76 ABCA1 p.Arg230Cys Association of ABCA1-R230C with metabolic traits. Login to comment 79 ABCA1 p.Arg230Cys Association of ABCA1-R230C with metabolic traits. Login to comment 86 ABCA1 p.Arg230Cys Predicted values were calculated from regression models containing the ABCA1-R230C variant, carbohydrate intake, and the interaction term, adjusted for age, BMI, tobacco smoking, and alcohol consumption (Fig. 4). Login to comment 89 ABCA1 p.Arg230Cys Discussion The R230C variant of the ABCA1 gene is of particular interest because of its epidemiological implications; it is frequent and private to Native American and descendant populations, it has been consistently associated with low HDL-C concentrations in various reports (19,21-23) including the present study, and this variant is known to have a functional effect, decreasing cholesterol efflux in vitro by ~30% (22). Login to comment 90 ABCA1 p.Arg230Cys Predicted values were calculated from regression models containing the ABCA1-R230C variant, carbohydrate intake, and the interaction term, adjusted for age, BMI, tobacco smoking, and alcohol consumption (Fig. 4). Login to comment 91 ABCA1 p.Arg230Cys The highest risk allele frequency was observed in the southern states (11.2%) in accordance with the higher Native American component of these populations and the Amerindian origin of the R230C variant (22,32). Login to comment 93 ABCA1 p.Arg230Cys ABCA1 p.Arg230Cys TABLE 2 Association between ABCA1-R230C polymorphism and serum lipid concentrations stratified by sex1 RR RC CC P2 Men n 766 158 8 Total-C, mmol/L 5.43 (5.31-5.56) 5.08 (4.90-5.27) 5.25 (4.54-6.06) ,0.001 HDL-C, mmol/L 0.97 (0.94-0.99) 0.91 (0.88-0.95) 0.85 (0.72-1.01) 0.002 LDL-C, mmol/L 3.30 (3.18-3.41) 3.08 (2.91-3.25) 4.12 (3.17-5.35) 0.020 Women n 1769 348 22 Total-C, mmol/L 5.39 (5.32-5.45) 5.26 (5.15-5.38) 4.86 (4.49-5.26) 0.010 HDL-C, mmol/L 1.20 (1.18-1.22) 1.09 (1.06-1.12) 1.08 (0.98-1.20) ,0.001 LDL-C, mmol/L 3.30 (3.24-3.36) 3.26 (3.16-3.37) 3.10 (2.76-3.47) 0.328 1 Values are geometric means (95% CI). Login to comment 95 ABCA1 p.Arg230Cys The highest risk allele frequency was observed in the southern states (11.2%) in accordance with the higher Native American component of these populations and the Amerindian origin of the R230C variant (22,32). Login to comment 97 ABCA1 p.Arg230Cys ABCA1 p.Arg230Cys To date, all studies assessing the effect of the ABCA1-R230C variant on HDL-C concentrations in different populations have been consistent. Login to comment 98 ABCA1 p.Arg230Cys As expected, the R230C variant was significantly associated with lower HDL-C concentrations in the ENSADER sample, although the effect of the variant was greater in women than in men. Login to comment 101 ABCA1 p.Arg230Cys To date, all studies assessing the effect of the ABCA1-R230C variant on HDL-C concentrations in different populations have been consistent. Login to comment 102 ABCA1 p.Arg230Cys As expected, the R230C variant was significantly associated with lower HDL-C concentrations in the ENSADER sample, although the effect of the variant was greater in women than in men. Login to comment 108 ABCA1 p.Arg230Cys A sex-specific gene-diet interaction was observed in the present study, because the inverse correlation between carbohydrate intake and HDL-C concentrations was greater in women bearing the R230C variant, particularly in those with a premenopausal status. Login to comment 109 ABCA1 p.Arg230Cys In contrast, the R230C variant and carbohydrate intake showed an independent, nonadditive effect in men. Login to comment 112 ABCA1 p.Arg230Cys A sex-specific gene-diet interaction was observed in the present study, because the inverse correlation between carbohydrate intake and HDL-C concentrations was greater in women bearing the R230C variant, particularly in those with a premenopausal status. Login to comment 113 ABCA1 p.Arg230Cys ABCA1 p.Arg230Cys To our knowledge, this is the first study reporting a sex-specific interaction between any ABCA1 variant and carbohydrate intake on HDL-C concentrations, representing the first effort to evaluate gene-nutrient interactions for the ABCA1-R230C gene variant. Login to comment 117 ABCA1 p.Arg230Cys To our knowledge, this is the first study reporting a sex-specific interaction between any ABCA1 variant and carbohydrate intake on HDL-C concentrations, representing the first effort to evaluate gene-nutrient interactions for the ABCA1-R230C gene variant. Login to comment 190 ABCA1 p.Arg230Cys Villarreal-Molina MT, Aguilar-Salinas CA, Rodrı´guez-Cruz M, Rian˜o D, Villalobos-Comparan M, Coral-Vazquez R, Menjivar M, Yescas- Gomez P, Ko¨nigsoerg-Fainstein M, Romero-Hidalgo S, et al. The ATP-binding cassette transporter A1 R230C variant affects HDL cholesterol levels and BMI in the Mexican population: association with obesity and obesity-related comorbidities. Login to comment 195 ABCA1 p.Arg230Cys Villarreal-Molina MT, Aguilar-Salinas CA, Rodr &#b4;guez-Cruz M, Rian dc;o D, Villalobos-Comparan M, Coral-Vazquez R, Menjivar M, Yescas-Gomez P, Ko &#a8;nigsoerg-Fainstein M, Romero-Hidalgo S, et al. The ATP-binding cassette transporter A1 R230C variant affects HDL cholesterol levels and BMI in the Mexican population: association with obesity and obesity-related comorbidities. Login to comment 199 ABCA1 p.Arg230Cys Association of R230C ABCA1 gene variant with low C-HDL levels and abnormal HDL subclass distribution in Mexican school-aged children. Login to comment 204 ABCA1 p.Arg230Cys Association of R230C ABCA1 gene variant with low C-HDL levels and abnormal HDL subclass distribution in Mexican school-aged children. Login to comment 206 ABCA1 p.Arg230Cys ABCA1 p.Arg230Cys The non-synonymous Arg230Cys variant (R230C) of the ATP-binding cassette transporter A1 is associated with low HDL cholesterol concentrations in Mexican adults: a population based nation wide study. Atherosclerosis. 2011;216:146-50. Login to comment 211 ABCA1 p.Arg230Cys ABCA1 p.Arg230Cys The non-synonymous Arg230Cys variant (R230C) of the ATP-binding cassette transporter A1 is associated with low HDL cholesterol concentrations in Mexican adults: a population based nation wide study. Atherosclerosis. 2011;216:146-50. Login to comment