ABCMdb

PMID: 26256050

Gamboa-Melendez MA, Galindo-Gomez C, Juarez-Martinez L, Gomez FE, Diaz-Diaz E, Avila-Arcos MA, Avila-Curiel A
Novel association of the R230C variant of the ABCA1 gene with high triglyceride levels and low high-density lipoprotein cholesterol levels in Mexican school-age children with high prevalence of obesity.
Arch Med Res. 2015 Aug;46(6):495-501. doi: 10.1016/j.arcmed.2015.07.008. Epub 2015 Aug 6., [PubMed]

Sentences

No. Mutations Sentence Comment

0 ABCA1 p.Arg230Cys ORIGINAL ARTICLE Novel Association of the R230C Variant of the ABCA1 Gene with High Triglyceride Levels and Low High-density Lipoprotein Cholesterol Levels in Mexican School-age Children with High Prevalence of Obesity Marco Alberto Gamboa-Mel endez,a Carlos Galindo-G omez,a Liliana Ju arez-Mart nez,a F. Enrique G omez,b Eulises Diaz-Diaz,c Marco Antonio Avila-Arcos,a and Abelardo Avila-Curiela a Direcci on de Nutrici on, b Departamento de Fisiolog a de la Nutrici on, c Departamento de Biolog a de la Reproducci on, Instituto Nacional de Ciencias M edicas y Nutrici on Salvador Zubir an, M exico, D.F., Mexico Received for publication September 28, 2014; accepted July 31, 2015 (ARCMED-D-14-00546). Login to comment 3 ABCA1 p.Arg230Cys The R230C variant of the ABCA1 gene has been associated with low HDL-cholesterol in several studies, but its association with MetS in children remains to be determined. Login to comment 4 ABCA1 p.Arg230Cys The aim of this study was to analyze the association of the R230C variant with MetS and other metabolic traits in school-aged Mexican children. Login to comment 9 ABCA1 p.Arg230Cys The R230C variant of the ABCA1 gene was genotyped to seek associations with MetS and other metabolic traits. Login to comment 12 ABCA1 p.Arg230Cys The R230C variant was not associated with MetS (OR 5 1.65; p 5 0.139). Login to comment 13 ABCA1 p.Arg230Cys Furthermore, in the whole population, the R230C variant was associated with low HDL-cholesterol levels (b coefficient 5 3.28, p !0.001). Login to comment 16 ABCA1 p.Arg230Cys We found a new association of the R230C variant of the ABCA1 gene with high triglyceride levels. Login to comment 27 ABCA1 p.Arg230Cys In the Mexican population, the nonsynonymous R230C variant (rs9282541) of the ABCA1 gene has been consistently associated with low HDL-cholesterol, whereas in some studies it has been associated with obesity and MetS (6e8). Login to comment 29 ABCA1 p.Arg230Cys ABCA1 p.Arg230Cys However, there has been only one report studying the R230C variant in children, which found an association between R230C and low HDL-cholesterol in school-aged children (10). Login to comment 30 ABCA1 p.Arg230Cys In the present study we evaluated the R230C variant of the ABCA1 gene and its relationship to MetS and its components in a population of children attending public elementary schools in the State of Mexico where overweight and obesity are prevalent. Login to comment 56 ABCA1 p.Arg230Cys The R230C variant of the ABCA1 gene was genotyped using the TaqMan probe (Perkin-Elmer, Waltham, MA) specifically designed for SNP rs9282541 using the Rotor-Gene Q 5-Plex thermal cycler with high-resolution melting (HRM) channel (Qiagen). Login to comment 61 ABCA1 p.Arg230Cys Differences in anthropometric, clinical, and metabolic characteristics of the study population were compared using the Kruskal-Wallis test for continuous variables and c2 test for categorical variables according to age group and R230C genotype. Login to comment 63 ABCA1 p.Arg230Cys The association between the R230C variant and MetS was analyzed by logistic regression models adjusted for age, sex, BMI z-score, and socioeconomic status. Login to comment 64 ABCA1 p.Arg230Cys The association between the R230C variant and quantitative variables was analyzed using multiple linear regression models adjusted for age, sex, socioeconomic status, and BMI z-score when applicable. Login to comment 73 ABCA1 p.Arg230Cys We evaluated the R230C variant and its relationship with MetS and its components. Login to comment 75 ABCA1 p.Arg230Cys Interestingly, an association of the R230C variant with hypoalphalipoproteinemia (OR 5 2.92, p 5 0.001) was shown only in children aged 6e9 years Table 1. Login to comment 80 ABCA1 p.Arg230Cys Median triglyceride concentrations have higher values in children who carry genotypes containing the risk allele (R230C and C230C). Login to comment 81 ABCA1 p.Arg230Cys ABCA1 p.Arg230Cys In addition, we found a statistically significant association of the R230C variant with low HDL-cholesterol levels ( p !0.001); our data imply that for every risk allele unit of this R230C variant there is a decrease of 3.28 mg/dl in plasma HDL-cholesterol levels (Table 4). Login to comment 84 ABCA1 p.Arg230Cys Finally, R230C was not associated with any of the other quantitative traits evaluated (Table 4). Login to comment 87 ABCA1 p.Arg230Cys Therefore, we evaluated whether the non-synonymous R230C variant (rs9282541) of the ABCA1 gene was associated with MetS and whether we could replicate its association with low HDL-cholesterol in a population of children in public elementary schools of the State of Mexico. Login to comment 88 ABCA1 p.Arg230Cys We found a novel association of R230C variant with high triglyceride Table 2. Login to comment 89 ABCA1 p.Arg230Cys Analysis of association of R230C variant abdominal obesity, hypertension, hyperglycemia, hypertriglyceridemia, and hypoalphalipoproteinemia by age groups TRAITa Risk allele frequency (T) Children aged 6e9 years, n [ 225 Children aged 10e13 years, n [ 207 All, n [ 432 Without trait, n [ 275 With trait, n [ 157 OR (95% CI) p OR (95% CI) p AOb 0.119 0.098 0.128 1.31 (0.69e2.49) 0.404 1.16 (0.59e2.30) 0.665 Hypertension 0.119 0.124 0.078 0.40 (0.10e1.65) 0.203 0.80 (0.30e2.14) 0.650 Hyperglycemia 0.119 0.120 0.118 0.99 (0.46e2.15) 0.983 0.93 (0.47e1.87) 0.846 Hypertriglyceridemia 0.119 0.103 0.153 1.55 (0.85e2.81) 0.152 1.39 (0.73e2.65) 0.318 Hypoalphalipoproteinemia 0.119 0.081 0.167 2.92 (1.56e5.48) 0.001 1.65 (0.88e3.07) 0.117 NA, not applicable; AO, abdominal obesity; OR, odds ratio. Login to comment 94 ABCA1 p.Arg230Cys ABCA1 p.Arg230Cys Clinical and metabolic characteristics of the population stratified by genotype groups TRAIT R230C variant, additive model p R230R (CC) R230C (CT) C230C (TT) BMI (kg/m2 ) 24.2 (21.60e26.84) 24.9 (22.49e27.09) 24.0 (22.92e26.58) 0.575 BMI z-score 2.58 (2.01e2.97) 2.65 (2.31e3.01) 2.70 (2.42e2.91) 0.495 Waist circumference (cm) 81.2 (72.6e87.2) 81.1 (73.04e89.0) 78.8 (74.0e83.0) 0.721 SBP (mmHg) 112.0 (104.0e120.0) 112.0 (104.0e118.0) 102.5 (97.0e107.0) 0.078 DBP (mmHg) 67.0 (61.0e73.0) 65.0 (60.0e72.0) 63.0 (58.0e72.0) 0.267 Glucose (mg/dL) 94.0 (90.0e98.0) 94.0 (91.0e99.0) 93.5 (89.0e97.0) 0.582 Insulin (mU/mL) 14.37 (8.60e20.79) 13.3 (9.56e24.97) 14.7 (10.32e19.70) 0.755 InHOMA (HOMA1-IR) 3.38 (1.95e4.79) 3.12 (2.09e5.82) 3.36 (2.45e4.19) 0.775 HOMA2-% B 117.5 (87.6e157.1) 119.5 (90.5e161.5) 127.3 (90.7e177.2) 0.800 HOMA2-% S 61.7 (43.0e102.5) 66.4 (36.5e91.6) 62.5 (47.5e84.9) 0.752 HOMA2-IR 1.62 (0.98e2.33) 1.51 (1.09e2.74) 1.66 (1.18e2.11) 0.752 Total cholesterol (mg/dL) 163.0 (145.0e184.0) 158.0 (142.0e180.0) 158.5 (129.0e172.0) 0.280 Triglycerides (mg/dL) 118 (80.0e154.0) 126.0 (95.0e199.0) 151 (104.0e172.0) 0.045a HDL-cholesterol (mg/dL) 41.0 (36.0e48.0) 37.0 (33.0e45.0) 34 (33.0e40.0) 0.0002a LDL-cholesterol (mg/dL) 106.0 (90.0e124.0) 103.0 (88.0e126.0) 98.5 (84.0e123.0) 0.827 SBP, systolic blood pressure; DBP, diastolic blood pressure. Medians (25th e75th percentiles) are shown because the data do not show normal distribution. For comparison of groups, non-parametric Kruskal-Wallis test was performed. Statistically significant observations are in bold. a Significant differences of the population stratified by genotype groups. Login to comment 97 ABCA1 p.Arg230Cys However, the R230C variant was not associated with MetS (OR 5 1.65; p 5 0.139). Login to comment 102 ABCA1 p.Arg230Cys In this regard, the R230C variant of the ABCA1 gene was first reported in subjects with familial hypoalphalipoproteinemia in an Oji-Cree population (21). Login to comment 104 ABCA1 p.Arg230Cys In our study, according to the IDF criteria, the R230C variant was not associated with MetS (OR 5 1.65; p 5 0.139). Login to comment 108 ABCA1 p.Arg230Cys This is the second study in which the R230C variant was analyzed in a Mexican school-aged population. Login to comment 111 ABCA1 p.Arg230Cys Acu~ na-Alonzo et al. also found that R230C variant decreases cholesterol efflux by 27% in vitro and showed that it is a functional variant (9). Login to comment 112 ABCA1 p.Arg230Cys Interestingly, we found a novel association of the R230C variant with increased triglyceride levels in the present study. Login to comment 115 ABCA1 p.Arg230Cys However, the effect of BMI on triglyceride levels was greater in women carrying the risk allele of the R230C variant probably (31). Login to comment 117 ABCA1 p.Arg230Cys Although some reports have shown a tendency of higher triglycerides in those subjects with the risk variant genotype in a dominant model (R230C/C230C), their results failed to reach statistical significance (7,8,31,32). Login to comment 126 ABCA1 p.Arg230Cys Although most reports evaluating the R230C variant of the ABCA1 gene did not take into account ancestry, a recent report revealed the importance to consider this factor because Mexico is Table 4. Login to comment 137 ABCA1 p.Arg230Cys In conclusion, our findings confirmed the association of the R230C variant of the ABCA1 gene with low HDL-cholesterol in Mexican school-aged children. Login to comment