Background and Aims.Metabolic syndrome (MetS) is a disorder that includes a cluster of several risk factors for the development of type 2 diabetes and cardiovascular disease. The R230C variant of theABCA1gene has been associated with low HDL-cholesterol in several studies, but its association with MetS in children remains to be determined. 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. Methods.The study was performed in seven urban primary schools in the State of Mexico. Four hundred thirty-two Mexican school-age children 6e13 years old were recruited. MetS was identified using the International Diabetes Federation definition. The R230C variant of theABCA1gene was genotyped to seek associations with MetS and other metabolic traits. Results.The prevalence of MetS was 29% in children aged 10e13 years. The R230C variant was not associated with MetS (OR51.65;p50.139). Furthermore, in the whole population, the R230C variant was associated with low HDL-cholesterol levels (bcoefficient5
3.28,p!0.001). Interestingly, in the total population we found a novel association of this variant with high triglyceride levels (b coefficient 514.34; p50.027). Conclusions.We found a new association of the R230C variant of the ABCA1 gene with high triglyceride levels. Our findings also replicate the association of this variant with low HDL-cholesterol levels in Mexican school-age children.

1. 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-Melendez,a
Carlos Galindo-Gomez,a
Liliana Juarez-Martınez,a
F. Enrique Gomez,b
Eulises Diaz-Diaz,c
Marco Antonio Avila-Arcos,a
and Abelardo Avila-Curiela
a
Direccion de Nutricion, b
Departamento de Fisiologıa de la Nutricion, c
Departamento de Biologıa de la Reproduccion,
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico, D.F., Mexico
Received for publication September 28, 2014; accepted July 31, 2015 (ARCMED-D-14-00546).
Background and Aims. Metabolic syndrome (MetS) is a disorder that includes a cluster
of several risk factors for the development of type 2 diabetes and cardiovascular disease.
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. 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.
Methods. The study was performed in seven urban primary schools in the State of
Mexico. Four hundred thirty-two Mexican school-age children 6e13 years old were
recruited. MetS was identified using the International Diabetes Federation definition.
The R230C variant of the ABCA1 gene was genotyped to seek associations with MetS
and other metabolic traits.
Results. The prevalence of MetS was 29% in children aged 10e13 years. The R230C
variant was not associated with MetS (OR 5 1.65; p 5 0.139). Furthermore, in the whole
population, the R230C variant was associated with low HDL-cholesterol levels
(b coefficient 5 À3.28, p !0.001). Interestingly, in the total population we found a novel
association of this variant with high triglyceride levels (b coefficient 5 14.34;
p 5 0.027).
Conclusions. We found a new association of the R230C variant of the ABCA1 gene with
high triglyceride levels. Our findings also replicate the association of this variant with low
HDL-cholesterol levels in Mexican school-age children. Ó 2015 IMSS. Published by
Elsevier Inc.
Key Words: Metabolic syndrome X, Obesity, HDL cholesterol, Triglycerides.
Introduction
Metabolic syndrome (MetS) is a cluster of cardiometabolic
risk factors predisposing to conditions such as type 2 dia-
betes mellitus (T2DM) and cardiovascular disease (1). In
Mexico, according to the results of ENSANUT 2006, the
national prevalence of MetS in adults O20 years of age
was 36.8, 41.6, and 49.8% according to criteria of ATP
III, the American Heart Association/National Heart, Lung,
and Blood Institute, and the International Diabetes Federa-
tion (AHA/NHLBI and IDF), respectively. The MetS
component with the highest prevalence was low high-
density lipoprotein (HDL)-cholesterol, with a prevalence
of 76.3% (2).
HDL-cholesterol formation is the only way by which
excess cholesterol is removed from cells, a process that
involves reverse cholesterol transport (3,4). Excess intracel-
lular cholesterol is removed by ABCA1, a cholesterol
Address reprint requests to: Abelardo Avila-Curiel, MD, Direccion de
Nutricion, Instituto Nacional de Ciencias Medicas y Nutricion Salvador
Zubiran, Vasco de Quiroga #15 Colonia Seccion 16, Tlalpan 14000,
Mexico, D.F.; Phone and Fax: (þ52) (55) 55738350; E-mail: aavila@
slan.org.mx
0188-4409/$ - see front matter. Copyright Ó 2015 IMSS. Published by Elsevier Inc.
http://dx.doi.org/10.1016/j.arcmed.2015.07.008
Archives of Medical Research 46 (2015) 495e501

2. transporter, by cholesterol efflux to apolipoprotein A-1
(ApoA-1), forming nascent HDL particles, which are ester-
ified to form mature HDL particles (4).
Within the ABCA1 gene, genetic variants that affect the
plasma HDL-cholesterol level in various populations have
been described (5). In the Mexican population, the non-
synonymous 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). The functionality of this
variant has also been demonstrated by in vitro studies,
showing a 27% reduction in cholesterol efflux (9). Howev-
er, 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). 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 over-
weight and obesity are prevalent.
Materials and Methods
The study included 432 children (227 boys and 205 girls)
aged 6e13 years, randomly selected from seven elementary
schools in the State of Mexico that participated in the 5th
census of weight and height. Selected schools had a high
prevalence of obesity (O30%) (11). Previously, this study
was approved by the Committees for Research Ethics and
Research of the Instituto Nacional de Ciencias Medicas y
Nutricion Salvador Zubiran (INNSZ). Written informed
consent was obtained from the participants and their par-
ents. Only children whose parents and grandparents were
born in Mexico were selected. Children who were not diag-
nosed with MetS were studied as controls. The use of drugs
for high blood pressure, hyperglycemia or dyslipidemia was
considered an exclusion criterion.
Following the Lohman reference manual, trained and
standardized personnel measured weight, height, and waist
circumference without shoes and in light clothing (12).
Weight was measured with an electronic scale (Seca 872,
Hamburg, Germany), and height was estimated with a
portable wall stadiometer (Seca 206) to the nearest 1 mm.
Waist circumference was measured by taking into account
the midline on both sides of the body between the lower
costal border and the top edge of the iliac crest using a me-
chanical measuring tape (Seca 201) to the nearest 1 mm.
Blood pressure was measured with a digital cuff monitor
(OMRON HEM-7200, Matsusaka, Japan). Body mass in-
dex was calculated as weight in kilograms divided by
height squared in meters (BMI kg/m2
). The z-score was
calculated by sex and age using the World Health Organi-
zation (WHO) reference (13). Venous blood samples were
drawn after a 10-h fast to measure biochemical parameters
and for DNA extraction. Circulating glucose, triglycerides,
total cholesterol, HDL-cholesterol and low-density lipopro-
tein (LDL)-cholesterol were measured by enzymatic color-
imetric assays (Pointe Scientific, Canton, MI) using an
automated biochemical analyzer (Mindray BS-200, Mind-
ray Medical International Limited, Shenzhen, China). Insu-
lin was measured by liquid-phase radioimmunoassay using
a gamma counter (Cobra II, Packard Instrument Company,
Meriden, CT). The Homeostasis Model AssessmenteInsu-
lin Resistance (HOMA1-IR) index was calculated as ([fast-
ing insulin in IU/L] Â [fasting glucose in mmol/L]/22.5) as
described (14). In addition, three other HOMA indices were
obtained: HOMA2%B (measuring b-cell function rate),
HOMA2%S (measuring insulin sensitivity rate), and HO
MA2%IR (the reciprocal of HOMA2%S) (15). These three
parameters were calculated with the HOMA calculator
(http://www.dtu.ox.ac.uk/homacalculator).
Socioeconomic Status
The socioeconomic coefficient was estimated according to
the geographic area of influence for the selected school.
Information was obtained from the National Institute of
Statistics, Geography, and Informatics (INEGI) on the basic
geostatistic area (BGA) of each school. The socioeconomic
coefficient of each BGA was calculated by the statistical
method of principal components. The model chosen al-
lowed for a further explanation of the variance (75%) and
was located in the first component, which included vari-
ables of property ownership, housing characteristics, and
education. Once the socioeconomic coefficients of a BGA
were estimated, an average socioeconomic coefficient was
estimated for each school and was included in the models
of statistical analyses.
Definition of MetS
In our study population, MetS was defined according to the
criteria of the International Diabetes Federation (IDF) in
2007 (16). MetS was considered to be present when a pa-
tient had central abdominal obesity and two or more of
the following clinical manifestations, which were inter-
preted according to IDF definitions as follows: a) abdom-
inal obesity (AO)—defined by a waist circumference
$90th
percentile for age and sex, for which reference tables
of the Mexican-American population were used (17); b) hy-
pertension—considered when the systolic BP $130 and/or
diastolic BP $85 mmHg; c) hyperglycemia—fasting
glucose concentration $100 mg/dL; d) hypoalphalipopro-
teinemia—HDL #40 mg/dL; e) hypertriglyceridemia—
triglycerides $150 mg/dL.
DNA Extraction
Genomic DNA was obtained from whole blood using a
commercial kit (QIAamp 96 DNA Blood Kit, Qiagen,
496 Gamboa-Melendez et al./ Archives of Medical Research 46 (2015) 495e501

3. Valencia, CA). The R230C variant of the ABCA1 gene was
genotyped using the TaqMan probe (Perkin-Elmer, Wal-
tham, MA) specifically designed for SNP rs9282541 using
the Rotor-Gene Q 5-Plex thermal cycler with high-
resolution melting (HRM) channel (Qiagen). Different ge-
notypes were not observed in 15 duplicate samples (a
quality control), and O98% of the samples produced a
definitive genotype. Deviation from Hardy-Weinberg
equilibrium was not observed for this variant in the
population.
Statistical Analysis
Anthropometric and biochemical data were evaluated using
skewness and kurtosis tests. Data were not normally distrib-
uted; therefore, non-parametric tests were used for the anal-
ysis. 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. Genotype frequency in each group and confor-
mity with Hardy-Weinberg equilibrium were determined
using R software v.2.7.1. All genetic association analyses
were performed using an additive genetic model. The asso-
ciation between the R230C variant and MetS was analyzed
by logistic regression models adjusted for age, sex, BMI z-
score, and socioeconomic status. 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. Data were processed using the STATA/SE 9.1
statistical package (StataCorp LP, College Station, TX).
Results
In Table 1 data are presented either as percentages or as me-
dians (25th
e75th
percentiles). In accordance with the IDF
criteria for MetS, we stratified the sample by age groups:
children aged 6e9 years and children aged 10e13 years
where the medians of anthropometric and biochemical
measurements in children were compared between these
groups. Children aged 10e13 years showed significantly
higher BMI, waist circumference, systolic and diastolic
blood pressure, plasma glucose, plasma insulin, HOMA1-
IR, HOMA2%S, and HOMA2-IR. No significant differ-
ences were found in sex, HOMA2-%B, total cholesterol,
triglycerides, HDL-cholesterol and LDL-cholesterol. Using
the IDF definition for MetS, the prevalence of the syndrome
in children aged 10e13 years old was 29.0%.
The prevalence of the risk allele T (also called C230) in
the study population was 11.9%. Table 2 shows the risk
allele frequency in the total population and each of the traits
of MetS. We evaluated the R230C variant and its relation-
ship with MetS and its components. Taking into account
only 10- to 13-year-old children as reported by IDF criteria,
we found no association with MetS (OR 5 1.65,
p 5 0.139). 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. Anthropometric, clinical, and metabolic characteristics of the study population according to age group
Children aged 6e9 years (n [ 225) Children aged 10e13 years (n [ 207) Total population (n [ 432)
Sex
Female 50.67% 43.96% 47.45%
Male 49.33% 56.04% 52.55%
Metabolic syndrome NA 28.99% NA
Age (years) 8.57 (7.73e9.38) 11.39 (10.65e11.83)a
9.85 (8.52e11.33)
BMI (kg/m2
) 23.05 (20.97e24.86) 26.30 (23.84e28.03)a
24.33 (21.83e26.83)
BMI z-score 2.70 (2.08e3.14) 2.54 (2.05e2.87)a
2.61 (2.06e2.96)
Waist circumference (cm) 76.3 (70.4e82.0) 85.9 (79.6e91.3)a
80.95 (73.1e87.3)
SBP (mmHg) 107.0 (101.0e115.0) 115.0 (108.0e123.0)a
112.0 (104.0e120.0)
DBP (mmHg) 65.0 (59.0e72.0) 68.8 (62.0e73.0)a
67.0 (61.0e73.0)
Glucose (mg/dL) 93.0 (89.0e96.0) 95.0 (91.0e100.0)a
94.0 (90.0e98.0)
Insulin (mU/mL) 12.83 (8.20e19.51) 16.07 (10.12e23.04)a
14.31 (8.69e21.35)
InHOMA (HOMA1-IR) 2.88 (1.90e4.58) 3.79 (2.36e5.46)a
3.33 (2.00e4.94)
HOMA2-% B 113.9 (85.7e150.4) 124.9 (90.6e163.4) 117.5 (87.9e158.6)
HOMA2-% S 69.1 (46.1e108.5) 55.4 (39.2e87.2)a
62.1 (41.7e99.8)
HOMA2-IR 1.45 (0.92e2.17) 1.81 (1.15e2.55)a
1.61 (1.00e2.40)
Total cholesterol (mg/dL) 161.0 (143.0e180.0) 164.0 (146.0e186.0) 162.0 (144.0e183.5)
Triglycerides (mg/dL) 119.0 (79.0e160.0) 121.0 (91.0e167.0) 121.0 (83.5e162.5)
HDL (mg/dL) 40.0 (35.0e48.0) 40.0 (35.0e46.0) 40.0 (35.0e47.0)
LDL (mg/dL) 104.0 (90.0e123.0) 106.0 (89.0e126.0) 105.0 (89.0e124.0)
NA, not applicable; 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 between children aged 6e9 years and children aged 10e13 years ( p !0.05).
497Association of R230C with High Triglycerides in Children

4. old (Table 2). Table 3 compares clinical and metabolic
characteristics of the population by genotype groups. In at
least one of the groups of genotypes containing the risk
allele (T), HDL-c levels are significantly lower. Median tri-
glyceride concentrations have higher values in children
who carry genotypes containing the risk allele (R230C
and C230C).
In addition, we found a statistically significant associa-
tion 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). We also found
that this variant was associated with lower systolic
(b 5 À2.25; p 5 0.047) and diastolic blood pressure
(b 5 À2.19; p 5 0.041). Interestingly, we found a novel as-
sociation of this variant with high triglyceride levels
(b 5 14.34; p 5 0.027) in the whole population. Finally,
R230C was not associated with any of the other quantitative
traits evaluated (Table 4).
Discussion
MetS is a cluster of risk factors that predict the develop-
ment of cardiovascular disease and T2DM (1,18). The prev-
alence of MetS in adults is paralleled by that of obesity, and
this situation is similar in children and adolescents. There-
fore, 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. We found a
novel association of R230C variant with high triglyceride
Table 2. 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.
Logistic regression analysis using an additive genetic model adjusted for age, sex, BMI z-score, and socioeconomic status.
Statistically significant observations are in bold.
a
Cutoffs for each trait are described in Materials and Methods.
b
The model was adjusted for age, sex, and socioeconomic status.
Table 3. Clinical and metabolic characteristics of the population stratified by genotype groups
TRAIT
R230C variant, additive model
pR230R (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.
498 Gamboa-Melendez et al./ Archives of Medical Research 46 (2015) 495e501

5. levels (b 5 14.34, p 5 0.027). In addition, we replicated its
association with low HDL-cholesterol levels (b 5 À3.28,
p !0.001). However, the R230C variant was not associated
with MetS (OR 5 1.65; p 5 0.139).
This study was conducted in a high-risk school-aged
population, given that the prevalence of obesity in public
schools in the State of Mexico is O30% (11). The risk
allele frequency in our study was 0.119, one of the highest
reported in a Mexican mestizo population (6e8,10,19).
However, most indigenous groups in Mexico have a higher
risk allele frequency (Maya 0.280, Purepecha 0.210, Yaquis
0.200, and Teenek 0.170), given that it is an American
variant inherited by Native Americans, which suggests it
has been positively selected (9). A recent study suggests
that the domestication of maize was one of the evolutionary
forces that increased the frequency of this variant in
America, representing an example of ‘‘gene-culture’’
coevolution (20).
In this regard, the R230C variant of the ABCA1 gene was
first reported in subjects with familial hypoalphalipoprotei-
nemia in an Oji-Cree population (21). Subsequently, it was
studied in the Mexican population where it was associated
with low HDL-cholesterol, MetS, obesity, and T2DM (6,7).
In our study, according to the IDF criteria, the R230C
variant was not associated with MetS (OR 5 1.65;
p 5 0.139). Although there is a definition of the IDF for
MetS, most studies have used various definitions of pediat-
ric MetS based on modified adult criteria with varied sets of
criteria and different cut-off values (22e30). The use of
different definitions has led to significant discrepancies in
determining overall MetS prevalence as well as impairing
comparisons across studies. Because of this, we apply the
sets of criteria and cut-off values according to the IDF
definition.
This is the second study in which the R230C variant was
analyzed in a Mexican school-aged population. We
confirmed the association with low HDL-cholesterol levels.
Additionally, Flores-Dorantes et al. revealed the involve-
ment of this variant in the regulation of the distribution of
HDL-cholesterol subclasses (10). 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). Interestingly, we found a novel association of the
R230C variant with increased triglyceride levels in the pre-
sent study. Consistent with this, we found higher values of
median triglyceride concentrations in children who carry
genotypes containing the risk allele (Table 3). A report
showed a positive correlation between BMI and triglyceride
levels in both men and women (31). However, the effect of
BMI on triglyceride levels was greater in women carrying
the risk allele of the R230C variant probably (31). This
finding may be related with our result because there are
different body distribution between children and adults;
nonetheless, additional studies are necessary. Although
some reports have shown a tendency of higher triglycerides
in those subjects with the risk variant genotype in a domi-
nant model (R230C/C230C), their results failed to reach
statistical significance (7,8,31,32). For this reason, more
studies are needed with larger sample sizes to validate this
finding.
The present study has two important limitations. The
first is the lack of assessment of pubertal status or sexual
development of the children and the second is the lack of
genetic ancestry markers. Unfortunately, the pubertal stage
was not measured in our study and we cannot discriminate
the potential influence of this variable on the associations
evaluated. Normally, pubertal status assessment is per-
formed in clinical practice with the Tanner test; however,
in epidemiological studies, this test is unlikely to be
performed because it involves psychosocial and physical
barriers and other ethical considerations. However, the
results of a study that analyzed this variant in school-age
children and the association with HDL levels showed that
the adjustment for pubertal status did not affect the associ-
ation (10). Furthermore, Hirschler et al. found no signifi-
cant differences in the distribution of Tanner stage
between groups with and without MetS (33).
The second limitation involved the lack of genetic
ancestry markers for our study population. 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. Effect of the genotype of ABCA1 gene variant on the anthropometric, clinical, and metabolic characteristics, according to age group
Children aged 6e9 years (n [ 225) Children aged 10e13 years (n [ 207) Total population (n [ 432)
Coef. b (95% CI) p Coef. b (95% CI) p Coef. b (95% CI) p
SBP (mmHg) À1.76 (À4.78, 1.26) 0.252 À2.65 (À5.97, 0.67) 0.117 L2.25 (L4.46, L0.03) 0.047
DBP (mmHg) L3.33 (L6.57, L0.09) 0.044 À0.29 (À2.79, 2.22) 0.822 L2.19 (L4.30, 0.09) 0.041
TC (mg/dL) L8.79 (L17.32, L0.26) 0.044 1.66 (À7.13, 10.45) 0.709 À3.94 (À10.02, 2.15) 0.204
TG (mg/dL) 10.54 (À5.07, 26.16) 0.185 18.98 (À1.86, 39.82) 0.074 14.34 (1.61, 27.08) 0.027
HDL (mg/dL) L3.94 (L6.15, L1.73) 0.001 L2.50 (L4.93, L0.07) 0.044 L3.28 (L4.91, L1.64) !0.001
SBP, systolic blood pressure; DBP, diastolic blood pressure; TC, total cholesterol; TG, triglycerides; HDL, high-density lipoprotein.
Linear regression analyses adjusted for age, sex, socioeconomic status, and BMI z-score were performed, and the coefficient b is shown (95% CI);
( p !0.05).
Statistically significant observations are in bold.
499Association of R230C with High Triglycerides in Children

6. mainly inhabited by a mixed population (mestizos) derived
from three ancestral components (34). The main ancestral
component comes from Native Americans (original inhab-
itants), whereas the second comes from the Europeans and
the third from West Africa. Due to historical events, the
mixture of these ethnicities is relatively recent, which partly
explains the genetic stratification of the Mexican mestizo
population. The control of population stratification has been
suggested as a confounding variable in the association
studies carried out in these populations (35). Although
these markers were not used in this study, we aimed to over-
come this limitation through the existing relationship
between socioeconomic status and Amerindian ancestry.
This study included socioeconomic status as a proxy vari-
able for ancestry, based on studies reporting a strong asso-
ciation of Amerindian ancestry with low socioeconomic
status in different populations (35e40). Additionally, one
study suggests that social stratification, also known as ‘‘as-
sortative mating’’, is closely related to socioeconomic
status, which could explain its correlation with genetic
stratification (35). Based on these studies, we included
socioeconomic status in our association models to compen-
sate for the lack of data on ancestry.
In conclusion, our findings confirmed the association of
the R230C variant of the ABCA1 gene with low HDL-
cholesterol in Mexican school-aged children. Additionally,
we found a new association of this variant with high triglyc-
eride levels. However, we found no evidence of association
of this variant with MetS.
Acknowledgments
We thank Dr. Hortensia Moreno Macıas for suggestions regarding
this study and also Jessica Moreno Saracho for help with manu-
script editing.
This project was supported by the System for Integral Family
Development (DIF) of the State of Mexico.
Conflict of interest: No potential conflicts of interest relevant to
this article were reported.
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501Association of R230C with High Triglycerides in Children