Association of R230C ABCA1 gene variant with low HDL-C levels and abnormal HDL subclass distribution in Mexican school-aged children

Flores-Dorantes, María Teresa; Arellano-Campos, Olimpia; Posadas-Sánchez, Rosalinda; Villarreal-Molina, Teresa; Moeini, Aida; Romero‐Hidalgo, Sandra; Yescas-Gómez, Petra; Pérez-Méndez, Óscar; Jorge‐Galarza, Esteban; Tusié-Luna, Teresa; Villalobos-Comparán, Marisela; Jacobo-Albavera, Leonor; Villamil‐Ramírez, Hugo; López-Contreras, Blanca E.; Aguilar-Salinas, Carlos A.; Posadas‐Romero, Carlos; Canizales‐Quinteros, Samuel

doi:10.1016/j.cca.2010.04.025

Cited by 20 publications

(18 citation statements)

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“…Heritability estimates for HDL-C levels mostly range between 40 and 60% (14) and various genetic polymorphisms of the ABCA1 gene have been associated with HDL-C concentrations in several populations (15)(16)(17)(18). 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)(20)(21)(22)(23). This allele is of particular interest, because it is frequent in the Mexican mestizo population (;10%) and the sole presence of the C risk allele explains almost 4% of plasma HDL-C concentration variation, which is higher than all HDL-C variation associated with a single nucleotide polymorphism identified through genome-wide association studies in European and Asian populations (24).…”

Section: Introductionmentioning

confidence: 98%

Carbohydrate Intake Modulates the Effect of the ABCA1 -R230C Variant on HDL Cholesterol Concentrations in Premenopausal Women

Romero‐Hidalgo

Villarreal-Molina

González-Barrios

et al. 2012

The Journal of Nutrition

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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. However, information on how diet composition modifies the effect of the ABCA1-R230C variant on HDL-C concentrations is very scarce. 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. 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. Statistical analyses consisted of simple linear and multiple regression modeling adjusting for age, BMI, smoking, and alcohol consumption. The overall C risk allele frequency was 9.3% and the variant was significantly associated with low HDL-C concentrations in both sexes. 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). In conclusion, the effect of the ABCA1-R230C gene variant on HDL-C concentrations is modulated by carbohydrate intake in premenopausal women. This finding may help design optimized dietary interventions according to sex and ABCA1-R230C genotype.

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Section: Introductionmentioning

confidence: 98%

Carbohydrate Intake Modulates the Effect of the ABCA1 -R230C Variant on HDL Cholesterol Concentrations in Premenopausal Women

Romero‐Hidalgo

Villarreal-Molina

González-Barrios

et al. 2012

The Journal of Nutrition

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“…In this study, we investigated the influence of polymorphisms in the ABCA1 genes on HDL levels, BMI, and age of disease onset among T2DM patients. Previous studies have shown how ABCA1 polymorphisms influence HDL-cholesterol levels in diabetes patients 24 and in the general population 16,19,[25][26][27][28] . One of the well-studied variants with documented corresponding lipid profiles is rs2230806 (R219K); however, the results are inconsistent across various studies.…”

Section: Discussionmentioning

confidence: 99%

“…Several ABCA1 polymorphisms and mutations have been reported to be associated with HDL cholesterol levels 16,17 obesity 16 , and T2DM 20,21 , across multiple ethnic groups [16][17][18][19][20][21] . In this study, we investigated the influence of polymorphisms in the ABCA1 genes on HDL levels, BMI, and age of disease onset among T2DM patients.…”

Section: Discussionmentioning

confidence: 99%

“…There is genetic evidence that ABCA1 is involved in modulating T2DM in humans. Several ABCA1 polymorphisms and mutations have been reported to decrease HDL cholesterol levels [16][17][18][19] , obesity 16 , and T2DM 20, 21 across multiple ethnic groups. In the Mexican population, subjects with the R230C polymorphism (rs9282541) in the ABCA1 gene have low HDL 19 , increased body mass 16 , elevated haemoglobin A 1c levels, reduced fasting insulin, and early-onset T2DM 22 .…”

Section: Introductionmentioning

confidence: 99%

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Association of adenosine triphosphate-binding cassette transporter A1 gene polymorphism with lipid profiles and early-onset type 2 diabetes

Lu¹,

Liao²,

Wang³

et al. 2014

ScienceAsia

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Adenosine triphosphate-binding cassette transporter A1 (ABCA1) plays an important role in lipid metabolism and is involved in diabetes. We investigated the associations between lipid profiles and an early-onset diabetic phenotype with ABCA1 genotypes among 999 type 2 diabetes mellitus patients in the Han Chinese population of Taiwan. During study enrolment, blood samples were collected by venipuncture from these patients for genomic DNA isolation and serological tests, and data related to the diabetes age of onset were collected using a self-report questionnaire. Four single-nucleotide polymorphisms (SNPs) were selected for genotyping by polymerase chain reaction in each patient. The present study found that the high-density lipoprotein (HDL) levels were significantly different among patients with different genotypes at SNP rs2487039 (p = 0.018). The body mass index (BMI) was also significantly different among patients with different genotypes at SNP rs2487039, rs2230806, and rs200069 (p = 0.009, 0.004, and 0.003, respectively). The polymorphisms at position rs10121901 in ABCA1 were statistically associated with development of early-onset type 2 diabetes mellitus (p = 0.013), with an odds ratio of 0.78 (95% confidence interval: 0.64-0.95). In conclusion, an ABCA1 variant is associated with HDL level, BMI, and early-onset type 2 diabetes mellitus in a specific Taiwanese population.

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“…In the first case, individuals were selected from patients who arrived at the hospital for treatment; in the second case, the samples were obtained from a group recruited from a summer camp for children of employees of the Mexican Health Ministry and from a public junior high school in Mexico City. 24 Bioinformatic analysis has suggested the functionality of the rs13306560 polymorphism and that the ancestral allele G is conserved in higher vertebrates. 7 Additional analysis conducted by our group showed that this polymorphism is located at −23 bp from the transcription start site, a segment that may be within the basal promoter of the MTHFR.…”

Section: Discussionmentioning

confidence: 99%

Functional Polymorphism rs13306560 of the MTHFR Gene Is Associated With Essential Hypertension in a Mexican-Mestizo Population

Pérez-Razo

Cano-Martínez

Alarcón

et al. 2015

Circ Cardiovasc Genet

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H ypertension is a common condition that according to a global study will affect 1.56 billion adults by the year 2025.1 Despite this, essential hypertension (EH) remains as a complex phenotype in which genetic determinants remain largely undefined. 2,3 A recent large study of Sardinian families estimated a broad-sense heritability of ≈65% and ≈45% for systolic and diastolic blood pressure (BP), respectively. 4 In general, large-scale epidemiological studies suggest that the heritability of BP exceeds 50%, justifying a search for genetic variants influencing susceptibility to EH. 5,6 Indeed, the human genome contains several genetic variants that may influence the BP and have been associated with hypertension. 7,8 In this regard, the AGTRAP-MTHFR-CLCN6-NPPA-NPPB gene cluster at 1p36 has been associated with cardiac dysfunction, BP, and renal disease.2,9-11 MTHFR is a key element within this gene cluster that codifies for the enzyme methylenetetrahydrofolate reductase, which catalyzes the reduction of 5,10-methylenetetrahydrofolate to 5 methyltetrahydrofolate, a cosubstrate Background-Polymorphisms of methylenetetrahydrofolate reductase (MTHFR) have been associated with diastolic blood pressure, hypertension, and other cardiovascular diseases; however, results of these studies are still controversial. In this study, we sought to determine whether 2 functional variants (rs1801133 and rs13306560) within the MTHFR are associated with hypertension in Mexican-Mestizos. Methods and Results-We performed a case-control study with 1214 subjects including adults and children to test for the association of both single nucleotide polymorphisms with essential hypertension. The adult group included 764 participants (372 patients and 391 controls) and the group of children included 418 participants (209 patients and 209 controls). rs13306560 was associated with essential hypertension in adults (odds ratio, 4.281; 95% confidence interval, 1.841-9.955; P=0.0003) with a statistical power >0.8. In children, none of the polymorphisms was associated with essential hypertension. In addition, we assessed the effect of the rs13306560 polymorphism on the MTHFR promoter region by means of luciferase reporter gene assays using human umbilical vein endothelial cells. Cells transfected with the pMTHFRaLUC construct showed an ≈25% reduction in luciferase activity (P=0.003). Furthermore, the promoter activity was reduced considerably by in vitro methylation of CpG sequences. Conclusions-Our data suggest that the rs13306560 polymorphism of the MTHFR may be part of the observed hypertension process in Mexican-Mestizo populations, but further studies are warranted. In addition, the allele A of the rs13306560 polymorphism as well as the in vitro methylation of CpGs reduced the promoter activity of the MTHFR regulatory region. for homocysteine remethylation to methionine. 12 The T allele of the rs1801133 (formerly C677T or A222V) generates an MTHFR thermolabile enzyme with reduced activity, and the homozygous state of this allele has been associated...

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Association of R230C ABCA1 gene variant with low HDL-C levels and abnormal HDL subclass distribution in Mexican school-aged children

Cited by 20 publications

References 41 publications

Carbohydrate Intake Modulates the Effect of the ABCA1 -R230C Variant on HDL Cholesterol Concentrations in Premenopausal Women

Carbohydrate Intake Modulates the Effect of the ABCA1 -R230C Variant on HDL Cholesterol Concentrations in Premenopausal Women

Association of adenosine triphosphate-binding cassette transporter A1 gene polymorphism with lipid profiles and early-onset type 2 diabetes

Functional Polymorphism rs13306560 of the MTHFR Gene Is Associated With Essential Hypertension in a Mexican-Mestizo Population

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