Special Section on Obesity
Original Article
Association Study of Candidate Gene Polymorphisms and Obesity in a Young Mexican-American Population from South Texas

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Background and Aims

Obesity is increasingly a health problem and a risk factor for diabetes in young Mexican-American populations. Genetic association studies in older, mostly non-Hispanic populations have reported that polymorphisms in the candidate genes HSD11B1, CRP, ADIPOQ, PPARG, ANKK1, ABCC8 and SERPINF1 are associated with obesity or diabetes. We analyzed the polymorphisms rs846910, rs1205, rs1501299, rs1801282, rs1800497, rs757110 and rs1136287 in these candidate genes, for association with obesity and metabolic traits in a young Mexican-American population from south Texas.

Methods

Genotyping of the seven common SNPs were performed by allelic discrimination assays in 448 unrelated Mexican Americans (median age = 16 years) from south Texas. χ2 tests and regression analyses using additive models were used for genetic association analyses adjusting for covariates; p values were corrected for multiple testing by permutation analyses.

Results

rs1800497 (ANKK1) shows association with waist circumference (p = 0.009) and retains the association (p = 0.03) after permutation testing. Analysis of metabolic quantitative traits shows that rs846910 (HSD11B1) was associated with HOMA-IR (p = 0.04) and triglycerides (p = 0.03), and rs1205 (CRP) with HOMA-IR (p = 0.03) and fasting glucose levels (p = 0.007). However, the quantitative traits associations are not maintained after permutation analysis. None of the other SNPs in this study showed associations with obesity or metabolic traits in this young Mexican-American population.

Conclusions

We report a potential association between rs1800497 (linked to changes in brain dopamine receptor levels) and central obesity in a young Mexican-American population.

Introduction

Obesity and overweight represent health problems that are risk factors for the development of other chronic conditions such as diabetes, cancer and cardiovascular disease (CVD) (1). According to the information provided by the National Health and Nutrition Examination Survey (NHANES) in the U.S., the prevalence of obesity in persons >20 years is 33.9%. However, this number increases to 39.3% in the Mexican-American population (2). It has also been suggested that Mexican immigrants have a 64% higher chance to develop the obese phenotype than US-born whites (3). In the southernmost region of Texas, in the Rio Grande Valley (RGV), a recent socioeconomic study shows that prevalence of obesity in an older Mexican-American population ranges from 55.5–57%, the highest rate observed nationwide (4). In younger Mexican Americans, the increasing rates of obesity, metabolic syndrome (MetS) or type 2 diabetes (T2D) are disproportionately higher than in other populations 5, 6. In a study of adolescent Mexican-Americans in RGV, 50% are either overweight or obese, 41% have central obesity and 27% exhibited insulin resistance (7). Environmental factors such as reduced physical activity, intake of energy-dense food and/or cultural and socioeconomic factors play an important role in the development of obesity (8). However, evidence from recent studies suggests that genetic factors account for 40–90% of the body mass index (BMI) variations among populations (9). The future of medicine, whether it is prevention, diagnosis, and therapeutic care for human diseases includes personalized genomics. This involves the identification of genetic factors that confer risk of susceptibility to obesity and related metabolic abnormalities in individuals.

More than 127 biologically relevant candidate genes with DNA variations associated with obesity-related phenotypes have been identified (10). In the present study we analyzed the association of seven single nucleotide polymorphisms (SNPs), rs846910, rs1205, rs1501299, rs1801282, rs1800497, rs757110 and rs1136287, with obesity and related metabolic traits in a young Mexican-American cohort of 448 non-related individuals. These seven SNPs were chosen because they have been shown to be associated with obesity or obesity-related phenotypes in previous studies or are located in well-established obesity candidate genes (Table 1). The chosen candidate genes are HSD11B1, CRP, ADIPOQ, PPARG, ANNK1, ABCC8 and SERPINF1. Individuals from this cohort include previously recruited RGV Mexican-American adolescents (7) as well as newly recruited Mexican-American college students. None was from the older Mexican-American Cameron County Hispanic Cohort of RGV (4).

Section snippets

Subjects and Clinical Measurements

A total of 448 volunteers from the Brownsville population (southern Texas) consented to participate. All subjects (and parents for subjects <18 years) provided informed consent prior to participation in the study. Consent was specifically obtained to save identified DNA samples for genetic studies. All studies were approved by the IRBs (UTHSC-Houston and UTB). This study was conducted under the basic principles of the Declaration of Helsinki. Inclusion criteria include Mexican-American

Results

Clinical and anthropometric characteristics are shown in Table 2. The median age of the cohort was 16 years and was composed predominantly of female subjects (65%). Based on median value of BMI, the male population in our study is slightly overweight (BMI 25.4). According to BMI values, 28.3% of the sample population is obese, and 21.3% are overweight. However, a total of 53.1% of the subjects have WC measurements correlated with central obesity and considered a risk factor for MetS.

Discussion and Conclusions

Although 21.3% of the young Mexican-American population evaluated in this study is overweight, only 28.3% are obese as defined by BMI. However, when WC is considered, 53% of the subjects are classified as being centrally obese. These results, as well as results from an earlier study, suggest that WC measurement may be a more effective measurement in young Mexican-Americans to assess obesity and metabolic risk than BMI (7).

Rankinen et al. (2005) summarized obesity and/or obesity-related

Acknowledgments

This work was supported by the intramural Borderplex Council Diabetes/Obesity Research funds awarded to S. Nair. The undergraduate students I. Ortiz and E.K. Sanchez were supported as MBRS RISE scholars by the National Institutes of Health (NIH) 5R25 GM065925-7. Dr. A. Rentfro’s work on the collection of the adolescent clinical data was supported by NIH National Center for Minority Health Disparities P20 MD000170-05.

The authors state that there are no conflicts of interest to disclose.

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