Genetic factors, such as the mitochondrial DNA (mtDNA) T16189C polymorphism, have been associated with metabolic syndrome (MetS), but this association has not been studied in Mexico to date. The aim of the present study was to determine whether this polymorphism contributes to MetS in the Mexican population. We recruited 100 unrelated volunteer subjects who were divided into 2 groups: with MetS (MetS group) and without MetS (control group). All subjects were genotyped for the mtDNA T16189C polymorphism by polymerase chain reaction and sequencing. The mitochondrial T16189C polymorphism was detected in 24 (24%) of 100 subjects analyzed. The frequency of the mtDNA T16189C polymorphism was higher in the MetS group with 21 (32.3%) of 65 testing positive compared to 3 (8.5%) of 35 in the control group, indicating that this polymorphism is a probable risk factor for MetS in the Mexican population (odds ratio 5.0909, 95% CI 1.3977–18.5424,
Metabolic syndrome (MetS) is a metabolic disorder that affects approximately 45% of the Mexican population according to the National Health and Nutrition Survey of 2012 [
Genetic factors, including the mitochondrial DNA (mtDNA) T16189C polymorphism, have been associated with MetS and type 2 diabetes mellitus (DM2) [
T to C substitution at mtDNA position 16189, within the regulatory displacement loop (D-loop), produces an uninterrupted polycytosine stretch (poly-C) which interferes with mtDNA replication [
In Mexico, the association between MetS and the mtDNA T16189C polymorphism has not yet been studied. The aim of the present study was to determine whether this polymorphism contributes to MetS in the Mexican population.
Our study was conducted in México City in the “Hospital Central Militar” of the National Defense Ministry of México. We recruited 100 unrelated volunteer subjects, who were divided into 2 groups: with MetS (MetS group) and without MetS (control group). The control group consisted of 35 healthy subjects, and the MetS group had 65 subjects diagnosed with MetS defined by the guidelines of the National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATP III) most frequently used in the world and in medical practices [
Genomic DNA extracted with a DNeasy Blood and Tissue kit (Qiagen) from oral brushing was used as a template. Polymorphism detection was performed by polymerase chain reaction (PCR) with the specific primers 5
Measurements of biochemical parameters were performed with an ADVIA 1800 Chemistry System (Siemens) from serum.
All clinical data and biochemical parameters were expressed as the mean ± standard deviation (SD), and the comparison of variables between experimental groups was performed by Student’s
Our study included 100 subjects, and the mean age of the participants was 58.35 ± 10.0; 78% of the study subjects were female, and only 22% were males. In this study, more than half of the study subjects (74%) are overweight (39%) and obese (35%). Overweight was present about 40% in both groups, and obesity was present in about 23% in the control group and 42% in the Mets group. The clinical characteristics of the study population are summarized in Table
Characteristics of study population.
Characteristic | Control group | MetS group | |
---|---|---|---|
Mean ± SD | Mean ± SD | ||
35 | 65 | ||
Male/female | 8/27 | 14/51 | |
Age (y) | 58.40 ± 11.44 | 58.08 ± 9.24 | 0.879 |
Waist circumference (cm) | 93.31 ± 9.22 | 99.78 ± 9.32 | 0.001 |
Body mass index (kg/m2) | 26.41 ± 4.27 | 29.21 ± 5.07 | 0.006 |
Systolic blood pressure (mmHg) | 107.83 ± 16.19 | 124.35 ± 18.37 | <0.001 |
Diastolic blood pressure (mmHg) | 70.20 ± 8.69 | 77.15 ± 8.29 | <0.001 |
Glucose (mg/dl) | 112.06 ± 63.53 | 135.29 ± 55.90 | 0.062 |
Triglycerides (mg/dl) | 118.23 ± 43.56 | 168.37 ± 97.67 | 0.005 |
HDL-cholesterol (mg/dl) | 51.12 ± 12.12 | 41.52 ± 8.72 | <0.001 |
HBA1C (%) | 6.55 ± 1.90 | 7.98 ± 2.40 | 0.003 |
Presence of NCEP/ATPIII criteria in study population.
Criteria | Control group | MetS group | |
---|---|---|---|
Mean ± SD | Mean ± SD | ||
Waist circumference | |||
>102 cm (males) |
18/35 (51.43) | 54/65 (83.08) | 0.0004 |
HDL-C mg/dl | |||
<40 (males) |
11/35 (31.43) | 54/65 (83.07) | <0.0001 |
Triglycerides > 150 mg/dl | 6/35 (17.14) | 30/65 (46.15) | 0.002 |
Blood pressure > 130/85 mmHg | 1/35 (2.86) | 29/65 (44.61) | <0.0001 |
Glucose > 110 mg/dl | 9/35 (25.71) | 31/65 (47.69) | <0.0152 |
The mtDNA T16189C polymorphism was detected in 24 (24%) of 100 subjects analyzed. The frequency of the mitochondrial T16189C polymorphism was higher in the MetS group, with 21 (32.3%) of 65 testing positive compared to 3 (8.5%) of 35 in the control group, suggesting that the polymorphism is associated with MetS (odds ratio 5.0909, 95% CI 1.3977–18.5424,
Detection of mitochondrial DNA (mtDNA) T16189 C polymorphism (a) 3% agarose gel (1) molecular marker, (2) no template PCR control, and (3–9) amplicons obtained from representative samples. (b, c) Wild-type sequence and mtDNA T16189C polymorphism, respectively. The arrows indicated the variants detected.
Characteristics of study population with and without mtDNA T16189C polymorphism.
Parameter | mtDNA T16189C polymorphism | ||
---|---|---|---|
T | C | ||
76 | 24 | ||
Male/female | 15/61 | 7/17 | |
Age (y) | 58.96 ± 10.69 | 55.75 ± 7.09 | 0.172 |
Waist circumference (cm) | 97.38 ± 9.75 | 97.94 ± 9.90 | 0.809 |
BMI (kg/m2) | 28.38 ± 5.01 | 27.77 ± 4.94 | 0.601 |
Systolic blood pressure (mmHg) | 117.59 ± 17.92 | 121.67 ± 23.16 | 0.369 |
Diastolic blood pressure (mmHg) | 74.50 ± 9.13 | 75.42 ± 8.84 | 0.667 |
Glycemia (mg/dl) | 119.76 ± 54.37 | 150.58 ± 69.29 | 0.026 |
Triglycerides (mg/dl) | 137.97 ± 62.17 | 191.50 ± 130.24 | 0.007 |
HDL-C (mg/dl) | 46.88 ± 11.32 | 38.55 ± 6.86 | <0.001 |
HBA1C (%) | 7.15 ± 2.06 | 8.52 ± 2.84 | 0.012 |
In this work, we explored the mtDNA T16189C polymorphism in populations of subjects with or without MetS diagnosed based on NCEP/ATP III criteria. According to this definition, MetS is diagnosed if three of the five features are present; in our MetS group, 23% presented 4 o 5 features, which demonstrate an adequate grouping according to the NCEP/ATP III criteria. The study groups were homogeneous in terms of age and sex, which is very important because our population was of age > 40 years, and MetS has an increased risk in old age [
The mtDNA T16189C polymorphism explored here was detected in 25% of the study population, similar to the reported frequency in southern Brazil (21.15%) [
We observed that the frequency of the mtDNA T16189C polymorphism was higher in the MetS group, with 21 (32.3%) of 65 testing positive compared to 3 (8.5%) of 35 in the control group, suggesting that this polymorphism is associated with MetS in the Mexican population as previously reported for other populations [
Overweight and obesity are highly prevalent in the Mexican population. In addition, 25.2% of adults with Mets have a diagnosis of obesity, which is recognized as the main risk factor for MetS [
In conclusion, our results indicate that the T16189C polymorphism is a possible risk factor for MetS in the Mexican population, but larger sample sizes are necessary to confirm the role of the susceptibility variant described in this report.
The authors declare that they have no conflicts of interest.
This work was performed in the Laboratorio Multidisciplinario de Investigación, Escuela Militar de Graduados de Sanidad, UDEFA.