VDR Gene Variations Increase Obesity Risk in Type 2 Diabetes, Study Finds

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by Patricia Inacio PhD |

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Certain variations in the DNA sequence of the vitamin D receptor (VDR) gene increase the risk for obesity in patients with type 2 diabetes, a South Korean study reports.

The study, “The Associations Between Vitamin D Receptor BsmI and ApaI Polymorphisms and Obesity in Korean Patients with Type 2 Diabetes Mellitus,” was published in the journal Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy.

Obesity is linked with a significantly higher risk of developing other diseases, such as diabetes mellitus, high blood pressure (hypertension), altered levels of lipids (dyslipidemia), and heart disease. While environmental factors play a role in obesity incidence, 40–70% of obesity cases have an underlying genetic cause.

Vitamin D and the VDR receptor play a key role in regulating the endocrine (hormone-related) system, as well as in metabolic and immune responses. The VDR gene is active in adipocytes (fat cells) and beta cells, which are the cells in the pancreas responsible for producing insulin. As a result, variations in the sequence of the VDR gene can have significant effects on health.

More than 470 DNA small variations, also called polymorphisms, have been identified in the VDR gene. While these variations have been linked with the risk for obesity, results to date have been inconsistent.

In this study, a group of researchers in South Korea evaluated the link between certain VDR gene polymorphisms and obesity in people with type 2 diabetes, a disorder whose risk increases in obese individuals.

Specifically, they looked at two polymorphisms, called BsmI and ApaI in the VDR gene. The genetic analysis was carried out in white blood cells.

Cells have two copies of each gene, or alleles. One allele is usually dominant, meaning that its information is the one “read” over the recessive allele. In genetics nomenclature, a dominant trait of BsmI present in both alleles in translated as BB, while a recessive trait is bb. When both are present, it is called Bb. The same principle was applied for ApaI, but this time called AA, aa, or Aa.

In total, 506 participants with diabetes type 2 — 266 men and 240 women, mean age 62.6 — were included in this study. The mean body mass index (a measure of body fat) was 25.1 kg per square meter (kg/m2). Participants were classified as obese if BMI was higher than 25 kg/m2. Accordingly, 236 patients were classified as obese, as their mean BMI was 27.9 kg/m2, and the 270 remaining participants had normal weight (mean BMI 22.7 kg/m2).

The analysis of BsmI showed that the majority of participants (87.7%) carried the bb genotype. In turn, the Bb genotype was found in 10.3% patients and BB in 2.0%.

In the case of ApaI, the aa genotype was seen in 48.6% participants, followed by 46.8% with Aa, and 4.5% with AA.

The bb polymorphism was linked with a significantly higher prevalence of obesity (48.4%) compared to BB and Bb combined (33.9%). Mean BMI was 25.2 kg/m2 in participants with the bb genotype (genetic profile) and 24.1 kg/m2 in those with BB or Bb.

The presence of the b allele was significantly associated with obesity, with researchers estimating that this genotype increased by 2.13 times the likelihood of developing obesity.

“We found that patients with T2DM [type 2 diabetes mellitus] carrying the bb genotype of VDR BsmI polymorphism were associated with higher BMI and increased risk of obesity than the BB or Bb genotypes,”  the researchers wrote.

The analysis of ApaI showed that participants with an “a” allele (Aa or aa) had a significantly higher prevalence of obesity (47.6%) compared to those with AA (26.1%). The presence of the “a” allele was linked with a 2.71 times higher risk for obesity.

Female sex, hypertension and dyslipidemia were among the risk factors for obesity.

Overall, “the present study demonstrated that BsmI and ApaI polymorphisms of the VDR gene were associated with obesity in Korean patients with T2DM,” the researchers wrote.

“Further studies with larger multiethnic cohorts [groups] and experimental models are required to validate our results,” they concluded.

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