Variant in Vitamin D Receptor Gene Linked to Higher Obesity Risk, Study Suggests
People with a specific variant in the gene coding for the vitamin D receptor have almost twice the risk of being obese, a study suggests.
The study, “New evidence for associations between vitamin D receptor polymorphism and obesity: case-control and family-based studies,” was published in the Journal of Human Genetics.
The incidence of obesity has been rapidly increasing over the last few decades. Currently, more than 30% of adults worldwide are considered obese.
Several lines of evidence suggest that vitamin D deficiency is associated with obesity. Because the active form of vitamin D — identified as 1,25 (OH)2D — suppresses adipogenesis, or the development of fat cells, researchers believe that lacking vitamin D could increase a person’s likelihood of becoming obese.
Single nucleotide polymorphisms (SNPs) are variations in a single nucleotide, the building blocks of DNA. Case-control studies have shown that SNPs within the VDR gene, which provides instructions to make the vitamin D receptor, are associated with obesity. However, such assessments — which compare patients who have a disease or condition with unaffected participants — may lead to false positive results, the team from China said.
Aiming to further explore such associations, the researchers used both a case-control study and a different approach — a family-based study. Using this family-based approach may limit the risk of false positive findings, the team said.
First, the scientists investigated the link between SNPs and obesity using a case-control study with 688 individuals. Next, they tested the association of validated SNPs with body mass index (BMI) in a family-based study that included 419 pedigrees, or family trees, and 1,560 individuals in Wuzhi County, in Henan Province, China. Then, the association between SNPs and BMI was further validated in siblings.
Results from the case-control study suggested that a specific SNP known as rs3847987 is associated with a greater risk for obesity, identified as having a BMI of 28 kg/m2 or greater. In contrast to the normal DNA sequence — which includes two cytosine nucleotides together (CC) — people with rs3847987 have either an adenine nucleotide coupled with cytosine (AC) or two adenine residues (AA).
Compared with the reference CC sequence, having an AC pair of nucleotides was linked with a nearly two-fold increased likelihood of becoming obese.
The findings from the family-based test supported these results. Among the families in the study, 29 had siblings with CC and AC sequences, two had siblings with AA and CC genetic profiles, and 10 had siblings with AA and AC nucleotides in rs3847987. These families were then part of the study examining siblings.
Siblings with the AC sequence in rs3847987 showed significantly higher BMI compared with family members with CC. In contrast, no significant association between the AA sequence and obesity was observed.
“Therefore, it could be concluded that VDR genetic polymorphism (rs3847987) may be associated with obesity,” the scientists said.
“The function of rs3847987 and its related mechanism should be investigated in further study,” they added.
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