Egyptian Study Links Obesity Risk to Gene Variants Associated With Type 2 Diabetes

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by Joana Carvalho |

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Two gene variants normally associated with type 2 diabetes risk are also linked to obesity in an Egyptian population, a study has found.

The study, “Evaluation of genetic susceptibility of six type II diabetes genome-wide association studies loci for obesity,” was published in the journal Meta Gene.

Obesity is thought to result from a combination of genetic, environmental, and lifestyle factors. A recent genome-wide association study (GWAS) reported that 941 single nucleotide polymorphisms (SNPs) are associated with changes in body mass index (BMI).

SNPs are variations in a single nucleotide, the building blocks of DNA, in the sequence of a gene. GWAS are studies that scan the genome (all genes present in human DNA) looking for specific alterations found more frequently in people with a particular disease.

In the new study, investigators in Egypt performed a GWAS to assess if six SNPs previously associated with a higher risk of type 2 diabetes — rs3923113 in the GRB14 gene, rs16861329 in ST6GAL1, rs1802295 in VPS26A, rs7178572 in HMG20A, rs2028299 in AP3S2, and rs4812829 in HNF4A — could also be linked to a higher risk of obesity and fat gain in an Egyptian population.

The study included data from 456 participants, including 300 obese individuals selected from the Obesity Surgery Unit at Yousri Gohar Hospital, and 156 healthy individuals, who served as sex- and age-matched controls.

Blood samples collected from all study participants after 12 hours of fasting were used to isolate DNA for genetic analyses.

When the researchers assessed the frequency of each of the six genetic variants, they found that three of the mutations (rs3923113, rs1802295, and rs4812829) were significantly different between the groups when a model of dominant inheritance was used in the analyses.

In turn, when a recessive inheritance model was used, significant differences were found in only two SNPs — rs2028299 and rs4812829.

In dominant inheritance, only one copy of a variant is necessary to increase the risk of inheriting a specific disease, whereas in recessive inheritance, two copies of the mutation are required to produce the same effect. Each gene has two copies, one inherited from each parent.

According to two or more inheritance models, two variants — rs2028299 and rs4812829 — were more common in the obese participants than in the controls.

“SNPs rs2028299 (AP3S2) and rs4812829 (HNF4A) are significantly associated with obesity,” the researchers wrote.

Age, weight, and BMI were associated with specific changes in rs2028299, while weight correlated with changes in rs4812829.

In two SNPs, rs16861329 and rs7178572, the investigators found no differences in frequency between obese and healthy individuals, regardless of the inheritance model they used.

“Future studies with larger sample sizes are recommended not only to explain the effect of the already known SNPs, but also to discover other new variants concerned with affecting this group of related health problems, namely hypertension, diabetes and obesity,” the team wrote.

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