Gene Linked to Obesity, Diabetes Seen to Vary with Ethnicity in Study

Iqra Mumal, MSc avatar

by Iqra Mumal, MSc |

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Mutations in the gene coding for a protein called adiponectin are associated with a higher likelihood of type 2 diabetes  and obesity. However, this relationship varies with ethnicity, a study in India found.

The study, “A genetic analysis identifies a haplotype at adiponectin locus: Association with obesity and type 2 diabetes,” was published in the journal Scientific Reports.

Metabolic syndrome — which includes obesity and type 2 diabetes — is a growing public health problem worldwide.

But their prevalence differs based on ethnicity. A previous report showed that — along with genetic susceptibility — migration, nutrition, and lifestyle are the main factors in rising cases of obesity among South Asians.

Obesity and diabetes are intimately linked. Studies have shown that excessive adipose (fat) tissue is a major driver of type 2 diabetes.

Adiponectin, a protein found in adipose tissue, is a regulator of metabolism. Mutations in the adiponectin gene (ADIPOQ) are strongly associated with obesity, diabetes, and altered levels of lipids (fat molecules).

Adiponectin circulates in the blood on three forms of different molecular weight, or size. Notably, the ratio of high molecular weight adiponectin to total adiponectin strongly correlates with high glucose levels.

Genome wide association studies of the ADIPOQ gene identified a relationship between several single nucleotide polymorphisms (SNPs) — changes in a single nucleotide, the building block of DNA — and metabolic syndrome.

Again, significant variation among different ethnic groups has been reported.

Researchers in India investigated how four SNPs in the ADIPOQ gene — known as rs266729, rs17846866, rs2241766 and rs1501299 — associate with type 2 diabetes.

They also assessed whether people with different SNPs would have different levels of glucose, lipids, and body mass index (BMI).

As the Indian population is ethnically diverse, the scientists studied two different groups — one from the state of Gujarat in western India, and another from the northern territories of Jammu and Kashmir.

In total, the study included 475 diabetic patients and 493 healthy people serving as controls from Gujarat, and 507 patients and 300 controls from Jammu and Kashmir. All were between 30 and 67 years old.

Among people from Gujarat, the frequency of the rs17846866 and rs1501299 mutations were up to 2.3 times higher in diabetics than age and sex-matched people without this disease.

Among those from Jammu and Kashmir, only the rs266729 mutation was associated with diabetes, as it was 1.3 times more frequent in patients than in controls.

In the Gujarat group, only one of the four ADIPOQ gene haplotypes (genetic sequences) associated with diabetes was also linked to obesity.

Researchers also found a significant reduction in ADIPOQ gene expression (conversion of DNA to RNA) in diabetic patients from Gujarat compared to matched controls. However,  no significant relationship between RNA levels of ADIPOQ and the four studied SNPs was seen.

In line with previous studies, the ratio of high molecular weight adiponectin to total adiponectin was significantly lower in people with diabetes compared to healthy people. This difference was even greater in people with both diabetes and obesity.

In the Gujarat group only, researchers found that the rs1501299 and rs17846866 mutations were associated with increased fasting blood glucose, BMI, triglycerides (fat), and total cholesterol levels.

“We may conclude that adiponectin gene is associated with T2D [type 2 diabetes], nonetheless variation in the susceptibility loci [spots] within the gene depends on ethnic variation among different populations,” the investigators wrote.

“Reduced HMW [high molecular weight] adiponectin, in the backdrop of obesity and ADIPOQ genetic variants might alter metabolic profile posing risk towards T2D,” they added.

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