LTF Gene Variants May Increase Risk of Metabolic Syndrome in Obese Individuals, Study Says

Patricia Inacio PhD avatar

by Patricia Inacio PhD |

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Mrp4 gene and obesity

Certain variants in the lactoferrin (LTF) and lactoferrin receptor-related genes may increase the risk for metabolic syndrome in obese people, a study suggests.

The study, “Metabolic Health in Obese Subjects—Is There a Link to Lactoferrin and Lactoferrin Receptor-Related Gene Polymorphisms?,” was published in the journal Nutrients.

Obesity can lead to changes in metabolism that cause health and quality-of-life decline. It is well-established that excessive body weight is linked to insulin resistance and type 2 diabetes, as well as cardiovascular diseases, such as hypertension (high blood pressure) and dyslipidemia (abnormal fat levels in the blood).

Estimates show that about 75% of obese people are metabolically unhealthy. Early detection of people at high risk for metabolic abnormalities would allow timely measures to prevent and perhaps even halt metabolic deregulation.

Previous research has suggested that LTF and lactoferrin receptor-related genes may play an important role in the development of metabolic syndrome in obese people. Lactoferrin is an iron-binding protein that plays a major role in the innate immune system.

Now, researchers at the Poznan University of Medical Sciences, in Poland, investigated whether the prevalence of variations in such genes are linked to the metabolic state of people with obesity.

The study enrolled 452 obese subjects (79.4% women) with a median age of 61. Median body mass index (BMI) was 31.73 kg/m2 and median waist circumference (WC) was 104.5 cm. Obesity was defined by a BMI equal or higher than 30 kilograms per square meter (kg/m2) or a WC of at least 80 cm for women and 94 cm for men.

Participants were divided into two groups: metabolically healthy obesity (MHO, 161 participants); and metabolically unhealthy obesity (MUHO, 291 participants).

High blood pressure, anti-hypertension medication, high blood levels of triglycerides, low levels of HDL (“good”) cholesterol, high glucose levels during fasting and/or a prior diagnosis of type 2 diabetes determined whether a participant was classified as MHO or MUHO. Specifically, people had MUHO if positive for at least two of these factors and MHO if they had none or one.

Participants classified as MHO were younger and had significantly lower WC, as well as lower triglycerides, total cholesterol and glucose levels than people with MUHO. Blood pressure also was lower and HDL cholesterol levels were higher in the MHO group.

The researchers observed that small mutations, known as single nucleotide polymorphisms (SNPs), in the LTF gene were found at different frequencies between the MUHO and MHO groups.

In particular, they found that a specific SNP in the LTF gene (called rs2239692) was linked to a significant decrease in the risk for developing metabolic syndrome in people with obesity.

Other LTF gene variants also were associated with differences in body weight and WC.

By calculating the association of each variant with clinical metabolic parameters, the researchers were able to define a set of SNPs that were protective of metabolic syndrome while others were risk factors.

In the MUHO group, participants with at least two protective SNPs had significantly lower body weight (84.9 vs. 87.1 kg), reduced WC — 104 vs. 106.5 cm — and lower diastolic blood pressure (86 vs. 88 mmHg).

Those with at least two risk SNPs had lower levels of HDL cholesterol compared to people with less than two risk SNPs when considering all participants (55 vs. 58 mg/dL) and the MHO group specifically 59 vs. 65 mg/dL.

Overall, this study suggests that “selected lactoferrin and lactoferrin receptor-related gene variants may be associated with the prevalence of metabolically healthy or metabolically unhealthy obesity,” the scientists wrote.

“However, future studies are needed to understand how the analysed polymorphisms might impact the development of metabolic abnormalities in obese subjects,” they concluded.

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