weight & body fat

nutrition

KCTD15

Can This Gene Increase Your Risk of Obesity (KCTD15)?

Written by Carlos Tello, PhD on July 10th, 2020

The KCTD15 gene encodes a protein involved in the development of different cell types, including brain and fat cells. Two variants have been associated with increased obesity rates and BMI in some populations. Read on to learn where your genes stand.

What Is the KCTD15 Gene?

The KCTD15 gene encodes a protein called ‘Potassium channel tetramerization domain-containing protein 15’. Members of the KCTD family contain a domain typically found in potassium channels but are not involved in the transport of this mineral [R].

KCTD15 inhibits the development of a special type of stem cells called ‘neural crests’. Neural crests may give rise to cells of the brain, bones, fatty tissue, and skin in the developing embryo. In line with this, animals with mutated KCTD15 forms had developmental abnormalities [R, R, R, R].

A study in rats showed that KCTD15 is mainly expressed in the hypothalamus and fatty tissues [R].

Scientists believe that KCTD15 influences body fat by regulating proteins involved in the development of fatty cells from neural crests. Interestingly, obesity and high-fat diets reduced its expression in animal studies [R, R, R, R, R, R, R, R].

Because KCTD15 contributes to brain cell development and is highly expressed in a brain region involved in eating behavior (the hypothalamus), another possibility is that it influences body weight by regulating food intake. In line with this, flies lacking KCTD15 ate larger meals while those overproducing it ate smaller food amounts but more frequently [R].

The KCTD15 gene encodes a protein that controls the development of stem cells. It may influence body fat through its role in the development of fatty cells and feeding behavior.

KCTD15 Variants in Body Weight

The major ‘G’ variant of rs11084753 was first identified as an obesity risk allele in a study on European descendants. Its association with high BMI and obesity was replicated in American Hispanic women, Norwegian adolescents, and Chinese and British children [R, R, R, R, R].

However, no association with obesity traits was found in some studies on Japanese, Swedish, German, and Emirati adults, and Brazilian and Chinese children [R, R, R, R, R, R].

This variant has also been linked to an increased risk of heart disease in diabetic women but also with reduced risk of colorectal cancer in a multiethnic American population [R, R].

The major ‘G’ variant of the other main polymorphism, rs29941, was associated with obesity, high BMI, and waist circumference in Chinese, Japanese, and British adults, and Chinese and American children [R, R, R, R, R, R].

However, the association couldn’t be replicated in some studies on Japanese, Danish, Mexican, and Emirati adults, Czech adolescents, and Mexican and Chinese children [R, R, R, R, R, R, R].

This variant has also been associated with increased insulin resistance in Chinese children and with reduced risk of colorectal cancer in a multiethnic American population [R, R].

How It Works

Unfortunately, none of the studies investigated the effects of these variants on KCTD15 expression or activity. Based on the overall mechanism by which KCTD15 prevents the development of fatty tissues and reduces food intake, we can speculate that the minor alleles encode protein variants with increased activity.

As will be discussed in the following section, KCTD15 variants associated with obesity also increase the preference for dietary fats and carbohydrates, which promotes weight gain [R, R].

Two KCTD15 variants have been associated with increased obesity rates and BMI, although not in all studies.

Your KCTD15 Results for Body Weight

SNP Table

variant	genotype	frequency	risk allele
rs11084753
rs29941

SNP Summary and Table

Primary SNP:

KCTD15 rs11084753

‘G’ = associated with increased BMI and obesity rates.
‘A’ = associated with reduced obesity rates.
45% of the world population carries one copy of each allele.
The ‘A’ variant is especially rare in European descendants (only 9% of ‘AA’) but very common in people with an East Asian background (47% of ‘AA’).

Other Important SNPs:

KCTD15 rs29941

‘G’ = associated with increased BMI, waist circumference, and obesity rates.
‘A’ = associated with reduced obesity rates.
42% of the world population only carries the ‘G’ allele.
‘A’ is even less frequent in people of European and African ancestry but more common than ‘G’ in East Asian descendants.

Recommendations

Diet

Low-Saturated Fat, Low-Carbohydrate Diets

In a study on pregnant women, those with a copy of the ‘G’ variant at rs11084753 gained more weight than non-carriers, especially if they consumed a high-fat diet [R].

Chinese children carrying this variant showed increased preference for salty foods, which may cause an increased intake of sugar-sweetened soft drinks to curb thirst. In addition, high salt intake may contribute to obesity by causing water retention and reducing fat burning [R].

A barely-investigated KCTD15 polymorphism (rs368794, whose major variant is practically always inherited with the risk variant of rs11084753) was associated with an increased intake of saturated fats and carbohydrates, possibly explaining the contribution of this gene to obesity [R].

People with risk KCTD15 variants should be especially mindful of the composition of their diet to prevent obesity.

Some research suggests that getting more calories from proteins (as opposed to either carbohydrates or fat) may support weight loss, metabolism, and satiety. High-protein diets appeared to increase fat burning and weight loss and reduce appetite in a handful of human studies [R, R, R].

In a clinical trial on 119 overweight people, a low-carbohydrate ketogenic diet was as effective as a low-fat diet for weight loss but had the advantages that it reduced appetite and negative affect. A meta-analysis of 13 studies and over 1,500 people concluded that low-carbohydrate ketogenic diets are more effective than low-fat diets for losing weight [R, R].

Eating a diet low in saturated fats and carbohydrates helps lose weight. Some KCTD15 variants are associated with increased intake of fats and carbohydrates, possibly explaining their contribution to obesity.

Carlos Tello

PhD

Carlos received his PhD and MS from the Universidad de Sevilla.

Carlos spent 8 years in the laboratory investigating mineral transport in plants. He then started working as a freelancer, mainly in science writing, editing, and consulting. Carlos is passionate about learning the mechanisms behind biological processes and communicating science to both academic and lay audiences. He strongly believes that scientific literacy is crucial to maintaining a healthy lifestyle and avoiding falling for scams.

Disclaimer

The information on this website has not been evaluated by the Food & Drug Administration or any other official medical body. This information is presented for educational purposes only, and may not be used to diagnose or treat any illness or disease.

Also keep in mind that the “Risk Score” presented in this post is based only on a select number of SNPs, and therefore only represents a small portion of your total risk as an individual. Furthermore, these analyses are based primarily on associational studies, which do not necessarily imply causation. Finally, many other (non-genetic) factors can also play a significant role in the development of a disease or health condition — therefore, carrying any of the risk-associated genotypes discussed in this post does not necessarily mean you are at increased risk of developing a major health condition.

Always consult your doctor before acting on any information or recommendations discussed in this post — especially if you are pregnant, nursing, taking medication, or have been officially diagnosed with a medical condition.

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Content

What Is the KCTD15 Gene? KCTD15 Variants in Body Weight Your KCTD15 Results for Body Weight

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