New Gene Variant Explains Proclivity for Alcohol

The genetic blueprint of all forms of life on the earth is composed of deoxyribonucleic acid
(DNA). The double helix shaped DNA consists of the instructions that every human needs to
develop, live and reproduce. The difference in its sequence and structure is the reason behind
all kinds of diversities. In fact, it is also responsible for those minor and subtle differences that
make one person different from another. For many decades now, scientists believe that
understanding the human genome is the gateway to the mysterious world of the human
mind.
The Human Genome
Project has mapped
out 20,000 to 25,000
genes in the human
body. Based on the
arrangement of genes,
a person may be
resilient to certain
physical and mental
disorders or prone to
the onset of physical
and mental
conditions. Scientists
world over continue to
conduct advanced
researches to have
more information on
genetics. An ongoing
study led to a revelation recently pertaining to the discovery of a gene variant that explains
how some people gravitate to alcohol more than others.
New gene variant may explain maladaptive drinking patterns
In the study, published in the Proceedings of the National Academy of Sciences (PNAS),
researchers found a gene variant known as -Klotho (KLB) that is associated with the lower
rates of alcohol consumption among the people of European descent. The study, led by David
Mangelsdorf, Ph.D., Chair of Pharmacology, University of Texas Southwestern Medical
Center, entailed the DNA assessment of over 100,000 people. It was discovered that KLB, a
receptor in the brain that encrypts and attaches to FGF21 (for fibroblast growth factor 21), a
hormone produced by the liver, together producing a gut-brain communication structure.
In previous studies, Mangelsdorf had found that FGF21 is a major component in regulating
the craving for sugar. The studies, which included mice and monkeys, exhibited the release of
this hormone whenever there is a high sugar intake. By affixing to -Klotho receptors, FGF21
suppresses the need to consume more sweets. With the metabolization of ethanol, a sugar-
like molecule, commonly known as acetate, triggers the release of FGF21.

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Therefore, the cravings for drinking depends on the same gut-brain pathway as in the case of
sweets. In this rat-based study, Mangelsdorf and his team tried finding out how the gut-brain
communication channels could influence alcohol intake. To follow through, the mice were
divided into two groups, including one with their -Klotho inhibited and another group of
regular mice. The researchers tried to determine the amount of alcohol the mice drank by
comparing with the option of water, especially when offered the option of two bottles.
The results are as follows:
Mice with their -Klotho knocked out displayed a greater preference for alcohol,
which significantly changed when they were given FGF21.
Regular mice who were administered FGF21 displayed a marked decrease in drinking.
Discovery of a new gene variant labelled rs11940694, which can affect the way -
Klotho and FGF21 interact.
Both groups of mice also underwent behavioral examinations, but the investigators
found no difference in fear or anxiety levels, thereby concluding that the lack of -
Klotho in mice does not lead to drinking to relieve stress and anxiety.
The findings of the study that explains the genetic nuances contributing to indulgence in
drinking are particularly relevant in the case of episodic heavy drinking. Some people
indulging in heavy drinking rely on the breakdown of acetate rather than glucose in alcohol.
As a result, the presence of the KLB gene variant in such individuals can suppress the efficacy
of the FGF21 hormone, thereby resulting in more drinking.
Help is at hand
Although the genes play a crucial role in increasing cravings for alcohol, external factors like
ones environment, personality, traumatic experiences and other stressors, also lead to heavy
drinking. Alcohol has the ability to rewire the brain, which can trigger various social, personal
and health consequences. Therefore, one is recommended to seek intervention at the earliest
to avoid the problem from cascading.
If you or your loved one is battling alcohol addiction, it is imperative to seek help. The Arizona
Alcohol Addiction Helpline assists in connecting to the best alcohol addiction treatment in
Arizona. Call at the 24/7 helpline number 866-671-1510 to know more about the alcohol
addiction treatment centers in Arizona.

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