Are Plastics More Dangerous For You? (UGT1A1)

The UGT1A1 gene encodes an enzyme called UGT (short for UDP-glucuronosyltransferase). This enzyme is responsible for performing a chemical reaction called glucuronidation, which is an important step in the body’s detox process [R].

Genetic variations in UGT1A1 can impair your body’s ability to clear out harmful substances, which may lead to liver disorders, a dangerous buildup of drug compounds, and even cancer [R, R].

The UGT1A1 gene is responsible for encoding an enzyme called UGT, which plays an important role in the body’s detox process.

How Does UGT Help You Detox?

The UGT enzyme performs a reaction called glucuronidation, which involves adding a compound called glucuronic acid to different substances in the body. This addition helps neutralize harmful toxins and prepares them for excretion out of the body [R].

Some important targets of UGT include:

• BPA plastics [R]
• Bilirubin, a waste product from the breakdown of red blood cells [R]
• Steroid hormones [R]
• Medications: up to 15% of all FDA-approved drugs according to some estimates [R]

The UGT enzyme neutralizes harmful compounds, like BPA plastics, bilirubin, and drugs, so they can be excreted out of the body.

Certain genetic variations in UGT1A1 reduce the enzymatic activity of UGT, which impairs the body’s ability to detox and results in a buildup of toxic substances in the body. The normal version of UGT1A1 (the one with normal detox activity) is called UGT1A1*1, or the “wild” type allele [R].

One of the most important and well-studied genetic variants is UGT1A1*28. This variant causes an “insertion” mutation, which means it adds an extra ‘TA’ into the gene where there should be none. According to some reports, UGT1A1*28 causes a 70% reduction in enzyme activity [R].

Other variants include UGT1A1*6 and UGT1A1*27, which also lower enzyme activity, leading to a reduced ability to detox. All of these variations in UGT1A1 can lead to toxicity disorders, which we’ll detail in the following sections [R].

Genetic variations of UGT1A1, which include UGT1A1*28, UGT1A1*6, UGT1A1*27, lower the activity of the UGT enzyme, which leads to a buildup of toxic substances in the body.

BPA Plastic Toxicity

BPA, short for bisphenol-A, is a chemical compound found in many types of plastic. A buildup of BPA in the body is linked to several disorders, including cancer, heart disease, and thyroid dysfunction. Removal of BPA is primarily the responsibility of UGT; genetic variations in UGT1A1 can lower the body’s ability to detox BPA-based plastics [R].

A small study of 15 people found that those with UGT1A1*28 remove BPAs in the breast tissue 10 times more slowly compared to those without the allele. This finding has important clinical implications: BPA exposure has been connected to breast cancer in several studies [R].

Genetic variations like UGT1A1*28 can impair the body’s ability to remove BPA, which some researchers believe can lead to an increased risk of breast cancer.

Drug Toxicity

According to some estimates, the UGT enzyme is responsible for metabolizing and clearing 15% of all FDA-approved drugs. Certain genetic variations of UGT1A1 can impair the body’s ability to remove these drugs, which can worsen side effects and cause toxicities [R, R].

The most researched drug interaction with UGT1A1 is irinotecan, a drug used to treat colon and lung cancer. Studies show that people with UGT1A1*28 who take this drug are much more likely to experience neutropenia, a dangerous reduction in white blood cell count. The FDA recommends that people with UGT1A1*28 should start at a lower dose to reduce toxicity [R, R].

Other drugs with serious interactions with UGT1A1 variants include [R]:

• Raloxifene, used to treat osteoporosis and prevent breast cancer
• Raltegravir, used to treat HIV
• Indinavir, used to treat HIV
• Atazanavir, used to treat HIV
• Sorafenib, used to treat various cancers

People with the UGT1A1*28 variant may experience more side effects with certain drugs and may need a lower starting dose.

Bilirubin Toxicity

Bilirubin is a waste product that your body naturally produces during the breakdown of old red blood cells. The UGT in your liver will then process bilirubin so that it can be excreted either through urine or feces [R].

Genetic variations of UGT1A1 can reduce or completely eliminate the body’s ability to remove bilirubin, causing a dangerous buildup. This can lead to disorders like Gilbert’s syndrome or Crigler–Najjar syndrome, which can cause yellowing of the skin, fatigue, loss of appetite, and even more serious symptoms in children [R, R].

Those with genetic variations in UGT1A1 may have difficulty detoxing bilirubin, which may lead to disorders like Gilbert’s syndrome or Crigler–Najjar syndrome.

Primary SNP: 

UGT1A1*28 is one of the primary genetic variants responsible for reduced detox ability. This variant adds a ‘TA’ allele where they should be none. These SNPs normally have no allele; gene reports will sometimes use ‘D’ (short for deletion) to represent the absence of an allele.

The ‘TA’ addition increases your risk for toxicity, which is sometimes represented as ‘I’ (short for insertion).

UGT1A1 rs34983651

• ‘D’ (short for deletion, represents an absence of the extra ‘TA’) = Normal detox function
• ‘I’ or ‘TA’ insertion = Increases your risk for toxicity
• UGT1A1*28 occurs in 26-31% of Caucasians, but only 9-16% of Asian populations

Other Important SNPs:

UGT1A1 rs4148323

• ‘G’ = Normal detox function
• ‘A’ = Increases your risk for toxicity
• About 6% of people have the risky ‘AA’ genotype

UGT1A1 rs6742078

• ‘G’ = Normal detox function
• ‘T’ = Increases your risk for toxicity
• About 56% of people have the risky ‘TT’ genotype