Gout: The Other Gene That Affects Urate Levels and Gout Development

The ABCG2 gene belongs to a group of genes called the ATP-binding cassette family; genes in this family provide instructions for making proteins that transport molecules across cell membranes. In the intestines, the ABCG2 protein helps release (secrete) a substance called urate into the urine. Urate is a byproduct of certain normal biochemical reactions in the body. In the bloodstream it acts as an antioxidant, protecting cells from the damaging effects of unstable molecules called free radicals. Urate levels are regulated by the kidneys and, to a lesser extent, by the intestines.

The ABCG2 protein also transports certain drugs out of cells. For example, this protein clears some chemotherapy drugs from organs and tissues. Transport of these drugs allows them to have their intended effects and be eliminated from the body.

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Gout: Genes that Affect Urate Levels and Gout Development

The SLC2A9 gene provides instructions for making a protein called glucose transporter 9 (GLUT9). This protein is found mainly in the kidneys, specifically in structures called proximal tubules. These structures help to reabsorb needed nutrients, water, and other materials into the blood and excrete unneeded substances into the urine. Within the proximal tubules, the GLUT9 protein helps reabsorb or excrete a substance called urate. Urate is a byproduct of certain normal biochemical reactions in the body. In the bloodstream it acts as an antioxidant, protecting cells from the damaging effects of unstable molecules called free radicals. When more urate is needed in the body, the GLUT9 protein helps reabsorb it into the bloodstream. Most urate that is filtered through the kidneys is reabsorbed into the bloodstream; about 10 percent is released into urine.

The GLUT9 protein also plays a role in reabsorbing and excreting the simple sugar glucose.

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Gout: Genetics or Lifestyle Driven?

Genetic and genetic mutations can certainly play a role in disease, however, poor nutrition and a sedentary lifestyle can greatly increase the risk. Gout is a common condition, but it occurs more frequently in some populations than others. For example, gout occurs in 1 percent of people with Asian ancestry, 3 to 4 percent of people with European ancestry, and 6 to 8 percent of Indigenous (native) Taiwanese peoples and Māori from New Zealand.


In about 15 percent of people with gout, urate accumulates in the kidneys
and forms kidney stones . As the condition worsens, urate crystals can also be deposited under the skin or in other soft tissue, forming a nodule called a tophus (plural: tophi). These tophi often form in the hands, elbows, or feet. Tophi do not typically cause pain, but they can become inflamed, infected, or ooze fluid. Depending on their location, tophi can interfere with movements such as walking or gripping objects.

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Gout and Metabolic Disease: Can Probiotics help?

As we know, many studies have linked Gout with chronic inflammation and obesity.  Both conditions contribute a group of factors that increase the risks of heart disease, stroke, and diabetes – also known as metabolic syndrome.  Metabolic syndrome is a cluster of biochemical and physiological abnormalities affecting an estimated 50 million Americans.

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What can you do to alleviate Gout symptoms?

1) Try to get an accurate diagnosis if possible.

HOWEVER, these suggestions are accurate and helpful with any inflammatory attack and can be followed, regardless of a firm diagnosis. Blood testing can be very misleading. Arthrocentesis, or joint aspiration, is the only secure method of evaluating any crystallized deposits in the joints.

2) Take the right anti-inflammatory medications. Continue reading “What can you do to alleviate Gout symptoms?”

FDA Adds Boxed Warning for Increased Risk of Death with Gout Medicine Uloric (febuxostat)



Uloric (Febuxostat) was FDA approved in 2009 as a means to treat Gout, a form of arthritis. The FDA has since concluded that there is an increased risk of heart-related death and death from all causes from Uloric and now requiring a boxed label warning.

The makers of Uloric (Febuxostat) are also recommending that health care professionals reserve prescribing it only to patients that have failed to achieve relief from Allopurinol or those that were unable to tolerate Allopurinol.

The makers of Uloric, Takeda Pharmaceuticals, were forced to include a “precaution” about possible cardiovascular events in patients at the time of release but has since been updated to the most prominent warning, a boxed warning. Sadly, Takeda Pharmaceuticals was able to manufacture and sell Uloric in the US without any complication warning on the drug’s label for years.

A safety trial was conducted to compare the risks posed by both Allopurinol and Uloric. 15 deaths from heart-related causes per 1,000 patients taking Uloric was observed over a year’s time compared to 11 deaths from heart-related causes per 1,000 treated with Allopurinol. Additionally, 26 deaths from any cause, per 1,000 patients, was observed with Uloric use over that year compared to 22 deaths per 1,000 from Allopurinol. This trial, known as the CARE trial, suggested that Uloric was connected to significantly higher risk for fatal cardiovascular events like heart attacks, strokes, and unstable anginas.

The FDA has been fully aware of these potential complications as early as 2009 and even attempted to minimize the heart problems that Uloric could cause by only approving 40mg and 80mg doses as opposed to the 80mg and 120mg doses that Takeda Pharmaceuticals had requested. Sadly, it took until 2018 for the FDA to require the box label warning based on the results of the postmarket trial that was conducted (CARES).

Uloric (Febuxostat) has also been linked to abnormal liver function. People taking Uloric were shown to have three times higher than normal levels of transaminase. While it remains unlcear as to whether Uloric directly heightens those levels, physicians who prescribe Uloric are supposed to conduct a baseline liver test panel prior to starting Uloric and then continue to monitor for any changes.

Uloric (Febuxostat) has also been linked to severe and potentially fatal allergic reactions. Stevens-Johnson syndrome being one of these observations. Approximately one in 10 people who develop this syndrome fall victim and die from the disease.

The deceptive and faulty marketing that has allowed for years of uninformed use regarding the risk of cardiovascular events has led to numerous lawsuits against Takeda Pharmaceuticals.

Learn More Uloric (Febuxostat)

Learn More About Other Prescription Drugs for Gout

A Careful and Healing Gout Diet

Is it OK to walk with gout?

Medical News Today: It is safe for people to walk with gout. In fact, doing joint friendly activities such as walking can help improve gout-related pain.

Gout is a form of arthritis that usually affects the big toe joint, but it can also affect the lesser toes, ankles, and knees. It normally affects one joint at a time.

People with gout may find it difficult to carry out physical activity, or they may be worried that physical activity will make their gout worse.

This article will examine whether or not it is safe to walk with gout. It will also cover how to manage, treat, and prevent this condition.

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Hyperuricemia as a potential plausible risk factor for periodontitis

Abstract

Author:  Zi-yun Chen,Lu-wen Ye,Li Zhao,Zhao-jia Liang,Ting Yu,Jie Gao

Publication:  Medical Hypotheses

Publisher: Elsevier

Date: April 2020

Elevated blood uric acid (UA) levels have been positively associated with the severity of periodontitis. It thus brings out a hypothesis that hyperuricemia, a pathological elevation of blood UA, might be a risk factor for periodontitis. Namely, periodontitis individuals with Hu might acquire more severe periodontal destruction compared to those without Hu. To support the hypothesis, four aspects of evidences are proposed.

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In-hospital cardiac procedures up for those with gout, rheumatoid arthritis

(HealthDay)—Rates of in-hospital cardiac procedures continued to increase in people with gout and rheumatoid arthritis (RA) from 1998 to 2014, although they decreased for the general population, according to a study published online Feb. 25 in Therapeutic Advances in Musculoskeletal Disease.Jasvinder A. Singh, M.B.B.S., M.P.H., and John Cleveland, M.D., both from the University of Alabama at Birmingham, used data from the U.S. National Inpatient Sample (1998 to 2014) to examine the frequency of seven common cardiac and orthopedic procedures in hospitalized people with gout and RA compared to the general population.

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Gout ‘more than doubles’ risk of kidney failure

Largest ever study on subject uses data from more than 620,000 patients in UK health system


Date: August 28, 2019
Source:University of Limerick
Summary: Patients with gout are at increased risk of chronic kidney disease and kidney failure, according to new research.

Patients with gout are at increased risk of chronic kidney disease and kidney failure, according to new University of Limerick (UL), Ireland led research.

In one of the largest and most detailed studies ever conducted, patients recruited in general practice with a diagnosis of gout were more than twice as likely to develop kidney failure than those without, according to the study led by researchers at University of Limerick’s (UL) Graduate Entry Medical School (GEMS).

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