BPA: Genetics and Detoxification

BPA, a chemical found in some plastics, has been linked to a variety of effects on people including obesity, insulin resistance, and epigenetic effects on the fetus.  It is everywhere in our food supply; 92% of people had BPA in their urine. [ref]

My question today…  does BPA affect everyone the same way or do genetic variants play a role?

Recent studies on BPA show:

First, let’s take a look at recent studies on BPA to see if it is really a problem.

  • Obesity:  A 2016 study found that BPA exposure caused “adipocyte metabolic dysfunction and inflammation, thereby increasing the risk of developing obesity-related diseases.” [ref]
  • Decreased testosterone: A study released in July 2016 showed that male adolescent testosterone levels were decreased for those with higher levels of BPA.  [ref]
  • ADHD:  A June 2016 study showed a 5x risk of ADHD for those with higher urinary BPA concentrations. [ref]
  • Insulin resistance: BPA levels are tied to obesity and insulin resistance in adult males. [ref] A Nov. 2016 study also showed that higher urinary BPA levels correlated with higher BMI and insulin levels in women. [ref]
  • Obesity: Epigenetic effects on the expression of genes involved in lipid accumulation [ref]
  • Lungs: BPA disrupts fetal lung maturation through the following pathway: “BPA signals through ERβ to activate the NF-κB signaling pathway. Taken together, these findings demonstrate that BPA acts on ERβ to activate the NF-κB signaling pathway, which in turn leads to diminished GR activity and consequent repression of ENaCγ expression in lung epithelial cells.”[ref]
  • Insulin resistance: Higher levels of BPA associated with higher insulin resistance in children regardless of BMI. [ref]
  • Fat: Prenatal BPA levels were associated with fat mass index at age 7 [ref]
  • Cancer: Liver cancer at a young age (mice) with both 50 ug/kg/day and 50mg/kg BPA dosage in mice. [ref] Note that the 50 ug/kg/day is considered low dose and within EPA thresholds.
  • Genital malformations: A small study in children with male genital malformations found that BPA exposure inhibited metalloproteinase-11 expression more so in MGF children than in the control group.  [ref]
  • Obesity: “Both perinatal exposure alone and perinatal plus peripubertal exposure to environmentally relevant levels of BPA resulted in lasting effects on body weight and body composition.” [ref]
  • Phase I Detoxification: BPA causes an upregulation of CYP2C9 expression [ref]

Genetic variant responses to BPA

Oxidative Stress:

BPA exposure increases oxidative stress and mitochondrial dysfunction.  A study looked at BPA exposure in children with autism found that all children (with and without autism) had an increase in oxidative stress and mitochondrial dysfunction when exposed to BPA.[ref] Another study found increased oxidative stress biomarkers in pregnant women based on BPA exposure. [ref]

COX2 gene

  • rs5277 – Those with GG have a 3x increase in risk for liver dysfunction with BPA exposure (study on elderly population) [ref]

CAT gene

  • rs769217 – CT has a 4x increased risk of liver dysfunction in the elderly with BPA exposure [ref]

SOD2 gene

  • rs4880– AA has OR=2.59 for liver dysfunction in the elderly with BPA exposure [ref]

Metabolism of BPA:

UGT2B15  metabolizes BPA (through glucuronidation)[ref]; “the polymorphic alleles of UGT2B15 are closely associated with variations in the metabolism and toxicity of BPA.”[ref]

A study looked at the expression of UGT2B15 during the third trimester and in infants (3 – 15 weeks).  UGT2B15 levels varied (by 31 fold) among the group due in part to gender and UGT2B15 polymorphisms. [ref]

rs1902023 (A is the minor allele, also referred to as  253G>T and UGT2B15*2)

  • A allele causes decreased enzyme activity [ref]

rs3100 (G is the minor allele, also referred to as 761T>C)

  • G allele causes decreased enzyme activity [ref]

UGT1A1 – also metabolizes BPA through glucuronidation [ref]

rs34983651 — dbSNP has the insertion (I or AT)  as UGT1A1*28 [ref] but snpedia.com has the deletion (D) as UGT1A1*28

  • lower liver clearance of BPA with UGT1A1*28 (homozygous had much lower liver clearance) [ref]
  • 10x lower glucuronidation in breast tissue for UGT1A1*28 [ref]

SULT1A1

The BPA that isn’t metabolized through glucuronidation usually gets taken care of through SULT1A1.  Mouse studies show that obese livers are less able to sulfate BPA than lean mice.  “Taken together these findings establish a profoundly reduced capacity of BPA elimination via sulfonation in obese or diabetic individuals and in those with fatty or cirrhotic livers versus individuals with healthy livers.” [ref]

rs9282861 or i6018900 (T is the minor allele, also known as SULT1A1*2)

  • low activity of the enzyme [ref] [ref]

Caffeine induces the SULT1A1 enzyme (rat study) [ref][ref]

Detoxification of BPA:

A recent study on the detoxification of BPA in the liver found that the process depends on the stored retinol (vitamin A) in the liver.  If you are a vegetarian and depending on beta carotene as your source of vitamin A, you may want to check and see if you convert beta carotene to retinol well.

More to read:

 

Updated 2/6/17

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