**Question:** Asians & Native Americans may flush & feel ill after drinking small amount of ethanol. This reaction is due to genetic variation in which enzyme:

A. alcohol dehydrogenase (ADH)
B. aldehyde dehydrogenase (ALDH)
C. cytochrome P450 2E1
D. solute carrier organic anion transporter 1 (SLC22A2)

**Core Concept:** Ethanol is a common alcohol found in beverages like wine, beer, and spirits. When consumed, ethanol is primarily broken down by enzymes in the liver into acetaldehyde, which is then further broken down into acetic acid. This process is carried out by different enzymes, each with a specific role.

**Why the Correct Answer is Right:** The correct answer, **cytochrome P450 2E1 (CYP2E1)**, is involved in the initial stage of ethanol biotransformation. CYP2E1 is an enzyme that converts ethanol into acetaldehyde. The genetic variation in this enzyme can lead to a reduced activity, resulting in a slower rate of ethanol breakdown. This, in turn, results in higher levels of acetaldehyde in the bloodstream, causing flushing, nausea, and other adverse reactions in susceptible individuals.

**Why Each Wrong Option is Incorrect:**

A. **Alcohol dehydrogenase (ADH)** and **aldose dehydrogenase (ALDH)** are enzymes involved in ethanol and acetaldehyde breakdown, respectively. These enzymes are not the cause of the adverse reactions seen in Asians and Native Americans.

B. **Aldehyde dehydrogenase (ALDH)** is responsible for breaking down acetaldehyde into acetic acid, not ethanol. This enzyme does not play a role in the adverse reactions described.

C. **Solute carrier organic anion transporter 1 (SLC22A2)** is a transporter protein involved in the uptake of various organic anions, including some drugs. It is not directly responsible for the adverse reactions due to ethanol consumption.

**Clinical Pearl:** The adverse reactions in Asians and Native Americans are primarily due to genetic variations in CYP2E1, which affects ethanol biotransformation and raises acetaldehyde levels. This can lead to flushing, nausea, and other negative effects when consuming alcohol. Understanding these genetic variations can help healthcare professionals predict and manage patients' reactions to ethanol-containing substances.