What is the prevalence of slow acetylators, specifically individuals with impaired N-acetyltransferase (NAT) enzyme activity, in the Indian population?

From the Guidelines

The prevalence of slow acetylators in the Indian population is not explicitly stated in the provided evidence, but it can be inferred that the frequency of slow metabolism is lower in Indian populations compared to non-Indian Asian populations. This is based on the study by 1, which mentions that single-nucleotide polymorphisms contributing to slow metabolism are represented in higher frequencies among non-Indian Asian populations than among other populations. Some key points to consider in this context include:

• The study focuses on the pharmacokinetics of voriconazole and its interaction with CYP2C19, CYP2C9, and CYP3A4 enzymes, rather than N-acetyltransferase (NAT) enzyme activity directly.
• Allelic polymorphisms in CYP2C19 may result in rapid or slow metabolism of voriconazole, but this does not directly inform us about the prevalence of slow acetylators in the Indian population.
• The provided evidence does not offer a clear estimate of the prevalence of slow acetylators in the Indian population, and therefore, clinicians should exercise caution when prescribing medications that are metabolized by NAT enzymes, such as isoniazid, hydralazine, procainamide, and sulfonamide antibiotics, and consider the potential for variable drug clearance in this population. Key considerations for clinicians include:
• Being aware of the potential for pharmacogenetic variation in the Indian population and its impact on drug metabolism.
• Carefully reviewing patient medications and medical history to minimize the risk of adverse effects.
• Considering alternative dosing strategies or monitoring plans for patients who may be slow acetylators.
• Staying up-to-date with the latest research and guidelines on pharmacogenetics and personalized medicine to optimize patient care.

From the FDA Drug Label

The rate of acetylation is genetically determined Approximately 50 percent of Blacks and Caucasians are "slow inacti- vators", and the rest are "rapid inactivators"; the majority of Eskimos and Orientals are" rapid inactivators. "

The FDA drug label does not answer the question about the prevalence of slow acetylators in the Indian population.

From the Research

Prevalence of Slow Acetylators in the Indian Population

• The prevalence of slow acetylators in the Indian population has been studied in several research papers 2, 3, 4, 5, 6.
• A study published in 2013 found that the overall frequency of slow acetylator haplotypes in the Indian population was 65% 2.
• Another study published in 1976 reported that the proportion of slow acetylators among South Indians was about 60% 3.
• A study published in 2003 found that slow acetylators were predominant in the ethnic populations of South India, with a frequency of 74% 4.
• A study published in 2009 reported that the distribution of slow, intermediate, and fast acetylators in a southwestern Indian population was 55%, 32%, and 13%, respectively 5.
• A more recent study published in 2024 found that the genotype frequency of slow acetylators in the Indian population was 53.46% 6.

NAT2 Gene Polymorphisms and Acetylator Status

• The NAT2 gene polymorphisms have been found to vary remarkably between populations of different ethnic origin 5.
• The NAT2 gene determines the individual's acetylator status to metabolize drugs and xenobiotics, influencing their toxicity and efficacy profiles 5.
• The association between NAT2 genotypes and plasma isoniazid concentrations has been investigated in several studies 2, 5, 6.
• Patients with slow acetylator status have been found to have significantly increased serum isoniazid concentrations and a higher risk of developing drug-induced hepatotoxicity 6.

Regional Variations in Acetylator Status

• There are regional variations in the acetylator status of the Indian population, with different frequencies of slow, intermediate, and fast acetylators reported in different studies 2, 3, 4, 5, 6.
• The frequency of slow acetylators has been found to be higher in South India compared to other regions 3, 4.
• Further studies are needed to understand the relationship between NAT2 genotypes and adverse drug events in different regions of India 5.