Flavin-Containing Monooxygenase 3 Polymorphisms in 13 Ethnic Populations from Europe, East Asia and Sub-Saharan Africa: Frequency and Linkage Analysis

Abstract

Aims: To investigate intra- and inter-ethnic differences in three widespread (E158K, V257M and E308G) and two African-specific (D132H and L360P) flavin-containing monooxygenase 3 (FMO3) polymorphisms. Materials & methods: Allele frequencies were determined by TaqMan^® allelic discrimination assay in 2152 healthy volunteers from Europe (Swedes, Italians and Turks), East Asia (Japanese) and sub-Saharan Africa (nine ethnic groups covering eastern, southern and western regions), followed by haplotype and linkage analysis. Results: Significant subpopulation differences (p < 0.001) in allele frequencies were found for E158K, V257M and E308G in Europeans and regional differences (p < 0.01) for D132H among Africans. No carrier of P360 was identified. Cis-linkage between G308 and K158 was confirmed with the compound variant (K158/G308) being found in a high proportion (12.0–38.3%) of non-African subjects, but rarely (1.3%) among Africans. Conclusions: Distribution of functionally relevant FMO3 polymorphisms varies not only between ethnicities but also within. The K158/G308 variant may have potential clinical importance primarily in non-African populations due to its low prevalence in Africa.

KEYWORDS::

• FMO3
• genetic linkage
• pharmacogenetics
• polymorphism
• population diversity
• sub-Saharan Africans

Financial & competing interests disclosure

This study was supported by grants from the Swedish Research Council, the European & Developing Countries Clinical Trials Partnership (EDCTP) and the Gazi University Research Fund. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This study was supported by grants from the Swedish Research Council, the European & Developing Countries Clinical Trials Partnership (EDCTP) and the Gazi University Research Fund. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.