Elevated prevalence of hereditary thrombophilia variants in an endogamous jewish-Mexican cohort Free

Background: Hereditary thrombophilias (HTs) are genetic disorders associated with an increased risk of venous thromboembolism (VTE) and pregnancy-related complications. The common inherited thrombophilias include deficiencies of protein C, protein S, and antithrombin, as well as pathogenic variants in the F5 and F2 genes. According to the American Society of Hematology, the Factor V Leiden variant occurs in approximately 3–7% of the general population, while the F2 p.G20210A variant is found in 0.7–4%. Certain populations exhibit higher frequencies; in Israel, Factor V Leiden prevalence reaches up to 14% among Turkish and Greek Jews, and prothrombin variants are notably high in Georgian Jews (14%) and Turkish/Greek Jews (8%). These population-specific prevalence patterns are often influenced by genetic drift and founder effects, particularly in endogamous communities.

Objective: To determine the prevalence and spectrum of HT-related genetic variants in a genetically isolated, endogamous Jewish-Mexican population.

Methods: We conducted a retrospective analysis of 582 unrelated individuals (aged 18–44 years) who underwent clinical exome sequencing and consented to thrombophilia-related genetic testing. A targeted gene panel was used to assess variants in F2, F5, PROC, PROS1, SERPINC1, and MTHFR. Pathogenic and likely pathogenic variants were reported..

Results: Out of 582 individuals, 118 (20.3%) were found to carry pathogenic or likely pathogenic variants associated with HTs. The most prevalent variant was F5 Leiden (F5:c.1601G>A), detected in 84 heterozygous individuals (14.4%), 4 homozygous individuals (0.7%), and 1 compound heterozygote. The F2 variant, known as G20210A (F2:c.*97G>A) was identified in 30 heterozygotes (5.1%), and one individual carried a rare F2 c.1499G>A variant (0.17%). Variants in PROC and PROS1 were each found in one individual (0.17%). No pathogenic variants were observed in SERPINC1 in this cohort.

Conclusion: This study is the first to characterize the genetic prevalence of hereditary thrombophilia variants in a Jewish-Mexican population. The notably high frequency of F5 Leiden and F2 G20210A aligns with observations in other genetically isolated Jewish populations, underscoring the impact of endogamy on variant enrichment and the importance of understanding genetic background in population-based studies of thrombophilia.