Cryptogenic Stroke in the Young: Role of Candidate Gene Polymorphisms in Indian Patients with Ischemic Etiology

Context: Strokes that remain without a definite cause even after an extensive workup, termed cryptogenic strokes, constitute up to 30-40% of ischemic strokes (ISs) in the young. Some of them can have a genetic basis. However, the well-established genetic causes account for only a small percentage of these cases. Aim: To evaluate the association of cryptogenic young IS with 16 candidate gene polymorphisms. Settings and Design: A case-control study with cryptogenic young IS patients (South and North Indians; n = 105) and age, sex, and ethnicity-matched controls (n = 215). Subjects and Methods: Genotyping was carried out by PCR-RFLP method using DNA extracted from the blood. Statistical Analysis Used: Association of the genotypes with the disease was studied using Chi-square test. Results: MTHFR rs1801133 and KNG1 rs710446 showed significant statistical association with cryptogenic young IS (P = 0.0261 and 0.0157, respectively) in the Indian population. Significant association of KNG1 rs710446 (P 0.0036) and FXII rs1801020 (P 0.0376) with cryptogenic young stroke in South Indian males, SERPINC1 rs2227589 in South Indian female patients (P = 0.0374), and CYP4V2 rs13146272 in North Indian males (P = 0.0293) was observed. Conclusions: Our study indicates that in the Indian population MTHFR rs1801133, KNG rs710446, FXII rs1801020, SERPINC1 rs2227589, CYP4V2 rs13146272, and FXIII V34L may be significant risk factors for cryptogenic IS in the young. In addition, ethnicity and gender play a significant role. Further studies with larger sample size are required to completely establish these polymorphisms as risk factors for cryptogenic IS in young Indians.