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Background <p>Statin usage has increased significantly in India due to the very high incidence of dyslipidemia, however, approximately 18% of the population is at risk for statin-induced myopathy. Hence, we conducted a population-level screening for pharmacogenetic determinants of statin therapy, particularly Solute Carrier Organic Anion Transporter Family Member 1B1 (SLCO1B1) and ATP-binding cassette sub-family G member 2 (ABCG2).</p> Materials and methods <p>Whole exome sequencing was performed in 2180 subjects, and the variant data were segregated further into diplotypes and phenotypes.</p> Results <p>SLCO1B1 normal function was observed in 81% of subjects (diplotypes: 1/*1, *1/*14, *1/*20, *1/*37, and *37/*37). Increased SLCO1B1 function was observed in 8% of the population (diplotypes: *14/*14 and *20/*20). Decreased function of SLCO1B1 (*1/*15) was observed in 5% of the population. Poor function of SLCO1B1 was observed in 6% of the population (diplotypes: *5/*5 and *15/*15). About 81.46% of subjects displayed normal ABCG2 function, while 17.34% had decreased and 1.19% had poor function. Combined SLCO1B1/ABCG2 functional defects were observed in 7.4% of subjects. Two rare SLCO1B1 variants in SLCO1B1 i.e., rs201722521 and rs71581988, were reported to affect the binding affinity of certain statins. The SLCO1B1 C-C-C-A-A-A haplotype was associated with a 2.22-fold risk for hyperbilirubinemia (95% CI: 1.13–4.36, <i>p</i> = 0.02). Rosuvastatin’s daily dose of up to 10&#xa0;mg is well tolerated across the different SLCO1B1 functionality groups.</p> Conclusions <p>This study demonstrates that 11% of our population exhibit decreased or poor function of SLCO1B1 and 7.4% exhibit decreased or poor function of both SLCO1B1 and ABCG2, necessitating adjustments in daily statin doses to minimize the risk for statin-induced myopathy.</p> Graphical Abstract <p></p>

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Unveiling hidden risks: pharmacogenetic insights from a cross-sectional study of statin therapy in the Indian population

  • 期刊论文

  • 发表日期：

    2025年6月9日

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  • Shaik Mohammad Naushad,
  • Palani Kumar Palanichamy,
  • Jagadeesh Babu Sreemanthula,
  • Yadam Reddy Kanaka Durga Devi,
  • Palakonda Gopi,
  • Tajamul Hussain,
  • Vijay Kumar Kutala

摘要

Background

Statin usage has increased significantly in India due to the very high incidence of dyslipidemia, however, approximately 18% of the population is at risk for statin-induced myopathy. Hence, we conducted a population-level screening for pharmacogenetic determinants of statin therapy, particularly Solute Carrier Organic Anion Transporter Family Member 1B1 (SLCO1B1) and ATP-binding cassette sub-family G member 2 (ABCG2).

Materials and methods

Whole exome sequencing was performed in 2180 subjects, and the variant data were segregated further into diplotypes and phenotypes.

Results

SLCO1B1 normal function was observed in 81% of subjects (diplotypes: 1/*1, *1/*14, *1/*20, *1/*37, and *37/*37). Increased SLCO1B1 function was observed in 8% of the population (diplotypes: *14/*14 and *20/*20). Decreased function of SLCO1B1 (*1/*15) was observed in 5% of the population. Poor function of SLCO1B1 was observed in 6% of the population (diplotypes: *5/*5 and *15/*15). About 81.46% of subjects displayed normal ABCG2 function, while 17.34% had decreased and 1.19% had poor function. Combined SLCO1B1/ABCG2 functional defects were observed in 7.4% of subjects. Two rare SLCO1B1 variants in SLCO1B1 i.e., rs201722521 and rs71581988, were reported to affect the binding affinity of certain statins. The SLCO1B1 C-C-C-A-A-A haplotype was associated with a 2.22-fold risk for hyperbilirubinemia (95% CI: 1.13–4.36, p = 0.02). Rosuvastatin’s daily dose of up to 10 mg is well tolerated across the different SLCO1B1 functionality groups.

Conclusions

This study demonstrates that 11% of our population exhibit decreased or poor function of SLCO1B1 and 7.4% exhibit decreased or poor function of both SLCO1B1 and ABCG2, necessitating adjustments in daily statin doses to minimize the risk for statin-induced myopathy.

Graphical Abstract