Effect modification by region in the associations ofLEP G2548AandLEPR Q223Rpolymorphisms with statin-induced CK elevation

Abstract

We investigated the associations of LEP G2548A and LEPR Q223R polymorphisms with statin-induced creatine kinase (CK) elevation among Chinese patients with hyperlipidemia. A total of587 enrolled individuals were treated with 20 mg/d oral simvastatin for 8 consecutive weeks. Genotyping of LEP G2548A and LEPR Q223R were conducted using PCR-RFLP. Multiple regression analyses showed that, in the Dongzhi region only, patients carrying the LEP AA genotype had a significantly greater increase in CK levels compared to those carrying the AG+GG genotypes after four weeks (P = 0.004) and eight weeks (P < 0.001) consecutive simvastatin treatment. Patients were further divided into three groups based on the tertiles of the CK distribution. Compared to subjects in the lowest tertile of CK elevation, the adjusted relative odds of having the AG+GG genotypes among subjects in the highest tertile was 0.5 (95% CI, 0.3 to 0.7) and 0.4 (95% CI, 0.2 to 0.6) after the fourth and eighth weeks, respectively. The interaction terms between the Beijing or Dongzhi region and the LEP GA+AA genotypes were marginally significant for CK elevation at the fourth week (P = 0.057) and significant for CK elevation at the eighth week (P = 0.002). The adverse effect of the LEP G2548A polymorphism on increasing CK levels may be dependent on the environmental milieu. It suggests that lifestyle interventions might offset the side effects of simvastatin therapy among those with genetic susceptibility. Further research is needed to identify specific individual-level factors for clinical practice that modify the effect of genotype.

Pharmacogenomics of response to statin treatment and susceptibility to statin-induced adverse drug reactions in Asians: a scoping review

“…Five papers investigated associations between various genetic variants with statin-induced ADRs, studying the effects of either just one statin [ 33 , 77 ] or multiple statins [ 78 , 79 , 80 ] ( Table 2 ). As the studies used different methods in determining statin-induced ADRs and studied different genes, direct comparisons to derive a definitive conclusion were not possible.…”

“…The study with the largest cohort classified statin-induced myopathy based on CK levels and geographic location in China (392 patients from Dongzhi and 195 patients from Beijing) over two time points, specifically after 4 weeks’ and 8 weeks’ treatment with simvastatin [ 77 ]. Jiang et al [ 77 ] only found significant elevation of CK levels among patients in Dongzhi with either the AA genotype in the LEP G2548A variant and RR or QQ genotypes of the LEPR Q233R variant. However, this finding was not replicated in patients from Beijing.…”

Polimorfismos g-2548a en el gen de leptina y q223r en el gen del receptor de leptina: una revisión de su relación con el sobrepeso y la obesidad

“…Como ya se ha mencionado, la relevancia del trasfondo genético en el desarrollo de la obesidad y sus comorbilidades es demostrada, pero las asociaciones aun no son definitivas (Garcés et al, 2016). La frecuencia del alelo G en los SNP de LEP, se ha encontrado "significativamente mayor" en personas con sobrepeso y obesidad, cuando se ha asociado con niveles de leptina, IMC, masa grasa y presión arterial (Jiang et al, 2017). Cabe mencionar que otros estudios no han logrado demostrar alguna asociación consistente entre los polimorfismos de LEP o LEPR y obesidad (Garavito et al, 2020).…”

“…Los polimorfismos LEP G-2548A y LEPR Q223R han sido variables asociadas a diferentes comorbilidades en diferentes poblaciones (Jiang et al, 2017). Meshkani y colaboradores (2016) investigaron la asociación de estas variantes génicas con diabetes tipo 2, en población iraní de ambos sexos.…”