Association between PNPLA3rs738409 polymorphism decreased kidney function in postmenopausal type 2 diabetic women with or without non-alcoholic fatty liver disease

AIM: Evidence is emerging that PNPLA3 rs738409 polymorphism (the major genetic variant associated with susceptibility to non-alcoholic fatty liver disease [NAFLD]) is associated with chronic kidney disease (CKD) in non-diabetic individuals. Currently, little is known about this association in type 2 diabetic (T2DM) patients with and without NAFLD. METHODS: We studied 101 Caucasian post-menopausal women with T2DM, consecutively attending our diabetes outpatient service during a 3-month period. Glomerular filtration rate (eGFRCKD-EPI) was estimated using the CKD-Epidemiology Collaboration (CKD-EPI) equation, whilst albuminuria was measured with an immunonephelometric assay on morning spot urine samples. NAFLD was detected either by fatty liver index (FLI ≥ 60, n = 101) or by ultrasonography (n = 77). Genotyping was performed by TaqMan-Based RT-PCR system. RESULTS: Eight patients had G/G, 41 G/C and 52 C/C PNPLA3 rs738409 genotypes, and 21 (20.8%) patients had CKD (eGFRCKD-EPI < 60 mL/min/1.73 m2 or abnormal albuminuria). Compared to those with G/C or C/C genotypes, patients with G/G genotype had significantly lower eGFRCKD-EPI (63.7 ± 11 vs. 77.4 ± 17 vs. 81.9 ± 15 mL/min/1.73 m2, P = 0.014) and higher prevalence of CKD (50% vs. 24.4% vs. 13.5%, P = 0.04). After adjustment for age, duration of diabetes, haemoglobin A1c, HOMA-estimated insulin resistance, systolic blood pressure, hypertension treatment and FLI ≥ 60, rs738409 G/G genotype was independently associated with both lower eGFRCKD-EPI (β coefficient: -15.5, 95% CI -26.0 to -5.0, P = 0.004) and higher risk of CKD (adjusted-odds ratio 8.05, 95% CI 1.26-41.4, P = 0.03). Similar results were found when we adjusted for hepatic steatosis on ultrasography (instead of FLI ≥ 60). CONCLUSION: Regardless of the presence of NAFLD and common cardio-renal risk factors, in post-menopausal women with T2DM, the G/G genotype of rs738409 in the PNPLA3 gene was strongly associated with lower eGFRCKD-EPI and higher prevalence of CKD