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

A. Mantovani, C. Zusi, E. Sani, A. Colecchia, G. Lippi, G. L. Zaza, L. Valenti, C. D. Byrne, C. Maffeis, E. Bonora, G. Targher

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Abstract

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 (eGFR CKD-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 (eGFR CKD-EPI < 60 mL/min/1.73 m 2 or abnormal albuminuria). Compared to those with G/C or C/C genotypes, patients with G/G genotype had significantly lower eGFR CKD-EPI (63.7 ± 11 vs. 77.4 ± 17 vs. 81.9 ± 15 mL/min/1.73 m 2 , 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 A 1c , HOMA-estimated insulin resistance, systolic blood pressure, hypertension treatment and FLI ≥ 60, rs738409 G/G genotype was independently associated with both lower eGFR CKD-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 eGFR CKD-EPI and higher prevalence of CKD.

Original languageEnglish
Pages (from-to)480-487
JournalDiabetes and Metabolism
Volume45
Issue number5
DOIs
Publication statusPublished - Jan 1 2019

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Chronic Renal Insufficiency
Kidney
Genotype
Albuminuria
Non-alcoholic Fatty Liver Disease
Blood Pressure
Hemoglobin A
Fatty Liver
Ambulatory Care
Glomerular Filtration Rate
Insulin Resistance
Ultrasonography
Epidemiology
Odds Ratio
Urine
Hypertension
Polymerase Chain Reaction

Keywords

  • Adiponutrin
  • Chronic kidney disease
  • CKD
  • NAFLD
  • Type 2 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Association between PNPLA3rs738409 polymorphism decreased kidney function in postmenopausal type 2 diabetic women with or without non-alcoholic fatty liver disease. / Mantovani, A.; Zusi, C.; Sani, E.; Colecchia, A.; Lippi, G.; Zaza, G. L.; Valenti, L.; Byrne, C. D.; Maffeis, C.; Bonora, E.; Targher, G.

In: Diabetes and Metabolism, Vol. 45, No. 5, 01.01.2019, p. 480-487.

Research output: Contribution to journalArticle

Mantovani, A. ; Zusi, C. ; Sani, E. ; Colecchia, A. ; Lippi, G. ; Zaza, G. L. ; Valenti, L. ; Byrne, C. D. ; Maffeis, C. ; Bonora, E. ; Targher, G. / Association between PNPLA3rs738409 polymorphism decreased kidney function in postmenopausal type 2 diabetic women with or without non-alcoholic fatty liver disease. In: Diabetes and Metabolism. 2019 ; Vol. 45, No. 5. pp. 480-487.
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title = "Association between PNPLA3rs738409 polymorphism decreased kidney function in postmenopausal type 2 diabetic women with or without non-alcoholic fatty liver disease",
abstract = "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 (eGFR CKD-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 (eGFR CKD-EPI < 60 mL/min/1.73 m 2 or abnormal albuminuria). Compared to those with G/C or C/C genotypes, patients with G/G genotype had significantly lower eGFR CKD-EPI (63.7 ± 11 vs. 77.4 ± 17 vs. 81.9 ± 15 mL/min/1.73 m 2 , 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 A 1c , HOMA-estimated insulin resistance, systolic blood pressure, hypertension treatment and FLI ≥ 60, rs738409 G/G genotype was independently associated with both lower eGFR CKD-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 eGFR CKD-EPI and higher prevalence of CKD.",
keywords = "Adiponutrin, Chronic kidney disease, CKD, NAFLD, Type 2 diabetes",
author = "A. Mantovani and C. Zusi and E. Sani and A. Colecchia and G. Lippi and Zaza, {G. L.} and L. Valenti and Byrne, {C. D.} and C. Maffeis and E. Bonora and G. Targher",
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TY - JOUR

T1 - Association between PNPLA3rs738409 polymorphism decreased kidney function in postmenopausal type 2 diabetic women with or without non-alcoholic fatty liver disease

AU - Mantovani, A.

AU - Zusi, C.

AU - Sani, E.

AU - Colecchia, A.

AU - Lippi, G.

AU - Zaza, G. L.

AU - Valenti, L.

AU - Byrne, C. D.

AU - Maffeis, C.

AU - Bonora, E.

AU - Targher, G.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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 (eGFR CKD-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 (eGFR CKD-EPI < 60 mL/min/1.73 m 2 or abnormal albuminuria). Compared to those with G/C or C/C genotypes, patients with G/G genotype had significantly lower eGFR CKD-EPI (63.7 ± 11 vs. 77.4 ± 17 vs. 81.9 ± 15 mL/min/1.73 m 2 , 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 A 1c , HOMA-estimated insulin resistance, systolic blood pressure, hypertension treatment and FLI ≥ 60, rs738409 G/G genotype was independently associated with both lower eGFR CKD-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 eGFR CKD-EPI and higher prevalence of CKD.

AB - 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 (eGFR CKD-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 (eGFR CKD-EPI < 60 mL/min/1.73 m 2 or abnormal albuminuria). Compared to those with G/C or C/C genotypes, patients with G/G genotype had significantly lower eGFR CKD-EPI (63.7 ± 11 vs. 77.4 ± 17 vs. 81.9 ± 15 mL/min/1.73 m 2 , 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 A 1c , HOMA-estimated insulin resistance, systolic blood pressure, hypertension treatment and FLI ≥ 60, rs738409 G/G genotype was independently associated with both lower eGFR CKD-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 eGFR CKD-EPI and higher prevalence of CKD.

KW - Adiponutrin

KW - Chronic kidney disease

KW - CKD

KW - NAFLD

KW - Type 2 diabetes

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U2 - 10.1016/j.diabet.2019.01.011

DO - 10.1016/j.diabet.2019.01.011

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