Volume 53, Issue 2 , Pages 273-280, February 2009
Association of the Q121 Variant of ENPP1 Gene With Decreased Kidney Function Among Patients With Type 2 Diabetes
Background
Insulin resistance has a role in diabetic kidney complications. The K121Q (lysine to glutamine substitution at amino acid 121, encoded by single-nucleotide polymorphism rs1044498) variant of the ectonucleotide pyrophosphatase/phosphodiesterase gene (ENPP1) has been associated with insulin resistance and related vascular complications in patients with type 2 diabetes (T2D) in many, although not all, studies. This study investigated whether the ENPP1 Q121 variant modulates the risk of decreased glomerular filtration rate (GFR) in patients with T2D.
Study Design
Cross-sectional study.
Setting & Participants
2 diabetes units from Italy (in Gargano and Padua) and 1 from the United States (Boston, MA) recruited a total of 1,392 patients with T2D.
Predictor
The ENPP1 Q121 variant.
Measurements
Estimated GFR from serum creatinine, urinary albumin excretion, blood pressure, hemoglobin A1c, triglycerides, total cholesterol, and high-density lipoprotein cholesterol.
Outcomes
Decreased GFRs (ie, estimated GFR <60 mL/min/1.73 m2).
Results
In the Gargano and Boston populations, according to the dominant model of inheritance, Q121 carriers (ie, individual with either KQ or QQ alleles) had an increased risk of decreased GFR: odds ratios (ORs) of 1.69 (95% confidence interval [CI], 1.1 to 2.6) and 1.50 (95% CI, 1.0 to 2.2), respectively. In the Padua set, the association was in the same direction, but did not reach formal statistical significance (OR, 1.77; 95% CI, 0.7 to 4.5). When the 3 studies were pooled, Q121 carriers showed an increased risk of decreased GFR (OR, 1.58; 95% CI, 1.2 to 2.1; P = 0.002). Also, pooled mean differences in absolute GFRs were different across genotype groups, with Q121 carriers showing lower GFRs compared with KK individuals (P = 0.04).
Limitations
P values not approaching a genome-wide level of significance.
Conclusions
Our data suggest that patients with T2D carrying the ENPP1 Q121 variant are at increased risk of decreased GFR.
Index Words: Gene polymorphism, insulin resistance, vascular diabetic complications, PC-1
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Originally published online as doi:10.1053/j.ajkd.2008.07.040 on October 28, 2008.
PII: S0272-6386(08)01298-5
doi:10.1053/j.ajkd.2008.07.040
© 2009 National Kidney Foundation, Inc. Published by Elsevier Inc All rights reserved.
Refers to erratum:
- Errata
Volume 53, Issue 2 , Pages 273-280, February 2009
