NPHS2 R229Q functional variant is associated with microalbuminuria in the general population.

Background: Microalbuminuria is a risk factor for developing end-stage renal disease and cardiovascular events. Mutations in NPHS2 have been shown to cause autosomal-recessive nephrotic syndrome. Recently, a functional polymorphism of this gene (R229Q) was described and associated with a maturity-onset form of nephrotic syndrome. We have investigated whether the carrier status of this novel genetic variant is associated with microalbuminuria in individuals from the general population.

Methods: Demographic, cardiovascular risk factors, and renal phenotypes in 1577 individuals from a cross-sectional-based study were collected following the general guidelines of the WHO-MONICA project (monitoring trends and determinants in cardiovascular diseases). Blood and urine samples were obtained. Microalbuminuria was determined using a semiquantitative protocol, and DNA was extracted from peripheral lymphocytes.

Results: A strong association was found between the 229Q allele and microalbuminuria (P= 0.008). The presence of the 229Q allele was still associated with a 2.77-fold increased risk of presenting microalbuminuria even after adjustment for age, ethnicity, hypertension, obesity, and diabetes in a multiple logistic regression model. In addition, a statistically significant interaction was identified between the presence of the 229Q allele and body mass index (BMI) (P= 0.01), suggesting an additive effect between the 229Q allele and other risk factors for microalbuminuria.

Conclusion: These data have important implications for the understanding of microalbuminuria in the general population and may contribute to better ways of disease prediction and prevention.