Elsevier

Gene

Volume 520, Issue 1, 10 May 2013, Pages 73-76
Gene

Short communication
Association between a MYH9 polymorphism (rs3752462) and renal function in the Spanish RENASTUR cohort

https://doi.org/10.1016/j.gene.2013.02.024Get rights and content

Highlights

  • We genotyped two MYH9 polymorphisms in an elderly population.

  • SNP rs3752462 was significantly related with glomerular filtration rate.

  • This association was independent of other risk factors for impaired renal function.

Abstract

The MYH9 gene encodes a protein that is expressed in the kidney glomerular podocytes. MYH9 single nucleotide polymorphisms (SNPs) have been linked to the risk for chronic kidney disease (CKD) and end stage renal disease. Our aim was to determine whether MYH9 SNPs were associated with renal disease in Spanish Caucasians. The RENASTUR cohort consisted of 592 Spanish Caucasians, aged 55–85 years. They were genotyped for SNPs rs3752462 and rs4821480, which tagged haplotype E. The main values between individuals with a glomerular filtration rate (eGFR) < 60 and ≥ 60 ml/min/1.73 m2 were statistically compared. The next variables were significantly associated with the eGFR in the univariate analysis: age, gender, type 2 diabetes, total cholesterol, total LDL-cholesterol, and the MYH9 rs3752462 (TC + TT genotypes; p = 0.003). This SNP remained significantly associated with the eGFR in the multivariate analysis.

In conclusion, SNP rs3752462 was an independent predictor of reduced eGFR in the Spanish RENASTUR population. The genotyping of this MYH9 SNP could help to identify individuals at risk of developing CKD.

Introduction

The estimated glomerular filtration rate (eGFR) is commonly used to define renal function and identify individuals with chronic kidney disease (CKD). The Kidney Disease Outcome Quality Initiative (K/DOQI) defined CKD as the presence of renal impairment with an eGFR < 60 (National Kidney Foundation, 2002). Based on this definition the EPIRCE study (Epidemiology of Chronic Kidney Disease in Spain) estimated that approximately 10% of the Spanish adult population had some degree of CKD, and similar values were also estimated from other epidemiological studies (Coresh et al., 2007, Otero et al., 2010). CKD is a strong predictor of end stage renal disease (ESRD), cardiovascular morbidity, and mortality. In addition to well known risk factors such as hypertension and diabetes, recent genome wide association studies (GWAs) linked several single nucleotide polymorphisms (SNPs) to eGFR and prevalent CKD (Köttgen et al., 2009, Köttgen et al., 2010). Some of these SNPs were also associated with the progression to ESRD (Böger et al., 2011).

The MYH9 gene encodes a myosin heavy chain protein expressed in glomerular podocytes and mesangial cells (Marini et al., 2006). Recent studies linked MYH9 SNPs/haplotypes to the risk of developing focal segmental glomerulosclerosis (FSGS), hypertensive nephropathy, and non-diabetic ESRD among African and Hispanic Americans (Behar et al., 2010, Freedman et al., 2009a, Freedman et al., 2009b, Kao et al., 2008, Kopp et al., 2008). This association was not replicated among American Indians, a fact that could be partly explained by differences in the prevalence of risk factors for CKD between the populations (Franceschini et al., 2010).

Among individuals of European ascent, MYH9 polymorphisms have been linked to kidney function, non-diabetic and diabetic nephropathy, and idiopathic FSGS (Cooke et al., 2012, Kao et al., 2008, O'Seaghdha et al., 2011, Pattaro et al., 2009). Our objective was to define the effect of common MYH9 SNPs on renal function in a Spanish cohort of healthy elderly individuals.

Section snippets

Study population and data collection

This study was approved by the Ethical Committee of Hospital Universitario Central de Asturias (HUCA) and all the participants signed an informed consent. The RENASTUR was a cross-sectional study to evaluate the association between gene polymorphisms and renal function in elderly people. A total of 592 individuals aged 55–85, all Caucasian, non-related, and from the region of Asturias (Northern Spain, total population one million), were randomly chosen from the general population in the period

Results

Table 1 summarizes the main characteristics in the whole RENASTUR cohort, and in those with eGFR < 60 (n = 77) and ≥ 60 (n = 515) ml/min/1.73 m2. The genotype frequencies for the two MYH9 SNPs did not deviate from Hardy–Weinberg equilibrium in the two groups.

In the univariate analysis the next variables were significantly associated with an eGFR < 60: age (p < 0.001), male (p = 0.04), type 2 diabetes (p < 0.001), total cholesterol (p = 0.03), LDL-cholesterol (p = 0.05), and MYH9 rs3752462 T allele (dominant effect,

Discussion

CKD is a major cause of morbidity and mortality, and is thus considered an important community health problem. According to the EPIRCE study approximately 10% of the Spanish adult population had some degree of CKD (Otero et al., 2010). This was in agreement with our findings in the RENASTUR cohort, with 10% of the participants showing an eGFR < 60 ml/min/1.73 m2. The search for markers associated with CKD is important to identify individuals at risk for ESRD and cardiovascular events, which could

Financial disclosure

All the authors declare that they have no conflicts of interest related with this work.

Contributorship

All the authors contributed to this work by recruiting the population cohort (S.T., K.M., M.I.R., F.O., B.D., R.M., E.S., J.A.) or performing the genetic and statistical analysis (B.T., J.G., E.C., V.A.).

Acknowledgments

This work was supported by grant Red de Investigación Renal-REDINREN, and Fundación Investigación Científica y Técnica (FICYT)–European FEDER funds. This work was partly supported by grant FIS PI10/01971 (F.O.).

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