Abstract
ObjectiveThough single nucleotide polymorphisms (SNPs) in the non-muscle myosin gene (MYH9) have been reported to explain most of the excess risk of nondiabetic chronic kidney disease (CKD), in African-Americans, some studies have also shown associations with diabetic end-stage renal disease. We investigated the association of MYH9 SNPs with renal traits in a mixed-ancestry South African population prone to diabetes.Research Design and MethodsThree SNPs known to be associated with CKD (rs4821480, rs5756152 and rs12107) were genotyped using Taqman assay in 716 adults (198 with diabetes) from the Bellville-South community, Cape Town. Glomerular filtration rate was estimated (eGFR) and urinary albumin/creatinine ratio (ACR) assessed. Multivariable regressions were used to relate the SNPs with renal traits.ResultsMean age was 53.6 years, with the expected differences observed in characteristics by diabetic status. Significant associations were found between rs575152 and serum creatinine, and eGFR in the total population, and in diabetic participants (all p≤0.003), but not in non-diabetics (all p≥0.16), with significant interactions by diabetes status (interaction-p≤0.009). The association with ACR was borderline in diabetic participants (p = 0.05) and non-significant in non-diabetics (p = 0.85), with significant interaction (interaction p = 0.02). rs12107 was associated with fasting-, 2-hour glucose and HbA1c in diabetic participants only (interaction-p≤0.003), but not with renal traits.ConclusionMYH9 SNPs were associated with renal traits only in diabetic participants in this population. Our findings and other studies suggest that MYH9 may have a broader genetic risk effect on kidney diseases.
Highlights
The characterization of the associations between chronic kidney diseases (CKD) and polymorphisms on chromosome 22q12, namely MYH9 and APOL1 was an immense breakthrough for population-based genetic studies of CKD [1,2]
Significant associations were found between rs575152 and serum creatinine, and estimated glomerular filtration rate (eGFR) in the total population, and in diabetic participants, but not in non-diabetics, with significant interactions by diabetes status
MYH9 single nucleotide polymorphisms (SNPs) were associated with renal traits only in diabetic participants in this population
Summary
Compared with nondiabetics, participants with diabetes were older (59.9 vs 51.3 years, p,0.0001), had higher body mass index (31.7 vs 29.1 kg/m2, p,0.0001), higher waist-to-hip ratio (0.92 vs 0.87, p,0.0001), higher systolic blood pressure (129 vs 121 mmHg, p,0.0001) and included more individuals with hypertension (65.1% vs 34.0%, p,0.0001) They were more likely to have higher urinary albumin/creatinine ratio (median: 1.06 vs 0.62, p,0.0001) and lower estimated glomerular filtration rates based on either the MDRD, or CKD-EPI formulae (both p#0.01), Table 1. Association between SNPs within MYH9 and other Traits The associations of participants’ quantitative traits known to be related with CKD (including systolic blood pressure, fasting and 2hour glucose and HbA1c) and the three SNPs were assessed in age, sex, ACR and diabetes adjusted regression models and after stratification by diabetes status (Table 3). None of the SNPs was associated with systolic blood pressure (Table 3)
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