Background: The aim of this study was to explore the associations between the prevalence of chronic kidney disease (CKD) and polymorphisms in the genes encoding matrix metalloproteinases (MMPs) and tissue inhibitor of matrix metalloproteinases (TIMPs). MMPs degrade extracellular matrix proteins in the glomerulus, and play important roles in kidney disease progression. Methods: DNA samples from 3,309 subjects aged 35–69 years were genotyped for 10 potentially functional polymorphisms in MMP and TIMP genes. The prevalence of CKD (estimated glomerular filtration rate <60 ml/min/1.73 m²) was compared among the genotypes. Results: The prevalence of CKD decreased significantly with the number of minor alleles in MMP9 C–1562T (odds ratios (ORs) 0.77 for CT and 0.65 for TT compared with CC; p for trend = 0.023) and MMP9 R668Q (ORs, 0.79 for RQ and 0.64 for QQ compared with RR; p for trend = 0.024). The haplotype MMP9 –1562T/279R/668Q showed a reduced risk for CKD compared with the most common –1562C/279R/668R (OR 0.77, p = 0.008), and the genotype combination –1562TT/ 279RR/668QQ showed a halved risk for CKD compared with major allele homozygous –1562CC/279RR/668RR (OR 0.53, p = 0.091). Conclusion: The potentially functional polymorphisms of MMP9 were associated with the prevalence of CKD in a large Japanese population. These genotypes have been reported to increase MMP9 expression, supporting the hypothesis that MMP-9 has a protective role in the progression of kidney diseases.

BackgroundInflammatory gene polymorphisms are potentially associated with atherosclerosis risk, but their age-related effects are unclear. To investigate the age-related effects of inflammatory gene polymorphisms on arterial stiffness, we conducted cross-sectional and 5-year follow-up studies using the cardio-ankle vascular index (CAVI) as a surrogate marker of arterial stiffness.MethodsWe recruited 1850 adults aged 34 to 69 years from the Japanese general population. Inflammatory gene polymorphisms were selected from NF-kB1, CD14, IL-6, IL-10, MCP-1, ICAM-1, and TNF-α. Associations of CAVI with genetic and conventional risk factors were estimated by sex and age group (34–49, 50–59, and 60–69 years) using a general linear model. The association with 5-year change in CAVI was examined longitudinally.ResultsGlucose intolerance was associated with high CAVI among women in all age groups, while hypertension was associated with high CAVI among participants in all age groups, except younger women. Mean CAVI for the CD14 CC genotype was lower than those for the TT and CT genotypes (P for trend = 0.005), while the CD14 polymorphism was associated with CAVI only among men aged 34 to 49 years (P = 0.006). No association of the other 6 polymorphisms with CAVI was observed. No association with 5-year change in CAVI was apparent.ConclusionsInflammatory gene polymorphisms were not associated with arterial stiffness. To confirm these results, further large-scale prospective studies are warranted.

Aim: Observational studies have reported that elevated homocysteine (Hcy) levels are associated with the risk of cardiovascular disease (CVD). However, interventions that lower Hcy do not provide a corresponding risk reduction. Therefore, the causal role of Hcy in CVD remains unclear. This 5-year prospective study investigated the associations of Hcy levels, folate intake, and host factors with arterial stiffness among the general Japanese population. Methods: We prospectively recruited 658 participants (40 -69 years old) from the general population during regular health checkup examinations. Arterial stiffness was evaluated using the cardio-ankle vascular index (CAVI) at baseline and the 5-year follow-up. Folate intake was estimated using a structured questionnaire. Genotyping was used to evaluate the MTHFR C677T and MS A2756G gene polymorphisms. Ultrafast liquid chromatography was used to measure total plasma Hcy levels. Association between these variables and CAVI values was evaluated using general linear regression and logistic regression models that were adjusted for atherosclerosis-related factors.