|?|| (A;A) (A;G) (G;G) ||28|
rs10868025 is associated with diabetic nephropathy, a kidney disease resulting from poorly managed diabetes and genetic factors. When a person has diabetic nephropathy, excess levels of blood sugar cause damage to blood vessels within the nephrons, which are filtering units within the kidneys. Diabetic nephropathy is the number one cause of long-term kidney failure and end-stage kidney disease in the United States .
Some of the first evidence for a genetic factor in the development of this disease was published in a New England Journal of Medicine paper in 1989 [PMID 2710189]. However, causal variants have yet to be identified [PMID 16101480]. This could potentially be due to different variants being responsible for different stages of the disease [PMID 15822051].
In a study, researchers found an association between rs10868025 (9q85.4) and diabetic nephropathy [PMID 19252134]. In this study, genome wide scans were first performed on the GoKinD collection with 885 case and 820 control subjects on an Affymetrix array, and putative markers were then screened in a follow-up study looking for association between these markers and time-to-onset of nephropathy in the DCCT/EDIC data, which contained 132 cases of nephropathy and used an Illumina array. In the former analysis, the odds ratio for rs10868025 was 1.45, with a 95% confidence interval of (1.25-1.67) and a p-value of 5e-7, though this was not low enough to achieve genome-wide significance in the study (needed 1.4e-7). G is the non-risk allele and A is the risk allele. In the latter analysis, rs13289150 (r^2 = 1.0 with rs10868025) was used instead of rs10868025 and found to be significantly associated with time-to-onset of nephropathy (p-value = 0.05).
While rs10868025 is not in a gene, it is located near the FRMD3 gene, which is part of the 4.1 protein ezrin, radixin, moesin (FERM) domain. It was found in this study that cell lines relevant to diabetic nephropathy express this gene. FRMD3 encodes the 4.1O protein, which contains a FERM domain that is necessary for maintaining the integrety of the cellular membrane.
[PMID 20460425] Replication study for the association between four Loci identified by a genome-wide association study on European American subjects with type 1 diabetes and susceptibility to diabetic nephropathy in Japanese subjects with type 2 diabetes.
[PMID 21911749] CPVL/CHN2 genetic variant is associated with diabetic retinopathy in Chinese type 2 diabetic patients.