Alternative titles; symbols
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 7q21.3 | {Microvascular complications of diabetes 5} | 612633 | 3 | PON1 | 168820 |
A number sign (#) is used with this entry because of evidence that susceptibility to microvascular complications of diabetes-5 is associated with variation in the PON1 gene (168820) on chromosome 7q21.3.
For a discussion of genetic heterogeneity of susceptibility to microvascular complications of diabetes, see MVCD1 (603933).
Kao et al. (1998) analyzed the L55M polymorphism in the PON1 gene (168820.0002), which they designated M54L, in 80 patients with diabetic retinopathy and 119 controls, and found a significantly higher allelic frequency of the leu55 polymorphism in the group with retinopathy than in the group without retinopathy (73% vs 57%, p less than 0.001).
Brophy et al. (2001) presented evidence that the L55M effect of lowered activity is not due primarily to the amino acid change itself but to linkage disequilibrium with the -108 regulatory region polymorphism (168820.0003). The -108C/T polymorphism accounted for 22.8% of the observed variability in PON1 expression levels, which was much greater than that attributable to other PON1 polymorphisms.
Kao et al. (2002) analyzed the L55M (M54L) PON1 polymorphism and the C311S PON2 polymorphism (602447.0001) in 372 adolescents with type 1 diabetes (222100) who were also assessed for diabetic retinopathy and albumin excretion rate. The authors confirmed the increased susceptibility to diabetic retinopathy with the PON1 leu/leu genotype (odds ratio, 3.4; p less than 0.0001) independent of age, duration of disease, and cholesterol, and found that the PON2 ser/ser genotype was significantly more common in patients with microalbuminuria (odds ratio, 4.72; p less than 0.0001). The authors also observed strong linkage disequilibrium between PON2 ser311 and PON1 leu55 that was greater in those without either complication, suggesting that retinopathy and nephropathy may have distinct genetic susceptibility.
Brophy, V. H., Jampsa, R. L., Clendenning, J. B., McKinstry, L. A., Jarvik, G. P., Furlong, C. E. Effects of 5-prime regulatory-region polymorphisms on paraoxonase-gene (PON1) expression. Am. J. Hum. Genet. 68: 1428-1436, 2001. [PubMed: 11335891] [Full Text: https://doi.org/10.1086/320600]
Kao, Y., Donaghue, K. C., Chan, A., Bennetts, B. H., Knight, J., Silink, M. Paraoxonase gene cluster is a genetic marker for early microvascular complications in type 1 diabetes. Diabet. Med. 19: 212-215, 2002. [PubMed: 11918623] [Full Text: https://doi.org/10.1046/j.1464-5491.2002.00660.x]
Kao, Y.-L., Donaghue, K., Chan, A., Knight, J., Silink, M. A variant of paraoxonase (PON1) gene is associated with diabetic retinopathy in IDDM. J. Clin. Endocr. Metab. 83: 2589-2592, 1998. [PubMed: 9661650] [Full Text: https://doi.org/10.1210/jcem.83.7.5096]