Evaluation of MMP1 and MMP3 gene polymorphisms in exfoliation syndrome and exfoliation glaucoma

Purpose: To investigate possible genetic associations of matrix metalloproteinase-1 (MMP1) and MMP3 gene polymorphisms with exfoliation syndrome (XFS) with (XFS/+G) and without (XFS/-G) glaucoma in a cohort of Greek patients. Methods: A total of 182 unrelated Greek patients with XFS, including 92 patients with XFS/+G, and 214 unrelated age- and gender-matched controls were enrolled in the study. MMP1-1607 1G/2G (rs1799750) and MMP3-1171 5A/6A (rs3025058) polymorphisms were determined using standard PCR/restriction fragment length polymorphism methods. Differences in allele and genotype distributions were analyzed using logistic regression. Results: The distribution of genotypes and alleles in MMP1 and MMP3 polymorphisms was not significantly different between cases with exfoliation syndrome, with or without glaucoma, and controls. However, the allele contrast for the MMP1 variant showed a trend for a significant association with XFS/-G (Odds Ratio=1.47 [1.03-2.10]), since after correction for multiple comparisons, this association was no longer statistically significant. Conclusions: Our study provided some evidence of a possible role of the MMP1 variant in the development of exfoliation syndrome in Greek patients

Generalized distributions of order k associated with success runs in Bernoulli trials

In a sequence of independent Bernoulli trials, by counting multidimensional lattice paths in order to compute the probability of a first-passage event, we derive and study a generalized negative binomial distribution of order k, type I, which extends to distributions of order k, the generalized negative binomial distribution of Jain and Consul (1971), and includes as a special case the negative binomial distribution of order k, type I, of Philippou et al. (1983). This new distribution gives rise in the limit to generalized logarithmic and Borel-Tanner distributions and, by compounding, to the generalized Pólya distribution of the same order and type. Limiting cases are considered and an application to observed data is presented

MTHFR gene polymorphisms and response to chemotherapy in colorectal cancer: a meta-analysis

Aims: Pharmacogenetic studies investigating the relationship between MTHFR gene polymorphisms and response to fluorouracil-based chemotherapy in patients with colorectal cancer have produced inconclusive results. In an attempt to interpret these results, a meta-analysis of all eligible studies published up until January 2009 was carried out. Materials & methods: A total of ten studies relating MTHFR C677T and six studies relating MTHFR A1298C to the response to chemotherapy in patients with colorectal cancer were included in the meta-analysis and random effects pooled odds ratios were estimated. The heterogeneity between studies, the sources of potential bias and the consistency of genetic effects across ethnicities were explored. Cumulative and recursive cumulative meta-analyses were also performed. Results: For both the C677T and A1298C polymorphisms, the main analysis revealed nonsignificant heterogeneity and a lack of association under the allele contrast, the recessive and dominant models. The subgroup analysis by ethnicity did not change this pattern of results. The lack of stability of the relative change of odds ratio in the recursive cumulative meta-analysis for both polymorphisms indicated the need for more evidence to support a definite lack of association. There was no differential magnitude of the effect in large versus small studies. Conclusion: The available evidence indicates that MTHFR C677T and A1298C gene polymorphisms cannot be considered as reliable predictors of response to fluorouracil-based chemotherapy in patients with colorectal cancer

Methylenetetrahydrofolate reductase gene polymorphism as a risk factor for diabetic nephropathy: a meta-analysis

Investigations into the association between diabetic nephropathy (DN) and MTHFR C677T gene polymorphism in several case-control studies has yielded contradictory results. To shed light on these inconclusive findings, a meta-analysis of all available studies relating the C677T polymorphism to the risk of developing DN was conducted. The PubMed database was searched, and case-control studies investigating the association between MTHFR C677T gene polymorphism and DN were included in the meta-analysis. The meta-analysis included 15 studies, of which 8 involved Caucasians and 5 East Asians; 11 studies involved subjects with type 2 diabetes and 4 with type 1 diabetes. The main analysis (all studies) revealed significant heterogeneity between the studies (P-Q < 0.01) and a marginal association between the 677T allele and the risk of developing DN; the random effects (RE) pooled odds ratio (OR) was 1.30 (1.03-1.64). However, the sensitivity analysis (exclusion of studies not in Hardy-Weinberg equilibrium) produced non-significant results. The recessive model derived significant results in main analysis [fixed effects (FE) OR = 1.32 (1.10-1.58), P (Q) = 0.27], and in type 2 diabetes [FE OR = 1.30 (1.06-1.60), P-Q = 0.38]. The additive model produced significant association in main analysis [RE OR = 1.65 (1.13-2.42), P-Q < 0.01] in Caucasians [FE OR = 1.48 (1.11-1.98), P-Q = 0.17] and in type 2 diabetes [RE OR = 1.65 (1.03-2.67), P-Q < 0.01]. However, sensitivity analysis diminished the significant results in type 2 diabetes. There is no differential magnitude of effect in large versus small studies. In conclusion, although there is some evidence of association between MTHFR C677T gene polymorphism and DN, the above findings reinforce the need for further and more rigorous association studies

Endothelial nitric oxide synthase gene polymorphisms and diabetic nephropathy: A HuGE review and meta-analysis

Candidate-gene association studies that examined the association between polymorphisms of endothelial nitric oxide synthase (NOS3) gene (G894T, 4b/a, and T786C) and diabetic nephropathy or diabetes leading to severe nephropathy produced inconclusive results. Thus, a meta-analysis of all candidate-gene association studies with endothelial nitric oxide synthase genotyping (7401 cases and 8046 controls) was conducted. Other study designs. such as family-based association studies and genome-wide linkage and association studies were also reviewed for supportive evidence of implication of endothelial nitric oxide synthase gene in diabetic nephropathy. The meta-analysis showed that G894T is significantly associated with diabetic nephropathy and diabetes leading to severe nephropathy in type 2 diabetics and in East Asians, respectively. Concerning the 4b/a polymorphism and its relationship to diabetes leading to severe nephropathy, a significant association was shown for East Asians. Heterogeneity between studies was in general high. There was no differential magnitude of effect in large versus Small studies. One genome-wide linkage scan provided evidence of linkage nearby the endothelial nitric oxide synthase locus. Studies exploring gene and environment interactions with endothelial nitric oxide synthase polymorphisms may help understand better the genetics of diabetic nephropathy. Genet Med 2009:11(10):695-706