DNA repair gene XRCC3 variants are associated with susceptibility to glioma in a Chinese population.

The susceptibility to glioma is not well understood. It has been suggested that the X-ray cross complementing group 3 (XRCC3) gene influences the capacity to repair DNA damage, leading to increased glioma susceptibility. In this study, we evaluated the relationship between XRCC3 mutations and glioma risk. Genotypes were assessed in 389 Chinese glioma patients and 358 healthy controls. XRCC3 Thr241Met (rs861539) and 2 additional polymorphisms, rs3212112 (c.774+19T>G) and rs1799796 (c.562-14A>G), were directly sequenced. The frequency of the rs861539 T allele was significantly lower in the glioma group than in healthy controls [11.1 vs 17.7%, odds ratio = 0.62 (0.48-0.80), P < 0.001]; the frequencies of the CT or CT+TT genotypes differed between groups (18.5 vs 31%, 20.3 vs 33.2%, respectively). The frequency of the rs3212112 G allele was significantly higher in the glioma group than in healthy controls [15.8 vs 5.3%, odds ratio = 2.94 (2.07-4.17), P < 0.001]. The frequencies of the GT or TG+GG genotypes differed between groups (25.4 vs 7.8%, 28.5 vs 9.2%, respectively). This study demonstrates that the rs861539 and rs3212112 polymorphisms in the XRCC3 gene may influence the risk of glioma development in Chinese populations.

ACE gene sequence and nucleotide variants in IgA nephropathy.

INTRODUCTION: Association studies with single nucleotide polymorphisms (SNPs) have been contradictory. Haplotypes may be more helpful. With gene sequencing, all SNPs can be found for construction of haplotypes. METHODS: The ACE gene was sequenced in four healthy Chinese subjects and 20 patients with IgA nephropathy (IgAN) to observe if differences exist among SNPs and haplotypes. 20 patients on angiotensin 1-converting enzyme inhibitor/angiotensin receptor antagonist (ACEI/ATRA) therapy were then compared with another 20 patients not treated with ACEI /ATRA to determine their renal outcome in response to ACEI/ATRA therapy and whether their genetic profile of ACE gene could play a role in determining their outcome to ACEI /ATRA therapy and progression to end-stage renal failure (ESRF). RESULTS: IgAN patients had 53 variants, of which 17 were unique, whereas normal subjects had 38 variants, of which two were unique (p less than 0.005). No unique variant was a significant risk factor for IgAN. Significant genotype and allele frequency differences in five variants were observed between IgAN patients with renal impairment and those with ESRF (p less than 0.02). CONCLUSION: Our data suggests that at least in the ACE gene, haplotyping SNPs within a single gene seems to have no added advantage over genotyping the individual component SNPs. The D allele and haplotype 3 confer an adverse prognosis, while the I allele and haplotype 5 appear to be renoprotective. The data suggests that genotypes of the ACE gene are linked to certain haplotypes, which could influence IgAN patients' response to ACEI/ATRA therapy.