Age-related maculopathy susceptibility 2(ARMS2) was suggested to be associated with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) in multiple genetic studies in Caucasians and Japanese. To date, no biological properties have been attributed to the putative protein in nAMD and PCV. The complete genes of ARMS2 and HTRA1 including all exons and the promoter region were assessed using direct sequencing technology in 284 unrelated mainland northern Chinese individuals: 96 nAMD patients, 92 PCV patients and 96 controls. Significant associations with both nAMD and PCV were observed in 2 polymorphisms of ARMS2 and HTRA1 rs11200638, with different genotypic distributions between nAMD and PCV (p<0.001). After adjusting for rs11200638, ARMS2 rs10490924 remained significantly associated with nAMD and PCV (p<0.001). Then we overexpressed wild-type ARMS2 and ARMS2 A69S mutation (rs10490924) in RF/6A cells and RPE cells as in vitro study model. Cell proliferation, attachment, migration and tube formation were analyzed for the first time. Compare with wild-type ARMS2, A69S mutation resulted in a significant increase in proliferation and attachment but inhibited cell migration. Moreover, neither wild-type ARMS2 nor A69S mutation affected tube formation of RF/6A cells. There is a strong and consistent association of the ARMS2/HTRA1 locus with both nAMD and PCV, suggesting the two disorders share, at least partially, similar molecular mechanisms. Neither wild-type ARMS2 nor A69S mutation had direct association with neovascularisation in the pathogenesis of AMD.

Backgrounds and aims: Cholesterol 7α hydroxylase encoding by gene CYP7A1 is the initial and rate-limiting step in the classical bile acid synthesis pathway. Atorvastatin can markedly upregulate the mRNAs of bile acids synthetic enzymes CYP7A1 in the liver to increase fecal bile acid excretion. We tempt to investigate the association between a novel CYP7A1 polymorphism rs8192875 and reduction of lipid levels response to atorvastatin in Chinese patients with coronary artery disease.

ABSTRACT. Toll-like receptor 3 (TLR3) variants in mainland northern Chinese patients with polypoidal choroidal vasculopathy (PCV) and neovascular age-related macular degeneration (nAMD) were investigated. The complete genes of TLR3, including all exons and the promoter region, were assessed using direct sequencing technology of 284 unrelated mainland northern Chinese individuals: 96 nAMD patients, 92 PCV patients, and 96 controls. Six single TLR3 is not associated with nAMD and PCV nucleotide polymorphisms were identified: rs5743303, rs5743305, rs5743312, rs3775291, rs3775290, and rs6830345. The distribution of TLR3 genotypes for nAMD and PCV was not significantly different compared with normal controls. This study indicates that the TLR3 gene polymorphism is not associated with nAMD and PCV in northern Chinese patients.

Six single nucleoside polymorphism (SNP) sites were identified in the sequencing of the promoter and exons of the 5-HT2A receptor gene; however, genotypes and allele frequencies of the SNPs did not show significant differences between the patients and controls except the -1438G/A polymorphism. For SNP of -1438G/A, the A/A genotype was over-represented and the allele A was more frequent in the patients, while the G/A genotype was over-represented and the allele G was more frequent in the controls (p < 0.001, p = 0.005, respectively). In the patients, the A/A and G/A genotypes were over-represented in the subgroups with lowest nocturnal SaO(2) (LSaO(2)) ≤75% and LSaO(2) >75%, respectively (p = 0.006).

Aims/IntroductionThe objective of the present study was to investigate the effects of CYP2C9*3 polymorphisms on the therapeutic response to gliclazide in type 2 diabetes patients.Materials and MethodsA total of 746 incident type 2 diabetes patients were included in this study. After enrolment, patients went on 4‐week gliclazide monotherapy. Fasting plasma glucose was measured before and after treatment. Hypoglycemia episodes and lifestyle information were collected by weekly follow up. Genotyping of rs1057910 was carried out using the single base primer extension method. The t‐test, analysis of variance and chisquare‐test were used to evaluate the effects of rs1057910 alleles on the therapeutic response to gliclazide.ResultsAfter the therapy, fasting plasma glucose decreased significantly from 11.2 ± 2.7 mmol/L to 8.0 ± 2.2 mmol/L (P < 0.001). Patients with AC/CC genotypes of rs1057910 had a greater reduction of fasting plasma glucose (3.6 vs 3.0 mmol/L, P < 0.001; 31.4 vs 24.5%, P < 0.001) and a higher rate of treatment success (54.7 vs 37.5%, P < 0.001; 51.4 vs 32.3%, P < 0.001; 71.6 vs 48.3%, P < 0.001 for criterion 1, 2 and 3, respectively).ConclusionsThe present study showed that the polymorphism at rs1057910 significantly affected the therapeutic response of gliclazide in type 2 diabetes mellitus patients. The risk allele is associated with a greater decrease of fasting blood glucose and a higher rate of treatment success with gliclazide monotherapy.