Genetic association analyses and meta-analysis of Dynorphin-Kappa Opioid system potential functional variants with heroin dependence.

Prodynorphin (PDYN) binds to k-opioid receptors (KOPr; encoded by OPRK1) and is known to regulate dopaminergic tone, making this system important for drugs addiction. Dynorphin (Dyn)/KORr system are powerful effectors of stress-induced alterations in reward processing and dysphoric states. Thus, We identified 11 potential functional SNPs and one variable number of tandem repeat (VNTR) in this system, performed a case-control association analysis, investigated particular disease phenotypes, assessed the joint effect of variants in two genes, carried out a meta-analysis to analyze the association between this VNTR and Heroin dependence (HD) risk. Eleven single-nucleotide polymorphisms (SNPs) were genotyped using SNaPshot SNP technology. Participants included 566 healthy controls and 541 patients with HD. We found that PDYN polymorphisms modulate the susceptibility to HD. An increased risk of HD was significantly associated with H alleles of PDYN VNTR (χ2 = 10.824, p = 0.001, OR = 1.419, 95% CI = 1.151-1.748). In addition, the results revealed the patients with the HH genotype showed greater number of withdrawal instances (F(2538) = 7.987, p = 0.0004) compared to the patients with the LL genotype. The Meta-analysis showed the pooled effect of the H allele at this locus is a risk factor for HD in Chinese Han. Gene-gene interaction analysis indicated strong interactions between PDYN rs3830064, 68-bp VNTR and OPRK1 rs16918842, rs3802279. These findings support the important role of PDYN polymorphism in HD, and may guide future studies to identify genetic risk factors for HD.

Polymorphisms in the vascular endothelial growth factor gene associated with recurrent spontaneous miscarriage.

OBJECTIVE: To evaluate the association between the vascular endothelial growth factor (VEGF) polymorphism and the risk of recurrent spontaneous miscarriage (RSM). METHODS: The participants enrolled included 227 RSM patients and 232 women with normal fertility. We examined the potential association between RSM and 13 single nucleotide polymorphisms (rs699947, rs1570360, rs2010963, rs833068, rs833069, rs3024997, rs3024998, rs3025000, rs3025006, rs3025010, rs3025020, rs3025030 and rs3025039) of VEGF gene using the MassARRAY system. RESULTS: The results showed that rs3025020 located at intron 6 of VEGF gene was significantly associated with RSM (χ(2 )= 12.6385, p = 0.0004, odds ratio (OR) = 1.6109, 95% confidence interval (CI) = 1.2377-2.0967). Another significant association was observed for rs3025039 located in the 3'-untranslated region of VEGF gene (χ(2 )= 9.7256, p = 0.0018, OR = 1.6492, 95% CI = 1.2023-2.2622). Furthermore, strong linkage disequilibrium was observed in three blocks (D' > 0.9), and significantly more T-G-C haplotypes (p = 0.0286) and fewer C-G-C haplotypes (p = 0.0006 after Bonferroni correction) residing in block 3 were found in RSM patients. CONCLUSION: These findings point to a role for VEGF gene polymorphisms in RSM, and may be informative for future genetic or neurobiological studies on RSM.