Aims: Although many studies have been performed on CYP2C19, most of them have mainly examined the effects of the defective alleles CYP2C19*2 and CYP2C19*3. A comprehensive search for genetic polymorphisms of the CYP2C19 gene in the Chinese Han population has rarely been conducted. The present study was designed to determine the genetic basis of CYP2C19 polymorphisms. Materials & Methods: We investigated the 5´-regulatory region, all the exons and their surrounding introns of the CYP2C19 gene in 400 unrelated healthy Chinese Han volunteers from four different geographical locations, namely Shanghai, Shantou, Shenyang and Xi’an, with a sample of 100 subjects in each population, using direct sequencing. Results: A total of 14 different CYP2C19 polymorphisms, including one novel variant (-2306G>A) in the enhancer region and a novel nonsynonymous one (905C>G, T302R) were identified. In addition, CYP2C19*1, *2, *3, *15 and *17 alleles showed frequencies of 69.7%, 24.7%, 3.3%, 1.2% and 1.2%, respectively, and CY...

Context: Telomeres are specialized chromatin structures located at the ends of eukaryotic chromosomes, and telomere length plays a clear role in various diseases. However, it is not known whether telomere length is related to polycystic ovary syndrome (PCOS). Objective: We hypothesized that leukocyte telomere length (LTL) plays an important role in the pathophysiology of PCOS. Design: We used an established and validated quantitative PCR technique to measure the mean LTL in a large sample of PCOS patients and controls. We used logistic regression and multiple linear regression to analyze the association of PCOS and several related clinical parameters with the age-adjusted ratio of the telomere repeat length to the copy number of a single-copy gene (T/S). Results: Individuals with PCOS (n = 698) exhibited significantly shorter LTLs than the controls (n = 611) after adjusting for age (0.764 ± 0.016 vs 0.876 ± 0.023; P = .001; odds ratio = 1.403; 95% confidence interval, 1.150–1.712). The mean telomere length in the leukocytes of PCOS patients was comparable to that of control individuals who were on average 6.16 years older. Individuals having shorter telomere lengths (middle and lowest tertile) had significantly higher disease risk than those having the longest telomere length (highest tertile) (odds ratio = 1.614; 95% confidence interval, 1.262–2.066; P = .0001) after adjusting for age. In addition, a significant correlation between the LTL and the level of dehydroepiandrosterone sulfate was observed in controls (r = −0.185; P = .01). Conclusion: We provide the first report that LTL is strongly associated with PCOS. This study suggests a new role for LTL in the pathophysiology of PCOS and might have important implications for our understanding of the etiology of the disease.

Cytochrome P450 3A4 (CYP3A4) is a major CYP enzyme in the liver and intestine. It is involved in the metabolism of over 50% of all drugs currently in use. The present study was designed to determine the genetic basis of CYP3A4 variability. Single nucleotide polymorphism (SNP) analysis of the CYP3A4 gene was performed on 60 healthy Chinese subjects consisting of 20 Han, 30 She and ten Dong subjects, using direct sequencing. Linkage disequilibrium, haplotype inference and Hardy-Weinberg equilibrium were also determined for these samples. A total of 20 SNPs were found in the CYP3A4 gene, including 11 known SNPs and nine novel SNPs. The known SNPs detected in our study were CYP3A4*1B, CYP3A4*1G, CYP3A4*10, CYP3A4*13, CYP3A4*14, CYP3A4*15, CYP3A4*17, CYP3A4*18, rs3091339, rs3091430 and rs28371761, and the novel SNPs were -658 A-->C, G27A (E10K), T48A, G14284A (G167D), A15623G (N191D), C15635A (L196I), T15656C (F203L), G14199A (intron 5) and C15566T (intron 6). The allelic frequencies found in our sample varied from 1-37%. The novel SNPs detected in the CYP3A4 gene suggest that the Chinese population has different patterns of allele frequency compared with other populations. Several SNPs were detected in the CYP3A4 gene. The study of genetic variants in CYP3A4 may have an important significance for the understanding of genotype and phenotype relationships.

The application of pharmacogenetics is currently one of the most promising developments in anti-psychotic treatment and is attracting more and more attention. Although risperidone belongs to the first-line atypical anti-psychotics, there have been relatively few risperidone pharmacogenetic studies, especially in Asian populations. We investigated the relationship between the C825T polymorphism of GBN3 (rs5443) and the —1019 C/G polymorphism of 5-HT₁A (rs6295) and response to risperidone treatment. One-hundred and thirty schizophrenia patients were recruited. They were treated with risperidone monotherapy for eight weeks. Clinical response was assessed on the Positive and Negative Syndrome Scale (PANSS) on the day of admission and was subsequently assessed after eight weeks following the treatment. Patients were genotyped for two functional polymorphisms: C825T of GBN3 (rs5443) and —1019 C/G of HT₁A (rs6295). Association tests between genotypes and percentage improvement in total PANSS scores, as well as positive symptom scores and negative symptom scores, were performed using analyses of variance (ANOVA). The —1019 C/G polymorphism of HT₁A (rs6295) was associated with negative symptom response to treatment. Patients with the CC genotype showed substantial improvement as regards negative symptom response ( F = 4.177, df = 2, P = 0.019), compared with the patients with the CG and GG genotypes. No association was observed between C825T of GBN3 (rs5443) and changes in PANSS scores. The results suggest that the —1019 C/G polymorphism (rs6295) in the 5-HT₁A gene may be a useful predictor of reduction in negative symptoms in schizophrenic patients treated with risperidone.