Xiyang Zhang

MMP-3 and MMP-8 single-nucleotide polymorphisms are related to alcohol-induced osteonecrosis of the femoral head in Chinese males

Our study investigated the association between MMP-3 and MMP-8 single-nucleotide polymorphisms (SNPs) and alcohol-induced osteonecrosis of the femoral head (ONFH) in 695 Chinese males (299 cases and 396 control subjects). The minor allele of MMP-3 rs650108 was associated with a 0.78-fold decrease in alcohol-induced ONFH risk in the allelic model (95% CI = 0.63-0.97, P = 0.026). In the genetic model adjusted for age, rs650108 was associated with decreased risk of alcohol-induced ONFH in the dominant model (OR = 0.68, 95% CI = 0.49-0.95, P = 0.022) and log-additive model (OR = 0.78, 95% CI = 0.63-0.98, P = 0.030); MMP-8 rs11225394 was associated with increased risk in the codominant model (OR = 1.72, 95% CI = 1.15-2.58, P= 0.010), dominant model (OR = 1.67, 95% CI = 1.12-2.48, P = 0.012), over-dominant model (OR = 1.73, 95% CI = 1.16-2.59, P = 0.007) and log-additive model (OR = 1.57, 95% CI= 1.07-2.32, P = 0.022); and MMP-8 rs2012390 was associated with decreased risk in the dominant model (OR = 0.72, 95% CI = 0.53-0.97, P = 0.032) and log-additive model (OR = 0.77, 95% CI = 0.60-0.98, P = 0.035). Haplotype analysis showed that the CGATATGT sequence mediated decreased alcohol-induced ONFH risk (OR = 0.75, 95% CI = 0.57-0.97, P = 0.029). Therefore, among Chinese males, MMP-3 rs650108 and MMP-8 rs2012390 decrease alcohol-induced ONFH risk and MMP-8 rs11225394 increases it. Further study is needed to validate our conclusion.

Genotype‑phenotype analysis of CYP2C19 in the Tibetan population and its potential clinical implications in drug therapy.

Cytochrome P450 2C19 (CYP2C19) is a highly polymorphic gene, it codes for a protein responsible for the metabolism of multiple clinically important therapeutic agents. However, there is currently no available data on the distribution of CYP2C19 mutant alleles in the Tibetan population. The aim of the present study was to identify different CYP2C19 mutant alleles and determine their frequencies, along with genotypic frequencies, in the Tibetan population. The whole CYP2C19 gene was amplified and sequenced in 96 unrelated, healthy Tibetans from the Tibet Autonomous Region of China, the promoter region, exons, introns and the 3′-UTR were screened for genetic variants. Three novel genetic polymorphisms in CYP2C19 were detected among a total of 27 different mutations. The allele frequencies of CYP2C19*1A, *1B, *2A, *3A and *17 were 50, 28.13, 15.10, 5.21 and 1.56%, respectively. The most common genotype combinations were CYP2C19*1A/*1B (56.25%) and *1A/*2A (30.21%). One novel non-synonymous mutation (Asn to Lys) in CYP2C19 was identified, and this mutation was predicted to be intolerant and benign by SIFT and PolyPhen-2, respectively. The observations of the present study may have important clinical implications for the use of medications metabolized by CYP2C19 among Tibetans.

Genetic polymorphisms in TNIP1 increase the risk of gastric carcinoma

The distribution and levels of TNIP1 in malignant and normal gastric mucosa are different, but it is not known whether TNIP1 polymorphisms are related to gastric carcinogenesis. To assess the association between four TNIP1 SNPs (rs3792792, rs4958881, rs7708392, rs10036748) and carcinogenesis, we used Sequenom Mass-ARRAY technology to determine the genotypes of 302 gastric carcinoma patients and 300 healthy controls in a Northwest Chinese Han population. These data were then compared using the Chi-square test/Fishers exact test, genetic model analysis, and haplotype analysis. Odds ratios (OR) and 95% confidence intervals (CI) were used to evaluate the correlation. We observed that patients with the “G” allele of rs7708392 and the “C” allele of rs10036748 showed an increased risk of gastric carcinoma (OR= 1.335, 95%CI: 1.021-1.745, P= 0.035; OR= 1.358, 95%CI: 1.039-1.774, P= 0.025, respectively). Conversely, the haplotype “CT” of TNIP1 (rs7708392-rs10036748) may act as a genetic protective factor for gastric carcinoma (adjusted OR= 0.731, 95%CI: 0.552-0.970, P= 0.030). Our results are the first to suggest that genetic variation in TNIP1 gene is associated with gastric carcinoma, though, this finding must be confirmed in other populations with larger sample size.

Genetic variants in TERT are associated with risk of gastric cancer in a Chinese Han population

Telomerase reverse transcriptase (TERT) is a gene within the cancer susceptibility region located at Chr5p15.33, which is associated with multiple cancer types. In this study, we validated the association between TERT polymorphisms and gastric cancer (GC) risk with a case-control study in a Chinese Han population. A total of 302 GC patients and 300 control individuals were recruited. We identified three single nucleotide polymorphisms (SNPs) in TERT that were associated with GC. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in logistic regression models after adjusting for age and gender to assess the association. The minor alleles of three SNPs were associated with increased GC risk inallelic model analysis. For two of the SNPs, rs10069690 and rs2853676,, the dominant and additive model frequencies were higher in GC cases compared to controls. Further haplotype analysis revealed a protective effect of haplotype “CG” of the TERT gene, while the haplotype “TA” increased GC risk.Our resultsprovide new evidence for the association between TERT and GC susceptibility in the Chinese Han population.

Telomere length related gene ACYP2 polymorphism is associated with the risk of HAPE in Chinese Han population

High altitude pulmonary edema (HAPE) is a type of pneumonedema that mostly occurs under conditions such as high altitude, rapid ascent and hypoxia, amongst others. The ACYP2 polymorphism is suggested to be associated with mean telomere length, and telomere length is significantly longer at a moderate attitude than at sea‐level or at simulated high attitude. The present study aimed to determine whethher there is any association between ACYP2 polymorphism and the risk of HAPE.