Validation of associations between ESR1 variants and breast cancer risk in Chinese cohorts.

Estrogen receptor-a (ER) protein plays a key role in breast carcinogenesis, and common genetic variants in the corresponding gene locus have been associated with breast cancer risk in different populations. Here, we analyzed estrogen receptor 1 (ESR1) associations in two hospital-based studies of patients from the south of China. Three single-nucleotide polymorphisms (SNPs; rs3757318, rs2046210, and rs3734805) in ESR1 were selected from previous genome-wide association study results and were genotyped using the Sequenom MassARRAY® iPLEX System in 845 breast cancer patients and 882 healthy controls. Association analysis based on unconditional logistic regression was carried out to determine the odds ratio (OR) and 95% confidence interval (95%CI) for each SNP. Stratified analyses according to the status of ER and progesterone receptor (PR) were also performed. Of the three SNPs, rs3757318 did not pass the Hardy-Weinberg equilibrium test and was excluded from the subsequent analysis. The other two SNPs (rs2046210 and rs3734805) were strongly associated with susceptibility to breast cancer. Allele T of rs2046210 and allele C of rs3734805 were risk alleles and the adjusted ORs were 1.348 (95%CI = 1.172-1.550, P = 0.0001) and 1.319 (95%CI = 1.144-1.522, P = 0.0001), respectively. Furthermore, the risk allele of rs2046210 gave negative results for ER and PR expression in an immunohistochemical test, with ORs of 0.602 (95%CI = 0.384-0.944, P = 0.027) and 0.532 (95%CI = 0.338-0.837, P = 0.006), respectively. Our study further supports associations between rs2046210 and rs3734805 and breast cancer risk in Chinese women.

Quantitative trait locus analysis of grape weight and soluble solid content.

A grapevine hybrid population was derived from a crossing of the early-maturing female parent cultivar '87-1' and the late-maturing male parent cultivar '9-22'. A total of 149 plants were selected from the hybrid population as the mapping population, and after sequence-related amplified polymorphism and simple-sequence repeat marker analysis were conducted we constructed molecular genetic maps of the parents. The molecular linkage map of '87-1' had 19 linkage groups that contained 188 markers, with an average interval of 5.7 cM and a total distance of 1074.5 cM; the '9-22' map had 19 linkage groups that contained 175 markers, with an average interval of 7.8 cM and a total distance of 1100.2 cM. The molecular linkage map of both parents had 19 linkage groups that contained 251 markers, with an average interval of 5.0 cM and a total distance of 1264.2 cM. We used the interval mapping method to conduct a quantitative trait locus (QTL) analysis of grape weight and soluble solid content of the mapping population. Six QTLs were related to grape weight, and the average contribution to the phenotypic variance was between 11.3 and 33.0%. Seven QTLs were related to soluble solid content, and the average contribution to the phenotypic variance was between 15.7 and 55.8%.

Short Communication: Genetic linkage map of Cucurbita maxima with molecular and morphological markers.

Cucurbita maxima is one of the most widely cultivated vegetables in China and exhibits distinct morphological characteristics. In this study, genetic linkage analysis with 57 simple-sequence repeats, 21 amplified fragment length polymorphisms, 3 random-amplified polymorphic DNA, and one morphological marker revealed 20 genetic linkage groups of C. maxima covering a genetic distance of 991.5 cM with an average of 12.1 cM between adjacent markers. Genetic linkage analysis identified the simple-sequence repeat marker 'PU078072' 5.9 cM away from the locus 'Rc', which controls rind color. The genetic map in the present study will be useful for better mapping, tagging, and cloning of quantitative trait loci/gene(s) affecting economically important traits and for breeding new varieties of C. maxima through marker-assisted selection.

Associations between INSR and MTOR polymorphisms in type 2 diabetes mellitus and diabetic nephropathy in a Northeast Chinese Han population.

We explored the associations of INSR and mTOR, 2 key genes in the insulin signaling pathway, and the susceptibility to type 2 diabetes mellitus and diabetic nephropathy. Three single-nucleotide polymorphisms (SNPs) (rs1799817, rs1051690, and rs2059806) in INSR and 3 SNPs (rs7211818, rs7212142, and rs9674559) in mTOR were genotyped using the Sequenom MassARRAY iPLEX platform in 89 type 2 diabetes patients without diabetic nephropathy, 134 type 2 diabetes patients with diabetic nephropathy, and 120 healthy control subjects. Statistical analysis based on unconditional logistic regression was carried out to determine the odds ratio (OR) and 95% confidence interval (95%CI) for each SNP. Combination analyses between rs2059806 and rs7212142 were also performed using the X(2) test and logistic regression. Among these 6 SNPs, 4 (rs1799817, rs1051690, rs7211818, and rs9674559) showed no association with type 2 diabetes mellitus or diabetic nephropathy. However, rs2059806 in INSR was associated with both type 2 diabetes mellitus (P = 0.033) and type 2 diabetic nephropathy (P = 0.018). The rs7212142 polymorphism in mTOR was associated with type 2 diabetic nephropathy (P = 0.010, OR = 0.501, 95%CI = 0.288- 0.871), but showed no relationship with type 2 diabetes mellitus. Combination analysis revealed that rs2059806 and rs7212142 had a combined effect on susceptibility to type 2 diabetes mellitus and diabetic nephropathy. Our results suggest that both INSR and mTOR play a role in the predisposition of the Han Chinese population to type 2 diabetic nephropathy, but the genetic predisposition may show some differences.

Association analysis of colorectal cancer susceptibility variants with gastric cancer in a Chinese Han population.

Evidence suggests that some genetic variants are risk factors for both colorectal cancer (CRC) and gastric cancer (GC). Thus, we selected 12 reported single nucleotide polymorphisms (SNPs) from genome-wide association studies of CRC and conducted this case-control study to assess the associations between these SNPs and the risk for GC in a southern Chinese population. All SNPs were genotyped in 249 individuals with GC and 292 healthy population-matched subjects using the Sequenom MassArray iPLEX System. Association analyses based on the c2 test and binary logistic regression were performed to determine the odds ratio (OR) and 95% confidence interval (95%CI) for each SNP. A stratified analysis by gender was also performed. Borderline significant associations were observed for rs4444235 (P = 0.070) and rs10411210 (P = 0.084), both fitting the overdominant model. The rs4444235 CT genotype showed a protective effect (OR = 0.72, 95%CI = 0.50-1.03), while the rs10411210 CT genotype was a risk factor (OR = 1.40, 95%CI = 0.96-2.05) as compared with the CC+TT genotype. In the female subgroup, the rs6983267 GT genotype (compared with TT, OR = 2.31, 95%CI = 1.07-4.99) and the rs10505477 CT genotype (compared with TT, OR = 2.36, 95%CI = 1.09-5.11) significantly increased the risk for GC. No significant association was detected for the other SNPs. These results provide evidence that known genetic variants associated with CRC risk may also confer risk for GC.

Selection pressures have driven population differentiation of domesticated and wild common carp (Cyprinus carpio L.).

Selection pressures are the principle evolutionary forces for the genetic differentiation of populations. Recent changes in selection pressures on mitochondrial DNA and microsatellite have been described in a wide variety of organisms. The common carp (Cyprinus carpio) has experienced strong selection pressure, in particular artificial selection, during its domestication. However, the contribution and extent of artificial selection in driving genome-wide population differentiation remain unclear. We investigated the genetic differentiation of 4 domesticated strains (Xingguo red common carp, Glass red common carp, Purse red common carp, and Jian common carp, which have been generated by artificial selection since 1970s) and 2 wild populations (Shishou section in Hubei and Yangzhou section in Jiangsu of the Yangtze River) of common carp in China by sequencing the mitochondrial DNA D-loop and by genotyping 10 microsatellite loci. It was found that the domesticated strains exhibited linkage disequilibrium within the population and less genetic variability, higher inbreeding coefficients (F(IS) = 0.101 vs 0.038), and higher genetic differentiation (F(ST) = 0.087 vs 0.001) than the wild populations, which indicates strong selection pressures in the process of domestication. Of the 10 loci, 5 appeared to be under positive directional selection in the domesticated strains, and all 10 loci in wild populations were potentially under balancing selection. We conclude that strong selection pressures, artificial selection in particular, have caused genetic differentiation between populations of domesticated and wild common carp.

Association of MHC class-III gene polymorphisms with ER-positive breast cancer in Chinese Han population.

Polymorphisms of the major histocompatibility complex (MHC) have been linked to many diseases, especially autoimmune disorders. Previous studies have shown that genetic variants in MHC class III are associated with breast cancer. To determine if there is an association between MHC class III and breast cancer risk in the Chinese Han population, we carried out a hospital-based case-control study in Guangdong and Jiangsu Provinces, including 216 histologically confirmed breast cancer patients and 216 healthy controls. Nine SNP markers distributed in the class III-coding region were detected using the Sequenom MassARRAY(®) iPLEX System. Deviation from Hardy-Weinberg equilibrium was observed for seven SNPs. There was no significant association between these seven SNP variants and breast cancer in these Chinese women (unconditional logistic regression analysis). However, chr6_31697494 at BAT2, one of the seven SNPs, was found to be significantly associated with both ER- and PR-positive breast cancer. In addition, both chr6_31911109 at C6orf48 and chr6_31975605 at ZBTB12, another two of the seven SNPs, show relevance with ER-positive breast cancer. In conclusion, this is the first evidence that genetic polymorphisms in the MHC class III region are significantly associated with ER-positive breast cancer in the Han Chinese population.

Association of DNMT1 and DNMT3B polymorphisms with breast cancer risk in Han Chinese women from South China.

Patterns of DNA methylation are established and maintained by a family of DNA methyltransferases (DNMTs). Aberrant promoter DNA methylation of tumor suppressor genes is found in breast cancer. Association studies between DNMT gene polymorphisms and breast cancer in various populations have reported inconsistent results. This study assessed the associations of single nucleotide polymorphisms (SNPs) in DNMT1, DNMT3A, DNMT3B, DNMT3L, and DNMT2 with breast cancer among Han Chinese women from South China. Sixteen SNPs (rs2114724, rs2228611, rs2228612, rs8101866, and rs16999593 in DNMT1; rs13420827, rs11887120, rs13428812, rs1550117, rs11695471, and rs6733301 in DNMT3A; rs2424908, rs2424913, and rs6087990 in DNMT3B; rs113593938 in DNMT3L, and rs11254413 in DNMT2) in 408 women with breast cancer and 469 controls were genotyped using a MassARRAY matrix-assisted laser desorption/ionization time-of-flight mass spectrometry platform. Two SNPs, rs16999593 in DNMT1 and rs2424908 in DNMT3B, were significantly associated with breast cancer risk. The heterozygous genotype CT of rs16999593 was associated with increased breast cancer risk [odds ratio (OR) = 1.60; 95% confidence interval (95%CI) = 1.20-2.14; P = 0.0052], whereas rs2424908 was associated with decreased risk (OR = 0.62; 95%CI = 0.46-0.84; P = 0.0061). Other DNMT polymorphisms showed no significant associations with breast cancer risk in the study population. Haplotype CGTC of rs2114724, rs2228611, rs8101866, and rs16999593 in DNMT1 differed significantly as a risk factor between the case and control groups (OR = 1.51; 95%CI = 1.18-1.93; P = 0.0012). The heterozygous genotypes of rs16999593 in DNMT1 and rs2424908 in DNMT3B were strongly associated with breast cancer risk.

Differences in H3K4 trimethylation in in vivo and in vitro fertilization mouse preimplantation embryos.

Trimethylation of lysine 4 at histone 3 (H3K4me3) is considered a marker of active transcription; it plays an important role in transcription reprogramming efficiency. We compared the levels of H3K4me3 in mouse preimplantation embryos from MII stage oocytes produced by in vivo and in vitro fertilization (IVF) using immunofluorescence histochemistry. IVF embryos were further treated with trichostatin A (a histione deacetylase inhibitor) to investigate the effect of histone acetylation on H3K4me3. We found higher levels of H3K4me3 in MII stage oocytes in metaphase chromosomes. The pattern of H3K4 trimethylation of in vivo embryos from zygote to blastocyst stages was similar to that of IVF embryos; however, the concentration of H3K4me3 was significantly higher in the in vivo fertilization embryos. The levels of H3K4me3 in the trichostatin A-treated groups were also significantly increased. We conclude that culture condition and environmental changes can cause histone modification and that the effect of these environmental conditions on epigenetic changes should be taken into consideration.

Genetic variants on 17q21 are associated with asthma in a Han Chinese population.

A genome-wide study has shown an association between SNPs located on 17q21 and asthma. Such associations have been identified in several populations, but little is known about the Han Chinese population. We conducted a case-control study in a Han Chinese population to investigate the relationship between SNPs located on 17q21 and asthma; 241 asthmatic patients and 212 healthy controls were recruited from the outpatient clinics of the Nanfang Hospital, Guangdong Province, southern China. We genotyped six SNPs (rs8067378, rs8069176, rs2305480, rs4795400, rs12603332, and rs11650680) located on 17q21 with the Sequenom MassARRAY iPLEX platform. For two of these six loci (rs2305480 and rs8067378), there was evidence of association with asthma, and there was a weak association of asthma with rs8069176. We confirm that genetic variants on 17q21 are associated with asthma in the Han Chinese population.