The importance of ERα and ERβ gene polymorphisms in PCOS

Estrogens act through binding to estrogen receptor α (ERα) and β (ERβ). Studies in knockout mice have shown that the absence of ERα leads to the polycystic ovary syndrome (PCOS) phenotype. Furthermore, the expression of ERβ gene is lower in follicles derived from women with PCOS compared with healthy women. The aim of this study was to investigate the importance of ERα and ERβ gene polymorphisms in PCOS. A cohort of 180 women with PCOS and 140 healthy controls were recruited, and the PvuII and XbaI polymorphisms of ERα, as well as, the AluI and RsaI polymorphisms of ERβ were genotyped. No difference was found in the distribution of these polymorphisms between patients and healthy controls. However, in PCOS women, carriers of TC and TT genotypes of PvuII polymorphism had lower fasting glucose to insulin ratio compared with carriers of CC genotype (p = 0.029). In addition, the presence of AA genotype of XbaI polymorphism was associated with lower levels of follicle-stimulating hormone (FSH) compared with the presence of AG and GG genotypes (p = 0.03). The association of ERα polymorphisms with insulin resistance indices and FSH levels emphasizes the importance of ERα as a genetic modifier of the PCOS phenotype.     

Ⅱ型糖尿病患者APOA5-1131T/C基因多态性与血脂代谢和胰岛素抵抗的关系研究

为了探讨载脂蛋白A5基因(APOA5)-1131T/C多态性在中国镇江地区的频率分布及其与血浆脂质代谢和Ⅱ型糖尿病患者胰岛素抵抗的关系, 采用聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)结合琼脂糖凝胶电泳技术检测152例健康人及71例Ⅱ型糖尿病患者APOA5 -1131T/C基因型及等位基因频率分布, 同时采用生化方法测定所有研究对象的血脂、血糖和胰岛素水平。结果显示: 糖尿病组APOA5 -1131C等位基因频率显著高于对照组(0.430 vs 0.296, P = 0.006)。CC纯合子患糖尿病的风险是TT纯合子的3.75倍(OR = 3.75, 95% CI: 1.57~8.92), 且经Logistic回归分析, 校正年龄、BMI和血浆HDL-c、LDL-c及ApoB水平等其他混杂因素影响后, 这种差异仍具有显著性意义(OR = 2.70, 95%CI: 1.24 ~ 5.86)。糖尿病组C等位基因携带者TG水平显著高于非C等位基因携带者(P < 0.01), TC水平和LDL-c水平亦明显升高(P < 0.05)。但是在两组中, 不同基因型患者 胰岛素抵抗相关指标均无显示差异。提示APOA5-1131T/C单核苷酸多态性对人群血浆TG水平有影响, -1131C等位基因与血浆TG、TC和LDL-c水平增高有关, 但是与糖尿病患者胰岛素相关指标无关; APOA5 -1131C等位基因可能与人群糖尿病的发生相关联。     

湖羊、东湖杂种羊POMC基因外显子3单核苷酸多态性及其与生长性状的关联分析

阿黑皮素原(Pro-opiomelanocortin, POMC)在动物采食和能量平衡调控中发挥重要作用, 文章对绵羊POMC基因外显子3进行扩增和测序, 筛选多态性位点, 并分析多态位点与湖羊和东弗里生×湖羊杂种羊生长性状的相关性。测序后发现湖羊POMC基因外显子3有2个单碱基突变(g.273 T/C和g.456 G/A), 根据273位点处发生的T/C突变, 建立PCR-RFLP分析方法, 并对162只湖羊和130只东湖杂种羊进行检测分析。结果发现, 在湖羊群体中检测到TT(0.469)、TC(0.438)和CC(0.093)3种基因型, 而在东湖杂种羊群体中仅检测到TT(0.754)和TC(0.246)两种基因型。POMC基因外显子3的273位点多态性与生长性状的相关性研究结果显示：湖羊群体中CC基因型个体的2月龄断奶重、4月龄尻高及TC基因型个体4月龄体长和管围均显著高于TT型个体(P<0.05); CC基因型个体的4月龄重、6月龄重极显著高于TT和TC基因型个体(P<0.01); CC基因型个体的4月龄体高和体长极显著高于TT型个体(P<0.01), 且显著高于TC基因型个体(P<0.05)。此外, CC型个体的管围极显著高于TT基因型个体(P<0.01)。东湖杂种羊群体中TC基因型个体的2月龄断奶重、4月龄重及4月龄体高、体长、胸深和管围都显著高于TT型个体(P<0.05), TC型个体的6月龄重极显著高于TT型个体(P<0.01)。研究结果表明, POMC基因外显子3与绵羊生长性状相关, C等位基因对体重及体尺性状的增加更有利。该结果为进一步探讨POMC基因作为绵羊生长性状的辅助选育标记奠定了基础。     

Association between parathyroid hormone (PTH)/PTH-related peptide receptor gene polymorphism and the extent of bone mass reduction in primary hyperparathyroidism.

Genetic contributions to bone mineral density (BMD) and bone turnover are well known. In the present study, we analyzed the relationship between polymorphism of parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor gene existing in exon M7 and the clinical characteristics of primary hyperparathyroidism (pHPT). PTH/PTHrP receptor genotypes were analyzed in 92 pHPT patients by direct sequence to determine whether nucleotide 1417 of the cDNA was C or T. BMD levels at the lumbar spine and at the radius before and one year after parathyroidectomy, as well as serum levels of calcium, phosphorus, alkaline phosphatase (ALP) and intact PTH were measured. Although there were no significant differences in serum levels of calcium, phosphorus and intact PTH, ALP was significantly lower in the CT genotype compared with the TT genotype. BMD level at the radius was significantly higher in the CT genotype than in the CC genotype. Moreover, an increase in radial BMD one year after parathyroidectomy was significantly less in CT genotype than two other genotypes (CC, TT). The present study is the first to indicate that the polymorphism of PTH/PTHrP receptor gene is closely related to the extent of bone mass reduction in pHPT and that this polymorphism would be one of the genetic factors responsible for the severity of the pathological state of pHPT.     

Mitogen/extracellular signal-regulated kinase kinase-5 promoter region polymorphisms affect the risk of sporadic colorectal cancer in a southern Chinese population

Mitogen/extracellular signal-regulated kinase kinase-5 (MEK5), which belongs to a network of mitogen-activated protein kinase pathways, play a pivotal role in carcinogenesis. The purpose of this study was to investigate whether variants in the MEK5 gene promoter were involved in susceptivity of individuals to sporadic colorectal cancer (CRC). In the present hospital-based case-control study of 737 patients with sporadic CRC and 703 healthy control subjects in a southern Chinese population, the two polymorphisms of MEK5 promoter (i.e., rs7172582C>T and rs3743354T>C) were genotyped by TaqMan assay. There were significant differences between cases and controls in the genotype and allele distribution of the MEK5 gene rs3743354T>C polymorphism. The rs3743354 CC genotype was associated with a significantly decreased risk of CRC when compared with the TT genotype (adjusted odds ratios [ORs]=0.43; 95% confidence interval [CI], 0.24-0.77). Compared to the T allele, a significant correlation was detected between the presence of the C allele and decreased risk of CRC (adjusted OR=0.79; 95% CI, 0.61-0.94). The decreased risk of CRC associated with rs3743354 variant genotypes (i.e., CT+CC) was found in the smoker subgroup (adjusted OR=0.63; 95% CI=0.45-0.88). Further, environmental factors, including smoking and drinking, interacted with rs3743354C variant genotypes to reduce CRC risk. Western blot analysis showed that the levels of MEK5 protein in sporadic CRC neoplastic tissues and adjacent normal colorectal epithelium tissues were lower in the carriers of rs3743354 CC genotypes than that in those with rs3743354 TT genotypes or those with rs3743354 TC genotypes. However, no significant association was found between the rs7172582C>T polymorphism and risk of CRC. These data indicate that the rs3743354 polymorphism in the MEK5 promoter may affect the risk of developing CRC.     

Genetic Influence in Developmental Dysplasia of the Hip in Saudi Arabian Children Due to <Emphasis Type="Italic">GDF5</Emphasis> Polymorphism

Developmental dysplasia of the hip (DDH) is quite common among Saudi Arabian babies. With an objective to assess the presence of SNP rs143383 and the alleles in the GDF5 gene among patients with DDH, parents, and unaffected siblings, we undertook this case-controlled study. We collected and analyzed for a functional single nucleotide polymorphism (SNP) in the 5′-untranslated region of the GDF5 gene (rs143383), 473 blood samples, (100 patients, 200 parents, 73 siblings and 100 healthy controls. We determined the association between the patients’ genotype and their fathers’, mothers’ and siblings’ genotype through Chi-square analysis. The majority of those screened possessed the TC genotype, and 61.8% of patients and their fathers had the TT genotype. There was no association between patients’ and fathers’ genotype, P value?<?0.332, 95% CI (0.328–0.346), and between patients’ and mothers’, P?<?0.006, 95% CI (0.004–0.007). When considering DDH patients’ and the control group’s genotypes, the odds ratios of TT versus other combined (0.641?>?1) and CC versus other combined (0.474?<?1) revealed that the TT genotype has higher risk of developing DDH compared with the CC genotype. The 95 percent confidence interval of TT versus other combined and CC versus other combined is 0.932–2.891 and 0.208–1.078, respectively. For patients’ and fathers’ genotypes, the odds ratios of TT versus other combined (1.275?>?1) and CC versus other combined (0.815?<?1) indicate that the TT genotype has higher risk of exhibiting DDH compared to the CC genotype. For patients’ and siblings’ genotypes, the odds ratios of TT versus other combined (1.669) and CC versus other combined (1.048) specify that the TT genotype possesses higher risk of developing DDH compared with the CC genotype. Our study shows that there exists a relationship between GDF5 (SNP rs143383) and DDH in our population. Second, we found for the first time that the genotype TT and the T allele were overly expressed in the patients and the fathers. More studies on the confirmation of this genetic marker for DDH are called for.     

Analysis of VEGF gene polymorphisms and serum VEGF protein levels contribution in polycystic ovary syndrome of patients

Vascular endothelial growth factor (VEGF) is a well-known factor in reproductive function and contributes to the pathogenesis of polycystic ovary syndrome (PCOS). Genetic variations in VEGFA gene were suggested to contribute alterations in VEGF secretion and PCOS. This study evaluated the association of VEGFA SNPs with altered VEGF secretion level and PCOS among ethnically-matched control women. This prospective case–control study was conducted from 2016 to 2018 and comprised of 55 women with PCOS and 52 control subjects. ELISA was used to measure VEGF levels; and various other related bio chemicals whereas the genotyping of VEGFA variants was performed through the analysis of nine SNPs of VEGF. PRL, E2, PRGE testosterone and glucose level were found to be insignificantly different. The levels of FSH, LH, LH/FSH, TT, insulin, SHBG and HOMA-IR were significantly higher in the study group. Among the nine tested variants of VEGF SNPs, two SNPs rs3025020 and rs833061, consisted of TT (Recessive and Dominant homozygous, respectively) which were marginally higher in test. The SNP rs1570360 had significantly higher GG allele (32.73%) which was recessive homozygous. There was no significant difference observed in genotype frequencies related to higher value of VEGF. The genotype frequencies for the studied SNPs were in alignment with Hardy–Weinberg equilibrium (HWE). The mean serum VEGF levels got significantly increased in PCOS group. No significant association was found between VEGF genotypes and its serum levels. VEGF levels in rs699947 (AA-major homozygous), rs3025039 (CC-major homozygous) and rs833061 (TT & CC-major & minor homozygous) genotypes were significantly higher in PCOS. The study results evidently proved that the allelic variants in genes may be a factor for PCOS and VEGF serum levels with respect to few SNP variants only. These findings indicated that VEGF may be involved in PCOS status and confirmed the previous association between genetic variants in VEGF, serum level of VEGF protein and PCOS.

     

The relationship of the ESR1 gene polymorphisms with the presence of coronary artery disease determined by coronary angiography

Effects of estrogen on the cardiovascular system, mediated mainly by estrogen receptor type alpha (ER alpha), have been well-defined and specific polymorphisms in the ER alpha gene (ESR1) have been associated with several coronary heart diseases including coronary artery disease (CAD) in studies covering different populations. In the present study, we aimed to investigate whether there is an association between two of the known polymorphisms in the ESR1, named c.454-397T>C and c.454-351A>G, and CAD in a Turkish population. One hundred sixty eight patients with CAD and 99 patients without CAD were included in the study. The ESR1 c.454-397T>C and c.454-351A>G polymorphisms were studied by the conventional polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. While no association was found between the c.454-351A>G polymorphism and CAD, the c.454-397T>C genotype distributions were statistically significant independent of known risk factors between CAD-positive (CAD+) and CAD-negative (CAD-) groups (p = 0.001). TT genotype was more frequent in CAD- group than in CAD+ group, 22.2% and 4.8%, respectively. CC genotype was associated with increased risk of CAD (p = 0.001) compared to the TT genotype. When comparing the distribution of CC + TC genotypes to that of TT genotype in CAD+ and CAD- groups, the frequency of CC + TC genotypes showed a significant increase independent of known CAD risk factors in CAD+ subjects (p = 0.001). As a conclusion, a statistically significant relationship between the ESR1 c.454-397T>C polymorphism and CAD were found independent of known CAD risk factors in a Turkish population.     

Association Study between Polycystic Ovarian Syndrome and the Susceptibility Genes Polymorphisms in Hui Chinese Women

IntroductionPolycystic ovary syndrome (PCOS) is one of the most common endocrine-metabolic disorders. Evidence of familial aggregation analysis and different clinical traits among different regions and ethnicities indicated that the pathogenesis of PCOS is associated with multiple genetic and environmental factors. Our previous research had identified three susceptibility loci (rs2479106, DENND1A; rs13405728, LHCGR; rs13429458, THADA) for PCOS in Han Chinese women. The overall aim of this study was to investigate the relationship between three susceptibility gene polymorphisms and PCOS in Hui ethnic women.Methods151 patients with PCOS (case group) and 99 healthy women (control group) were recruited from the Reproductive Medicine Center of the General Hospital of Ningxia Medical University. Clinical data and serum hormone characteristics of case and control groups were collected and analyzed. The three susceptibility single-nucleotide polymorphisms have been replicated in both case and control groups. Gene polymorphisms were detected by direct sequencing after polymerase chain reaction.ResultsThe Body Mass Index, LH, LH/FSH ratio and total testosterone were significantly elevated in PCOS patients compared to control group (P<0.05). The frequencies of genotype and allele in rs13405728 were significantly different between the PCOS and the control groups (P<0.05). Of the SNP rs13405728, the PCOS cases with TT genotype stayed at a higher level of total testosterone, TG and LDL than those with the CC and CT genotypes. In contrary, there was no statistical difference between the two groups for SNP rs13429458 and rs2479106 (P>0.05).ConclusionThe present study suggested that the SNP rs13405728 in the LHCGR gene was associated with PCOS in Hui ethnic women, and its TT genotype characterized with higher level of TT, TG and LDL.     

Influence of BLK polymorphisms on the risk of rheumatoid arthritis

B cell lymphocyte kinase (BLK) encodes a member of the Src kinase family and thus may influence the proliferation and differentiation of cells. A single nucleotide polymorphism (SNP) located in the first intron of BLK has shown that the risk C allele of rs2248932 is associated with lower levels of messenger RNA expression of BLK. We hypothesized that this polymorphism may contribute to rheumatoid arthritis (RA) susceptibility. We studied BLK rs2248932 T/C gene polymorphisms in 329 patients with RA and 697 controls in a Chinese population. Genotyping was done using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). When the BLK rs2248932 TT homozygote genotype was used as the reference group, the CC genotype was associated with a significantly increased risk of RA. In the recessive model, when the BLK rs2248932 TT/TC genotypes were used as the reference group, the CC homozygote genotype was associated with a significantly increased susceptibility to RA. In stratification analyses, a significantly increased risk for RA associated with the BLK rs2248932 CC genotype was evident among younger patients, CRP-negative patients and anti-CCP-positive patients compared with the BLK rs2248932 TT/TC genotype. The risk was also significantly evident among RF-positive patients, patients with lower ESR levels, patients with lower or higher DAS28 score and patients with a lower functional class. These findings suggested that the functional SNP BLK rs2248932 T/C variant allele was associated with RA development. However, our results were obtained from a moderate-sized sample, and therefore this is a preliminary conclusion. Validation in a larger study from a more diverse ethnic population is needed to confirm these findings.     

No evidence for an association between the -871 T/C promoter polymorphism in the B-cell-activating factor gene and primary Sjögren's syndrome

Polyclonal B cell activation might be related to pathogenic over-expression of B-cell-activating factor (BAFF) in primary Sj?gren's syndrome (pSS) and other autoimmune diseases. We therefore investigated whether BAFF over-expression in pSS could be a primary, genetically determined event that leads to the disease. The complete BAFF gene was sequenced in Caucasian pSS patients and control individuals. The only single nucleotide polymorphism frequently observed, namely -871 T/C in the promoter region, was then genotyped in 162 French patients with pSS and 90 French control individuals. No significant differences in allele (T allele frequency: 49.7% in patients with pSS versus 50% in controls; P = 0.94) and genotype frequencies of BAFF polymorphism were detected between pSS patients and control individuals. BAFF gene polymorphism was not associated with a specific pattern of antibody secretion either. T allele carriers had significantly increased BAFF protein serum levels (mean values of 8.6 and 5.7 ng/ml in patients with TT and TC genotypes, respectively, versus 3.3 ng/ml in patients with CC genotype; P = 0.01), although no correlation was observed between BAFF polymorphism and mRNA level. In conclusion, BAFF gene polymorphism is neither involved in genetic predisposition to pSS nor associated with a specific pattern of antibody production.     

Association between melanopsin gene polymorphism (I394T) and pupillary light reflex is dependent on light wavelength

Background

Our aim was to determine the association between melanopsin gene polymorphism and pupillary light reflex under diverse photic conditions, including different intensities and wavelengths.

Methods

A total of 195 visually corrected subjects volunteered for investigation of the melanopsin gene of single nucleotide polymorphism (SNP) of rs1079610 (I394T). The genotype groups were TT (n = 126), TC (n = 55), and CC (n = 8), and 75 of the subjects, including subjects with TT (n = 34), TC (n = 33), and CC (n = 8) participated in our experiment. Three monochromatic lights with peak wavelengths of 465 nm (blue), 536 nm (green), and 632 nm (red) were prepared, and each light was projected to the subjects with five intensities, 12, 13, 14, 14.5 and 15 log photons/(cm² s), for one minute. The pupil size of the left eye was measured under each light condition after a 1-minute adaptation.

Results

The pupils of the TC + CC genotypes (n = 38) were significantly smaller than those of the TT genotype (n = 31) under a blue (463 nm) light condition with 15 log photons/(cm² s) (P < 0.05). In contrast, there were no significant differences under green (536 nm) and red (632 nm) light conditions. Conversely, relative pupil constrictions of the TC + CC genotypes were greater than those of the TT genotype under both blue and green conditions with high intensities (14.5 and 15 log photons/(cm² s)). In contrast, there were no significant differences between genotype groups in pupil size and relative pupilloconstriction under the red light conditions.

Conclusions

Our findings suggest that the melanopsin gene polymorphism (I394T) functionally interacts with pupillary light reflex, depending on light intensity and, particularly, wavelength, and that under a light condition fulfilling both high intensity and short wavelength, the pupillary light response of subjects with the C allele (TC + CC) is more sensitive to light than that of subjects with the TT genotype.     

No evidence for an association between the -871 T/C promoter polymorphism in the B-cell-activating factor gene and primary Sjögren's syndrome

Polyclonal B cell activation might be related to pathogenic over-expression of B-cell-activating factor (BAFF) in primary Sjögren's syndrome (pSS) and other autoimmune diseases. We therefore investigated whether BAFF over-expression in pSS could be a primary, genetically determined event that leads to the disease. The complete BAFF gene was sequenced in Caucasian pSS patients and control individuals. The only single nucleotide polymorphism frequently observed, namely -871 T/C in the promoter region, was then genotyped in 162 French patients with pSS and 90 French control individuals. No significant differences in allele (T allele frequency: 49.7% in patients with pSS versus 50% in controls; P = 0.94) and genotype frequencies of BAFF polymorphism were detected between pSS patients and control individuals. BAFF gene polymorphism was not associated with a specific pattern of antibody secretion either. T allele carriers had significantly increased BAFF protein serum levels (mean values of 8.6 and 5.7 ng/ml in patients with TT and TC genotypes, respectively, versus 3.3 ng/ml in patients with CC genotype; P = 0.01), although no correlation was observed between BAFF polymorphism and mRNA level. In conclusion, BAFF gene polymorphism is neither involved in genetic predisposition to pSS nor associated with a specific pattern of antibody production.     

Effect of leptin gene polymorphism on the breeding value of milk production traits in Iranian Holstein

New molecular techniques focused on genome analysis, open new possibilities for more accurate evaluation of economiclly important traits in farm animals. Milk production traits are typical quantitative characteristics controlled by a number of genes. Mutations in their sequences may alter animal performance as well as their breeding values. In this study, we investigated the effect of Kpn2I restriction fragment length polymorphisms in the leptin gene, on bull breeding values for milk yield, fat, and protein yield, and their percentage. In order to test for an association between the leptin single-nucleotide polymorphism in exon 2 and milk productivity, we genotyped 134 Iranian Holstein bulls. Breeding values for milk-related traits (milk yield, fat, and protein yield and percentage) were estimated using the BLUP based on an animal model. The effect of the genotypes of Kpn2I polymorphism on the breeding values for milk-related traits was examined using least square methods. The T allele frequency was 0.425. Genotypes were distributed according to the Hardy-Weinberg equilibrium. Bulls with TT genotype had higher milk, fat and protein yield compared with TC and CC bulls (P < 0.05). Bulls with CC genotype had higher protein percentage compared with TT and TC bulls (P < 0.05). The association between leptin polymorphism with milk production traits suggests that this marker may be useful for selection based on molecular information.     

The association between proinflammatory cytokine polymorphisms and cerebral palsy in very preterm infants

Cerebral palsy (CP) is a nonprogressive motor disorder caused by white matter damage in the developing brain and is often accompanied with cognitive and sensory disabilities. The risk of CP is higher among infants born preterm than in more mature infants. Intrauterine infection/inflammation, activation of the cytokine network and elevated levels of proinflammatory cytokines in neonatal blood or in amniotic fluid to which the preterm infant is exposed, has been identified as the most common cause of preterm delivery, periventricular leukomalacia (PVL) and CP. The aim of our study was to evaluate the possible association of four TNFα promoter single nucleotide polymorphisms (SNPs) (-1031 T/C, -857 C/T, -308 G/A and -238 G/A), two IL1β SNPs (-511 C/T and +3954 C/T) and one IL6 (-174 C/G) polymorphism with susceptibility to CP in very preterm infants. Statistically significant association between TNFα -1031 T/C high expression genotypes (TC and CC) (OR, 2.339; p=0.016) as well as between TNFα -1031 C high expression allele (OR, 2.065; p=0.013) and risk of CP was observed. In addition, statistically significant association was found between TNFα TC, CC, GG, GG -1031/-857/-308/-238 genotypes combination (OR, 3.286; p=0.034) and risk of CP. Statistically significant association between IL1β TT, CC -511/+3954 genotypes combination and risk of CP (OR, 4.000; p=0.027) was also found. In CP patients with cystic PVL (cPVL) statistically significant association was found between TNFα -1031 T/C high expression genotypes (TC and CC) (OR, 2.361; p=0.038), IL1β -511 C/T high expression genotype TT (OR, 3.215; p=0.030) as well as IL1β -511 T high expression allele (OR, 1.956; p=0.019) and risk of CP. Statistically significant association was also found in patients with cPVL between TNFα TC, CC, GG, GG -1031/-857/-308/-238 genotypes combination (OR, 4.107; p=0.024), as well as IL1β TT, CC -511/+3954 genotypes combination (OR, 7.333; p=0.005) and risk of CP. Our results suggest the role of TNFα and IL1β polymorphisms which have previously been associated with higher circulating levels of these cytokines in genetic susceptibility to white matter damage and consequently CP in very preterm infants.     

Association between polymorphisms in the SLC27A1 gene and milk production traits in Chinese Holstein cattle

We assessed SLC27A1, a candidate gene for milk production traits in Chinese Holstein cattle. DNA was extracted from the blood of 48 top Chinese Holstein Cattle selected according to phenotypic character and mixed into DNA pool for SNP detection. We tested blood samples of these cattle for SNPs in exon 3 and the 3'-flanking region of the SLC27A1 gene by using polymerase chain reaction-single-stranded conformation polymorphism (PCR-SSCP) and DNA sequencing. We found 2 polymorphic sites: 112T>C, a synonymous mutation, in exon 3 (SNP(1)), and 64G>A in the 3'-UTR (SNP(2)). We also determined the genotypes of 330 Chinese Holstein cattle by using PCR-restriction fragment length polymorphism (RFLP). We found 3 genotypes each at SNP(1) (TT, TC, and CC) and SNP(2) (GG, GA, and AA). The association among the different genotypes at these 2 sites and milk production traits was analyzed using a least-squares procedure. The results showed that cows with genotype CC had higher milk yields than those with genotype TC (0.01 < p < 0.05). No significant difference was detected among the 3 SNP(2) genotypes in terms of milk production traits. Our results provide evidence that the C allele have potential effects on milk yield trait.     

The Relationship between Gene Polymorphism and CRP Level in a Chinese Han Population

We investigated the relationships among the +1444C/T polymorphism in the C-reactive protein (CRP) gene and the concentration of CRP and the risk of coronary heart disease. Using polymerase chain reaction-restriction fragment length polymorphism, we analyzed the frequency distribution of genotypes and alleles of the +1444C/T polymorphism in samples from 128 patients with coronary heart disease (coronary stenosis more than 50%) and 119 unrelated normal individuals. The plasma levels of CRP and lipids in the subjects were also measured. The frequencies of the genotypes were CC 89.1%, CT 10.9%, and TT 0% in patients and CC 89.9%, CT 10.1%, and TT 0% in controls. The frequency of allele C was 94.5% in patients and 95.0% in controls, and allele T was 5.5% in patients and 5.1% in controls. The distribution of genotypes and alleles in the Chinese Han population was significantly different from that of the Caucasian population. There were no significant differences between frequencies of genotype and allele of controls and those of patients (P>0.05), but in controls the concentrations of CRP in the CC genotype subgroup were significantly higher than those in the CT genotype subgroup (P<0.05). This suggests that the +1444C/T variant in the CRP gene influences the basal CRP level in normal people. These findings imply that there may eventually be a need to establish genotype-specific risk thresholds of the CRP level.     

IFNL4 and IFNL3 Associated Polymorphisms Strongly Influence the Spontaneous IFN-Alpha Receptor-1 Expression in HCV-Infected Patients

Single-nucleotide polymorphism in IFNL3 gene (rs12979860) predicts spontaneous and therapy-induced HCV clearance. In a previous study from our group PBMC from patients with favourable rs12979860 genotype showed higher levels of IFNAR-1 mRNA. Recently, a dinucleotide polymorphism, ss469415590 (TT or ΔG), has been discovered in the region upstream IFNL3 gene, which is in high linkage disequilibrium with rs12979860. ss469415590[ΔG] is a frameshift variant that creates a novel gene, designed IFNL4, encoding the interferon-lambda 4 protein (IFNL4). The aim of the present study was to extend the analysis of IFNAR-1 mRNA levels to the ss469415590 variants. Our results highlight that the difference of IFNAR-1 mRNA levels between favourable and unfavourable genotype combinations, at both rs12979860 and ss469415590 loci, is stronger than that observed for single polymorphisms at each locus. These findings suggest may represent the biological basis for the observed association between IFNL3 CC and IFNL4 TT/TT genotypes and favourable outcome of either natural HCV infection (clearance vs chronic evolution) or IFN-based therapy.     

Association of interleukin 1beta gene (+3953) polymorphism and severity of endometriosis in Turkish women

Endometriosis is regarded as a complex trait, in which genetic and environmental factors contribute to the disease phenotype. We investigated whether the interleukin (IL) 1beta (+3953) polymorphism is associated with the severity of endometriosis. Diagnosis of endometriosis was made on the basis of laparoscopic findings. Stage of endometriosis was determined according to the Revised American Fertility Society classification. 118 women were enrolled in the study. 78 women didnot have endometriosis, 6 women had stage I, 3 had stage II, 13 had stage III and 18 had stage IV endometriosis. Polymerase Chain Reaction (PCR), Restriction Fragment Length Polymorphism (RFLP), and agarose gel electrophoresis techniques were used to determine the IL 1beta (+3953) genotype. Frequencies of the IL-1beta (+3953) genotypes in the control group were: CC, 0.397; TT, 0.115; CT, 0.487. Frequencies of the IL-1beta (+3953) genotypes in cases were: CC, 0.375; TT, 0.225; CT, 0.400. We found a 2.22 fold increase in TT genotype in the endometriosis group. However, the difference was not statistically significant (P > 0.05). We also observed an increase in the frequency of IL-1beta (+3953) T allele in the endometriosis group. However, the difference was not statistically significant. We also investigated the association between IL-1beta (+3953) polymorphism and the severity of endometriosis. The frequencies of CC+CT genotypes in stage I, III and IV endometriosis patients were 83.3, 84/6 and 72.2%, respectively; and TT genotypes were 16.7, 15.4 and 27.8%, respectively. We observed a statistically insignificant increase in TT genotype in stage IV endometriosis (P > 0.05). We suggest that IL-1beta (+3953) polymorphism is not associated with endometriosis in Turkish women.