Moderating Effects of Mindfulness in the Relation between Bullying Victimization and Sleep Disturbance in Chinese Children: Sex Differences.

Bullying victimization is associated with sleep disturbance. The present study aimed to investigate the impact of bullying victimization on sleep disturbance, and the moderating effect of mindfulness on this association, also exploring differences across sex. A sample of 420 Chinese children (Mage = 9.60, SD age = 1.11, 48.10% girls) in grade 3 to grade 6 were recruited to complete the revised Bully/Victim Questionnaire, the Chinese version of Pittsburg Sleep Quality Index, the Child and Adolescent Mindfulness Measure, as well as the Family Affluence Scale. Results showed that bullying victimization was positively associated with sleep disturbance (ß = 0.20, p < 0.001). And the effect of bullying victimization on sleep disturbance was moderated by mindfulness (ß = -0.16, p < 0.001), and the effect was invalid for children with high mindfulness (ß = 0.04, p > 0.05). Subgroup analyses indicated the buffering effect of mindfulness only existed among boys (ß = -0.19, p < 0.01) but not girls (ß = -0.11, p > 0.05), suggesting that mindfulness may buffer this association, mainly for boys.

Impaired CD8+ T cells in term pregnancy decidua with chronic hepatitis B virus infection.

PROBLEM: Hepatitis B virus (HBV) infection is more likely to develop a state of chronicity in early life, particularly mother-to-child transmission (MTCT) of HBV in the fetus during pregnancy. Till now, little is known about the impact of chronic HBV infection on the immune status of the maternal-fetus interface, and the immune profile of placental lymphocytes in MTCT of HBV is poorly understood. METHOD OF STUDY: Thirteen term pregnant women with chronic HBV infection (HBV-PW) and thirteen normal pregnant women as healthy control (HC-PW) were enrolled. The profile of placental immune cells and paired peripheral blood were analyzed by flow cytometry and immunohistochemistry. RESULTS: Compared with HC-PW, the frequency of CD8+ T cells from the term placenta of HBV-PW was significantly reduced. These cells showed decreased expression of activation molecules CD69 and HLA-DR; thus, decidual CD8+ T cells from HBV-PW demonstrated hypofunctional signature as evidenced by significantly reduced production of IFN-γ, as well as compromised ability of degranulation and proliferation. CONCLUSIONS: These findings supported that hypoactivated decidual CD8+ T cells might possess compromised ability in chronically HBV-infected term pregnant women. Our study provides robust evidence for the necessity and importance of antiviral intervention in HBV-PW to prevent MTCT of HBV.

CyPA interacts with SERPINH1 to promote extracellular matrix production and inhibit epithelial-mesenchymal transition of trophoblast via enhancing TGF-ß/Smad3 pathway in preeclampsia.

We previously reported that cyclophilin A (CyPA) production is upregulated in preeclampsia (PE). Moreover, CyPA is known to induce PE-like features in pregnant mice and impair trophoblast invasiveness. In this study, we further illustrated the role of CyPA in PE. RNA-seq analysis, RT-qPCR, immunohistochemical (IHC) staining, and western blotting of mouse placentae revealed that CyPA increased the levels of extracellular matrix (ECM) proteins, such as collagen I and fibronectin, and activated the TGF-ß/Smad3 signaling pathway. Additionally, CyPA inhibited the expression of genes involved in epithelial-mesenchymal transition (EMT) (e.g., E-cadherin, N-cadherin, and vimentin) in mouse placentae. We then constructed stable overexpressing and knock-down CyPA cell models (using HTR8/SVneo cells) to clarify the molecular mechanism. We found that CyPA regulated the levels of ECM-related proteins and the EMT process through the TGF-ß/Smad3 pathway. We also identified SERPINH1 as a putative CyPA-binding protein, using liquid chromatography-electrospray mass spectrometry (LC-MS)/MS. SERPINH1 was found to be upregulated in the placentae of PE. Silencing SERPINH1 expression reversed the upregulation of ECM proteins and inhibition of the EMT process induced by the overexpression of CyPA. These findings revealed the functions of CyPA in the impaired invasiveness of trophoblasts in PE and indicated that CyPA and SERPINH1 may represent promising targets for the treatment of PE.

Establishment and characterization of an ovarian yolk sac tumor patient-derived xenograft model.

OBJECTIVE: The lack of appropriate preclinical models of ovarian yolk sac tumor (OYST) is currently hindering the pursuit of new methods of treatment and investigation of the pathogenesis of the disease. We developed and characterized an OYST patient-derived xenograft (PDX) model in this study. METHODS: Tumor fragments from a patient with an OYST were implanted subcutaneously into BALB/c Nude mice. Engrafted xenografts were compared with the original tumor according to histology, immunohistochemistry, humanized identified, and drug efficacy testing with in vivo treatment programs. RESULTS: There was a high degree of histologic and immunohistochemical (IHC) resemblance between the established PDX model and its corresponding human tumors. Bleomycin, etoposide, and cisplatin (JEB) chemotherapy regimens were effective in clinical patients and were effective in the OYST PDX model; therefore, the effect of PDX intervention was consistent with clinical outcomes of OYSTs. CONCLUSION: We have successfully established an OYST PDX model. This OYST model preserves the basic molecular features of the primary human tumor, thereby providing a valuable method to preclinically evaluate new treatments and explore disease pathogenesis.

A Rare Case of Primary Signet-Ring Cell Cervical Carcinoma: Early Stage with Independent Bilateral Ovarian Metastases.

BACKGROUND: Primary signet-ring cell carcinoma of the uterine cervix (PSRCCC) is defined as a mucinous carcinoma. PSRCCC with independent bilateral ovarian metastases has not been previously reported in the literature. CASE PRESENTATION: Herein we describe a case of PSRCCC with ovarian involvement. The patient underwent a detailed complete physical examination, and surgery was then performed to resect all of the tumors. All tumors expressed human papillomavirus 18 no distant tumors were detected, and estrogen receptor and progesterone receptor testing were negative, suggesting that the cervix was the primary site. CONCLUSION: This is the first report of a case of PSRCCC metastasis to bilateral ovaries only. Conservative management of human papillomavirus-associated type endocervical adenocarcinomas with independent ovarian metastases should be considered.

Development and characterization of mammary intraductal (MIND) spontaneous metastasis models for triple-negative breast cancer in syngeneic mice.

Triple-negative breast cancer (TNBC) has a more aggressive phenotype and higher metastasis and recurrence rates than other breast cancer subtypes. TNBC currently lacks a transplantation model that is suitable for clinical simulations of the tumor microenvironment. Intraductal injection of tumor cells into the mammary duct could mimic the occurrence and development of breast cancer. Herein, we injected 4T1 cells into the mammary ducts of BALB/C mice to build a preclinical model of TNBC and optimized the related construction method to observe the occurrence and spontaneous metastasis of tumors. We compared the effects of different cell numbers on tumorigenesis rates, times to tumorigenesis, and metastases to determine the optimal number of cells for modelling. We demonstrated that 4T1-MIND model mice injected with 20,000 cells revealed a suitable tumor formation rate and time, thus indicating a potential treatment time window after distant metastasis. We also injected 20,000 cells directly into the breast fat pad or breast duct for parallel comparison. The results still showed that the 4T1-MIND model provides sufficient treatment time for lung metastases in mice and that it is a more reliable model for early tumor development. The 4T1-MIND model requires continuous improvement and optimization. A suitable and optimized model for translational research and studies on the microenvironment in TNBC should be developed.

Long noncoding RNA H19 promotes transforming growth factor-ß-induced epithelial-mesenchymal transition by acting as a competing endogenous RNA of miR-370-3p in ovarian cancer cells.

Ovarian cancer is a gynecological malignant tumor with a high mortality rate among women, owing to metastatic progression and recurrence. Acquisition of invasiveness is accompanied by the loss of epithelial features and a gain of a mesenchymal phenotype, a process known as epithelial-mesenchymal transition (EMT). Transforming growth factor-ß (TGF-ß) has been implicated in the regulation of EMT. In the present study, we aimed to investigate the role of long noncoding RNA H19 and microRNA-370 (miR-370-3p) in TGF-ß-induced EMT. Ovarian cancer cell lines SKOV-3 and OVCAR3 were incubated with different concentrations of TGF-ß, and the results showed that TGF-ß treatment upregulated H19 and downregulated miR-370-3p. In addition, an H19 knockdown or miR-370-3p overexpression suppressed TGF-ß-induced EMT, while H19 overexpression or a miR-370-3p knockdown promoted TGF-ß-induced EMT. Mechanistically, H19 could directly bind to miR-370-3p and effectively act as its competing endogenous RNA. Furthermore, we demonstrated that this activity of H19 was involved in its promotion of TGF-ß-induced EMT. Thus, our results may provide novel insights into the process of TGF-ß-induced EMT.

The expression characteristics of FAM71D and its association with sperm motility.

STUDY QUESTION: What are the features of FAM71D (Family with sequence similarity 71, member D) expression and is there an association between FAM71D expression and sperm motility? SUMMARY ANSWER: FAM71D, a novel protein exclusively expressed in the testis, is located in sperm flagella and is functionally involved in sperm motility. WHAT IS KNOWN ALREADY: Some testis-specific proteins have been reported as potential diagnostic biomarkers to evaluate the spermatogenesis process and sperm quality. We have identified a novel testis-specific protein, FAM71D, through microarray data analysis, yet little is known about its expression and function. STUDY DESIGN, SIZE, DURATION: FAM71D mRNA and protein expression was quantified during mouse testis development. Its localization in germ cells was detected by dual-labeled immunostaining in testis sections and sperm smears. The clinical significance was assessed by comparing FAM71D expression in spermatozoa from normozoospermic controls and asthenozoospermic patients. PARTICIPANTS/MATERIALS, SETTING, METHODS: Testes were dissected from C57BL/6 J male mice at postnatal ages of 1, 2, 3, 4, 6, 8 weeks and 6 months, and sperm was collected from cauda epididymides of adult mice by the swim-up method. Human spermatozoa were isolated from 100 human semen samples by density gradient Percoll centrifugation. RT-qPCR and western blot were performed to semi-quantify the expression of FAM71D in mouse testis, and in the ejaculated spermatozoa of normozoospermic controls and asthenozoospermic patients. Immunofluorescence staining was used to detect the localization of FAM71D. Co-immunoprecipitation assay was performed to evaluate the interaction between FAM71D and calmodulin. An antibody blocking assay was employed to assess the role of FAM71D in sperm motility. MAIN RESULTS AND THE ROLE OF CHANCE: Our results showed that FAM71D was exclusively expressed in the testis in an age-dependent manner. FAM71D expression exhibited dynamic change in the cytoplasm of spermatids during spermiogenesis and was finally retained in sperm flagella. FAM71D could interact with calmodulin. Use of anti-FAM71D antibody on sperm significantly decreased sperm motility. Expression level of FAM71D was markedly reduced in the ejaculated spermataozoa of asthenozoospermic patients (P < 0.05), and this was correlated with sperm progressive motility (r = 0.7435, P < 0.0001). LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: The sample size was limited and it is necessary to verify the correlation of FAM71D expression with sperm motility in larger cohorts. Furthermore, our results were descriptive and follow-up studies would be needed to elucidate the detailed role of FAM71D in sperm motility. WIDER IMPLICATIONS OF THE FINDINGS: This is the first systematic study to document the expression of endogenous FAM71D and a function for FAM71D in sperm motility. It provides new insights into our understanding of sperm motility regulation and causes of male infertility. STUDY FUNDING/COMPETING INTERESTS: This study was funded by the National Natural Science Foundation of China, Guangdong Natural Science Foundation and the Shenzhen Project of Science and Technology. The authors have no competing interests.

A nonsense mutation in Ccdc62 gene is responsible for spermiogenesis defects and male infertility in repro29/repro29 mice.

Phenotype-driven mutagenesis is an unbiased method to identify novel genes involved in spermatogenesis and other reproductive processes. Male repro29/repro29 mice generated by the Reproductive Genomics Program at the Jackson Laboratory were infertile with deformed sperm and poor motility. Using selected exonic capture and massively parallel sequencing technologies, we identified a nonsense mutation in the exon 6 of coiled-coil domain-containing 62 gene (Ccdc62), which results in a formation of a premature stop codon and a truncated protein. Among the tissues examined, CCDC62 was found to be expressed at the highest level in mouse testis by reverse transcriptase-PCR (RT-PCR) and Western blot analysis. With immunofluorescent staining, we demonstrated that CCDC62 was expressed in the cytoplasm and the developing acrosome in the spematids of mouse testis, and was specifically localized at the acrosome in mature sperm. The complementation analysis by mating repro29/+ mice with Ccdc62 -/- mice (generated by CRISPR-Cas9 strategy) further provided genetic proof that the infertility of repro29/repro29 mice was caused by Ccdc62 mutation. Finally, it was found that intracellular colocalization and interaction of CCDC62 and Golgi-associated PDZ and coiled-coil motif-containing protein may be important for acrosome formation. Taken together, this study identified a nonsense mutation in Ccdc62, which directly results in male infertility in repro29/repro29 mice.

Maternal HCV infection is associated with intrauterine fetal growth disturbance: A meta-analysis of observational studies.

Since the evidence regarding the association between maternal hepatitis C virus (HCV) infection and impaired intrauterine fetal growth had not been conclusive, the aim of the present study was to evaluate the risk of maternal HCV infection in association with intrauterine fetal growth restriction (IUGR) and/or low birth weight infants (LBW). We performed an extensive literature search of PubMed, MEDLINE, and EMBASE through December 1, 2015. The odds ratios (ORs) of HCV infection and IUGR/LBW were calculated and reported with 95% confidence intervals (95% CIs). Statistical analysis was performed using RevMen 5.3 and Stata 10.0. Seven studies involving 4,185,414 participants and 5094 HCV infection cases were included. Significant associations between HCV infection and IUGR (OR = 1.53, 95% CI: 1.40-1.68, fixed effect model) as well as LBW were observed (OR = 1.97, 95% CI: 1.43-2.71, random effect model). The results still indicated consistencies after adjusting for multiple risk factors which could affect fetal growth, including maternal age, parity, maternal smoking, alcohol abuse, drugs abuse, coinfected with HBV/HIV and preeclampsia. Our findings suggested that maternal HCV infection was significantly associated with an increased risk of impaired intrauterine fetal growth. In clinical practice, a closer monitoring of intrauterine fetal growth by a series of ultrasound might be necessary for HCV-infected pregnant population.

Deficiency of SPATA46, a Novel Nuclear Membrane Protein, Causes Subfertility in Male Mice.

Teratozoospermia is generally associated with clinical infertility. Despite numerous studies, the molecular mechanisms underlying male infertility are still poorly understood. In the present study, we demonstrated that deletion of Spata46, a gene encoding a novel protein of unknown function found in mouse testis, was responsible for male subfertility, and the cause of subfertility was characterized as abnormal sperm head shape and a failure of sperm-egg fusion. We also demonstrated that SPATA46 was expressed predominantly in condensed spermatids, with a highly specific localization restricted to the subacrosomal area; the protein is located at the nuclear membrane due to a transmembrane region in the N-terminus of the protein. At the subcellular level, SPATA46-deficient condensed spermatids displayed structural defects consisting of a discontinuous nuclear envelope and a cavity in the nucleus associated with an abnormal nuclear shape. Additionally, in vitro, we determined that the absence of SPATA46 led to accumulation of sperm around the perivitelline space of eggs, and the same phenomenon was also observed for natural sperm incubated with an anti-SPATA46 antibody, suggesting functional relevance of SPATA46 for sperm-egg fusion. Taken together, these results indicated that SPATA46 is a novel protein involved in reshaping of the sperm head and sperm-egg fusion.

Identification of NR0B1 as a novel androgen receptor co-repressor in mouse Sertoli cells.

Nuclear receptor subfamily 0 group B member 1 (Nr0b1) is an atypical member of the nuclear receptor family that is predominantly expressed in mouse Sertoli cells (SCs). Mutations of NR0B1 in humans cause adrenal failure and hypogonadotropic hypogonadism. The targeted mutagenesis of Nr0b1 in mice has revealed a primary gonadal defect characterized by the overexpression of aromatase and cellular obstruction of the seminiferous tubules and efferent ductules, leading to germ cell death and infertility. The transgenic expression of Nr0b1 under the control of the Müllerian-inhibiting substance promoter (MIS-Nr0b1), which is selectively expressed in SCs, improves fertility. Testicular androgen receptor (AR) was also expressed in SCs. Many genes are directly regulated by androgen and its AR, which are involved in spermatogenesis and male infertility. As the association between NR0B1 and AR remains unclear in mouse SCs, we decided to further explore the relationship between them. In the present study, we have identified NR0B1 as a novel AR co-repressor in mouse SCs. Using RT­qPCR and immunofluorescence, we determined that NR0B1 was mainly expressed in mouse SCs in an age-dependent manner from 2-8 weeks of age postnatally. The inhibition of the effects of AR on AR target genes by NR0B1, in an androgen­dependent manner, was further demonstrated by western blot analysis and RT-qPCR in TM4 cells, a mouse Sertoli cell line. Finally, in vitro luciferase and co-immunoprecipitation assays validated that NR0B1, as an AR co-repressor, significantly inhibited the transcriptional activation of its target genes. These results suggest that novel inhibitory mechanisms underlie the effects of NR0B1 in modulating androgen-dependent gene transcription in mouse SCs.

Identification and characteristics of the testes-specific gene, Ccdc38, in mice.

Distinguishing the testes-specific genes in different species may disclose key genes associated with testes-specific functions and provide sufficient information for the study and treatment of male infertility. A testes­specific gene, coiled-coil domain containing 38 (Ccdc38), was identified by screening UniGene libraries. Systematic bioinformatics analysis demonstrated that the CCDC38 protein was conserved in various mammalian species. It was determined that CCDC38 was exclusively expressed in testes and its expression increased from 2­8 weeks of age. Additional immunohistochemical analysis indicated that CCDC38 was mainly expressed in spermatogonia and spermatocytes. It is of note that, immunofluorescence and co-immunoprecipitation assays demonstrated that CCDC38 interacted with ubiquitinated histone H2A in mouse testes. Therefore, these results suggest that Ccdc38 is a testes-specific gene, which may be important for mouse spermatogenesis.

A Novel Missense Mutation in USP26 Gene Is Associated With Nonobstructive Azoospermia.

OBJECTIVE: The aim of this study was to evaluate whether ubiquitin-specific peptidase 26 (USP26) gene variations were associated with nonobstructive azoospermia (NOA). METHODS: Seven hundred and seventy-six patients diagnosed with NOA and 709 proven fertile men were included in this study. Genetic variations of infertility-related genes, including USP26, were identified by selected exonic sequencing. The effects of USP26 mutations on androgen receptor (AR) binding, ubiquitination, and transcriptional activity were detected by immunoprecipitation and luciferase assay in Hela and TM4 cells. RESULTS: Six novel missense mutations and 1 novel synonymous mutation of USP26 unique to the patients with NOA were identified. Of these missense mutations, USP26 R344W remarkably reduced the binding affinity and deubiquitinating activity of USP26 to AR, thus eliminated the inhibitory effect of USP26 on transcriptional activity of AR in Hela and TM4 cells. CONCLUSION: A novel USP26 variant p.R344W is associated with NOA probably through affecting AR function.

Protein Arginine Methyltransferase 6 Involved in Germ Cell Viability during Spermatogenesis and Down-Regulated by the Androgen Receptor.

Androgens and the androgen receptor (AR) are of great importance to spermatogenesis and male fertility. AR knockout (ARKO) mice display a complete insensitivity to androgens and male infertility; however, the exact molecular mechanism for this effect remains unclear. In this study, we found that the expression levels of Prmt6 mRNA and protein were significantly up-regulated in the testes of ARKO mice compared to wild type (WT) mice. PRMT6 was principally localized to the nucleus of spermatogonia and spermatocytes by immunofluorescence staining. Furthermore, luciferase assay data showed that AR together with testosterone treatment suppressed Prmt6 transcription via binding to the androgen-responsive element (ARE) of the Prmt6 promoter. Moreover, knockdown of Prmt6 suppressed germ cells migration and promoted apoptosis. In addition, both of these cellular activities could not be enhanced by testosterone treatment. Taken together, these data indicate that PRMT6, which was down-regulated by AR and influenced cell migration and apoptosis of germ cells, could play a potentially important role in spermatogenesis.

Androgen receptor binding to an androgen-responsive element in the promoter of the Srsf4 gene inhibits its expression in mouse Sertoli cells.

The serine/arginine-rich splicing actor 4 (SRSF4) is essential for pre-mRNA splicing and can influence alternative-splice-site choice. Little is known about the specific function of this gene in the reproductive system, although a recent study identified a SRSF4 polymorphism significantly associated with a decreased risk of non-obstructive azoospermia in Chinese men. We previously found that the expression of Srsf4 was up-regulated in the testes of Sertoli-cell-selective androgen receptor knockout (S-Ar(-/y)) mice compared to wild-type mice using digital gene expression analysis. In this study, we confirmed and extended the selective gene expression data: SRSF4 was mainly located in the nucleus of Sertoli cells, and Srsf4 expression in the Sertoli-cell-derived cell line TM4 is down-regulation by testosterone. Moreover, androgen receptor directly binds the androgen-responsive element of the Srsf4 promoter. Taken together, these results demonstrate that Srsf4 is a direct downstream target of the androgen receptor in mouse Sertoli cells.

FAM170B, a novel acrosomal protein involved in fertilization in mice.

The acrosome is a specialized organelle that covers the anterior region of the sperm nucleus, and plays an essential role in mammalian fertilization. Although acrosome biogenesis is an important aspect of spermiogenesis, the molecular mechanism that regulates this event remains unknown. In the present study, we identified a novel gene, Fam170b (family with sequence similarity 170, member B), exclusively expressed in mouse testes. Fam170b expression first started at postnatal week 3, and increased in an age-dependent manner until plateauing in adulthood. Immunofluorescence staining revealed its enrichment in round spermatids, and redistribution to a perinuclear spot adjacent to the Golgi and the acrosome of elongating spermatids and spermatozoa; this localization was shared between mouse and human spermatozoa. Anti-FAM170B antibody was remarkably found to inhibit murine in vitro fertilization, specifically blocking the acrosome reaction. We further determined that FAM170B interacts with GOPC (Golgi-associated PDZ and coiled-coil motif containing protein) during acrosome formation, as verified by immunofluorescence and co-immunoprecipitation assays. Thus, we document the expression and function for the endogenous acrosomal protein FAM170B during spermiogenesis and fertilization.

[Expression of a testis-specific gene 1700001022RIK in mice and its bioinformatic analysis].

OBJECTIVE: To identify the expression characteristics of the 1700001022RIK (RIKEN cDNA 1700001022) gene in mice and explore its function by bioinformatic analysis. METHODS: Using the expression profile of gene microarray, we detected the expression of a new testis-specific gene, 1700001022RIK, in mice. We analyzed its expression characteristics in the testis tissue and their changes in different developmental stages of the testis by RT-PCR, real-time RT-PCR, Western blot, and immunohistochemistry. We performed bioinformatic analysis using a bioinformatic software. RESULTS: The 1700001022RIK gene was specifically expressed in the mouse testis in an age-dependent manner, most highly in the adult mice. The 1700001022RIK protein was mainly expressed in the spermatogonia, spermatocytes, and round spermatids of the adult mice. Bioinformatic analysis showed that the 1700001022RIK protein amino acid sequence had a high similarity in human and mice, which indicated that this gene was highly conserved in mammals. CONCLUSION: 1700001022RIK is a testis-specific gene mainly expressed in the spermatogonia, spermatocytes, and round spermatids of seminiferous tubules, which might be involved in the regulation of spermatogenesis.

Genetic polymorphisms of pharmacogenomic VIP variants in the lhoba population of southwest China.

BACKGROUND: It is well-established that differences among ethnic groups in drug responses are primarily due to the genetic diversity of pharmacogenes. A number of genes or variants that play a crucial role in drug responses have been designated Very Important Pharmacogenes (VIP) by the PharmGKB database. Clarifying the polymorphic distribution of VIPs in different ethnic groups will aid in personalized medicine for specific populations. METHODS: We sequenced 85 VIP variants in the Lhoba population based on the PharmGKB database. The polymorphic distribution of the 85 VIP variants in 100 Lhoba subjects was determined and compared with that of 11 major HapMap populations, including ASW, CEU, CHB, CHD, GIH, JPT, LWK, MEX, MKK, TSI, and YRI. We used χ(2) tests to identify significantly different loci between these populations. We downloaded SNP allele frequencies from the ALlele FREquency Database to observe the global genetic variation distribution for these specific loci. And then we used Structure software to perform the genetic structure analysis of 12 populations. RESULTS: Based on comparisons of selected available loci, we found that 23, 28, 16, 10, 20, 16, 24, 19, 22, 21 and 36 of the selected VIP variant genotype frequencies in the Lhoba population differed from those of the ASW, CEU, CHB, CHD, GIH, JPT, LWK, MEX, MKK, TSI, and YRI populations, respectively. In addition, Pairwise FST values and clustering analyses also showed the VIP variants in Lhoba exhibited a close genetic affinity with CHD, CHB and JPT populations. CONCLUSION: Our results complement pharmacogenomic data on the Lhoba ethnic group and may be helpful in the diagnosis of certain diseases in minorities.