Diagnostic model generated by MRI-derived brain features in toddlers with autism spectrum disorder.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder mainly showed atypical social interaction, communication, and restricted, repetitive patterns of behavior, interests and activities. Now clinic diagnosis of ASD is mostly based on psychological evaluation, clinical observation and medical history. All these behavioral indexes could not avoid defects such as subjectivity and reporter-dependency. Therefore researchers devoted themselves to seek relatively stable biomarkers of ASD as supplementary diagnostic evidence. The goal of present study is to generate relatively stable predictive model based on anatomical brain features by using machine learning technique. Forty-six ASD children and thirty-nine development delay children aged from 18 to 37 months were evolved in. As a result, the predictive model generated by regional average cortical thickness of regions with top 20 highest importance of random forest classifier showed best diagnostic performance. And random forest was proved to be the optimal approach for neuroimaging data mining in small size set and thickness-based classification outperformed volume-based classification and surface area-based classification in ASD. The brain regions selected by the models might attract attention and the idea of considering biomarkers as a supplementary evidence of ASD diagnosis worth exploring. Autism Res 2017, 0: 000-000. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 620-630. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Autism spectrum disorder as early neurodevelopmental disorder: evidence from the brain imaging abnormalities in 2-3 years old toddlers.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that occurs within the first 3 years of life, which is marked by social skills and communication deficits along with stereotyped repetitive behavior. Although great efforts have been made to clarify the underlying neuroanatomical abnormalities and brain-behavior relationships in adolescents and adults with ASD, literature is still limited in information about the neurobiology of ASD in the early age of life. Brain images of 50 toddlers with ASD and 28 age, gender, and developmental quotient matched toddlers with developmental delay (DD) (control group) between ages 2 and 3 years were captured using combined magnetic resonance-based structural imaging and diffusion tensor imaging (DTI). Structural magnetic resonance imaging was applied to assess overall gray matter (GM) and white matter (WM) volumes, and regional alterations were assessed by voxel-based morphometry. DTI was used to investigate the white matter tract integrity. Compared with DD, significant increases were observed in ASD, primarily in global GM and WM volumes and in right superior temporal gyrus regional GM and WM volumes. Higher fractional anisotropy value was also observed in the corpus callosum, posterior cingulate cortex, and limbic lobes of ASD. The converging findings of structural and white matter abnormalities in ASD suggest that alterations in neural-anatomy of different brain regions may be involved in behavioral and cognitive deficits associated with ASD, especially in an early age of 2-3 years old toddlers.

Haplotype analysis of single nucleotide polymorphisms in anti-Müllerian hormone gene in Chinese PCOS women.

PURPOSE: Anti-Müllerian hormone (AMH) inhibits FSH-stimulated follicle growth and aromatase activity. The three fold higher serum AMH in PCOS patients may account for the increased number of small follicles and androgen level. We attempted to determine whether polymorphisms in AMH gene were associated with PCOS in Chinese han population. METHODS: A case-control study involving 475 PCOS patients and 512 normoovulatory women was conducted. Rs10407022 and rs8112524 were two tagging SNPs selected according to the HapMap database. Taqman assay was used for rs8112524 genotyping, and PCR-RFLP method for rs10407022. RESULTS: No significant difference was found in genotypic or allelic distributions of both of the two SNPs, rs10407022 and rs8112524, between PCOS women and controls. LH level and progesterone level were significantly higher in rs8112524 AA genotype in PCOS group (P = 0.012, 0.014 respectively). TA haplotype might enhance susceptibility to PCOS (P = 0.013, OR = 4.996, 95 % CI = 2.001-5.251), and GA haplotype might be protective (P = 0.000, OR = 0.117, 95 % CI = 0.049-0.417). CONCLUSIONS: Although individual TagSNPs in AMH gene do not affect susceptibility to PCOS, haplotypes of the two SNPs were associated with PCOS risk, as TA haplotype might enhance susceptibility to PCOS and GA inversely.

SNP rs2470152 in CYP19 is correlated to aromatase activity in Chinese polycystic ovary syndrome patients.

CYP19 encodes aromatase, a key enzyme essential for estrogen biosynthesis. Single nucleotide polymorphism (SNP) rs2470152 in CYP19 is associated with serum estradiol (E2) level and the E2/T (estradiol/testosterone) ratio. A case­control study including 661 individuals [364 polycystic ovary syndrome (PCOS) patients and 297 controls] was conducted to assess the association of SNP rs2470152 with PCOS. The subjects were genotyped using the polymerase chain reaction-restriction fragment length polymorphism method. Hormone levels were analyzed among various genotypes. The genotypic distributions of rs2470152 did not differ in PCOS patients when compared to the controls. However, differences in the E2/T ratio were detected, exhibiting a lower ratio in the heterozygous TC genotype in PCOS patients (p=0.01036) and controls (p=0.000). Testosterone levels also differed between the three genotypes of PCOS patients (p=0.00625), with a higher level in the TC genotype. Therefore, rs2470152 in CYP19 was not a major etiological factor for PCOS; however, the heterozygous TC genotype may inhibit aromatase activity, resulting in hyperandrogenism, particularly in PCOS patients.

Polymorphisms of the HSD17B6 and HSD17B5 genes in Chinese women with polycystic ovary syndrome.

OBJECTIVES: To investigate the polymorphisms of the 17ß-hydroxysteroid dehydrogenase type 5 and type 6 (HSD17B5 and HSD17B6) genes in Chinese women with polycystic ovary syndrome (PCOS). METHODS: Two hundred twenty-two PCOS patients and 283 controls were studied. Menarche age was recorded. Body mass indices (BMI) were calculated. Blood samples were obtained for single nucleotide polymorphism (SNP) analyses and hormone measurements. Genotyping of HSD17B6 and HSD17B5 in cases and controls was performed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: The SNP rs898611 of the HSD17B6 gene (TT, CT, CC) in women with PCOS (0.680, 0.270, 0.050, respectively) did not differ from those in controls (0.700, 0.258, 0.042, respectively), and the SNP rs3763676 of the HSD17B5 gene (AA, AG, GG) was rare in Chinese women. Total testosterone and other reproductive hormones, such as follicle-stimulating hormone (FSH), luteinizing hormone (LH), LH/FSH, and estradiol (E(2)), were also similar among the different genotypes of the HSD17B6 in the PCOS subjects and the controls, whereas BMI was different in the three genotypes of the HSD17B6 in PCOS subjects. CONCLUSIONS: Our data suggest that there is no association of HSD17B6 and HSD17B5 variants with the occurrence of PCOS in the Chinese population, but the polymorphism of SNP rs898611 is associated with BMI in PCOS patients.

Polymorphisms of TCF7L2 and HHEX genes in Chinese women with polycystic ovary syndrome.

PURPOSE: This study was to evaluate whether polymorphisms of TCF7L2 (rs7903146) and HHEX (rs1111875) genes responsible for insulin secretion are associated with the polycystic ovary syndrome (PCOS) in Chinese people. METHODS: 326 PCOS patients and 290 healthy individuals as controls were studied. Blood samples were obtained for DNA analyses and hormone measurements. Genotyping of the TCF7L2 (rs7903146) and HHEX (rs1111875) genes was carried out by the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: We did not find statistically significant differences in the distribution of the TCF7L2 rs7903146 and HHEX rs1111875 polymorphisms between the Chinese women with PCOS and the controls. Levels of hormones such as insulin, FSH, LH, LH/FSH, P, T and E2 were also similar between the different genotypes of the genes TCF7L2 and HHEX, respectively, which was confirmed within either the PCOS subjects or controls. CONCLUSIONS: There was no association of either of the two variants, rs7903146 of TCF7L2 and rs1111875 of HHEX, with the occurrence of PCOS in the Chinese population.

Association between CYP19 gene SNP rs2414096 polymorphism and polycystic ovary syndrome in Chinese women.

BACKGROUND: Several studies have reported the association of the SNP rs2414096 in the CYP19 gene with hyperandrogenism, which is one of the clinical manifestations of polycystic ovary syndrome (PCOS). These studies suggest that SNP rs2414096 may be involved in the etiopathogenisis of PCOS. To investigate whetherthe CYP19 gene SNP rs2414096 polymorphism is associated with the susceptibility to PCOS, we designed a case-controlled association study including 684 individuals. METHODS: A case-controlled association study including 684 individuals (386 PCOS patients and 298 controls) was performed to assess the association of SNP rs2414096 with PCOS. Genotyping of SNP rs2414096 was conducted by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method that was performed on genomic DNA isolated from blood leucocytes. Results were analyzed in respect to clinical test results. RESULTS: The genotypic distributions of rs2414096 (GG, AG, AA) in the CYP19 gene (GG, AG, AA) in women with PCOS (0.363, 0.474, 0.163, respectively) were significantly different from that in controls (0.242, 0.500, 0.258, respectively) (P = 0.001). E2/T was different between the AA and GG genotypes. Age at menarche (AAM) and FSH were also significantly different among the GG, AG, and AA genotypes in women with PCOS (P = 0.0391 and 0.0118, respectively). No differences were observed in body mass index (BMI) and other serum hormone concentrations among the three genotypes, either in the PCOS patients or controls. CONCLUSIONS: Our data suggest that SNP rs2414096 in the CYP19 gene is associated with susceptibility to PCOS.

Response of IGF and IL-6 to ovarian stimulation in PCOS and normal women.

The objective of the present study was to investigate the response patterns of insulin-like growth factors (IGFs) and interleukin-6 (IL-6) to ovarian stimulation within 24 h in patients with polycystic ovary syndrome (PCOS) in comparison with normally ovulating women. This controlled prospective clinical study involved 60 women who attended an infertility clinic. For the induction of the ovarian stimulation, fifty-two patients with PCOS and eight control cases were injected with human menopause gonadotropin (hMG) and human chorionic gonadotropin (hCG) during the early follicular phase of the natural or induced menstrual cycle. The blood was sampled before (0h) and 6, 12, 18, and 24 h after the stimulation. Serum levels of estradiol (E2), IGF-I, IGF-II and IL-6 were measured by radioimmunoassay. A significant decrease in serum IGF-II at 12 h was observed after a mixture of hMG and hCG was administered in patients with polycystic ovaries (PCO) including the typical PCOS group and the PCO + OA group (accumulated p < 0.05), while normal women presented a slight decrease (accumulated p < 0.1) 18h after the stimulation. Moreover, all the groups had similar serum levels of IL-6 and IGF-I at all time points. An increase in serum E2 occurred coincident with a decrease in IGF-II in all the groups except the ovarian hyperandrogenism patients (HA + OA group). Serum IGF-II levels, which appeared to be negatively correlated with elevated E2, statistically decreased in PCO patients early after hMG and hCG administration when monitored for 24 h, while no such changes were observed in IGF-I and IL-6.

Association between ACE gene I/D polymorphisms and hyperandrogenism in women with polycystic ovary syndrome (PCOS) and controls.

BACKGROUND: I/D polymorphisms of ACE are associated with the plasma ACE concentration. The ACE is associated with the angiogenesis of ovarian endothelium in vitro as well as steroidogenesis and follicular growth in cattle. Since ACE induces a high blood supply and hypersteroidogenesis in the ovary, it may be associated with polycystic ovary syndrome (PCOS) which exhibits hyperplasia, hypervascularity of the ovarian theca interna and stroma, as well as disorderd steroidogenesis. Therefore, we hypothesized that the ACE plays some roles in the human ovary. To investigate whether the ACE I/D polymorphisms are associated with the steroidogenesis disorder in PCOS and contribute to the susceptibility of PCOS in Chinese women, we designed a case-controlled association study in 582 individuals. METHODS: The ACE I/D polymorphisms were assessed in 582 reproductive-age women. Genotyping and frequency of ACE I/D polymorphisms were obtained by PCR amplification that was performed on genomic DNA isolated from blood leucocytes. Results were analyzed in respect to clinical test results. RESULTS: The frequencies of the D allele and the genotypic distributions (DD, ID and II) in the women with PCOS did not differ from those in controls (P = 0.458). However, there were significant differences in the concentrations of testosterone among three genotypes both in the PCOS patients and controls (P = 0.0045, P = 0.0052, respectively). Differences were also found between these groups with distinct genotypes: DD versus II and DI versus II in the PCOS patients as well as DD versus DI and DD versus II in the controls. There were significant differences in the ratio of LH/FSH among three genotypes in the patients (P = 0.01). However, there were no statistical differences in the BMI, AAM, E2 concentrations and other serum hormone concentrations among the three genotypes both in the PCOS patients and controls. CONCLUSION: The ACE I/D polymorphisms were not associated with the pathogenesis of PCOS. However, the polymorphisms were associated with the steroidogenesis in the ovary. The observation indicated that the ACE I/D polymorphisms were not the key etiological factor, which in stead may be associated with the aggravated clinical manifestations of PCOS.