SEARCH · PubMed Health

Results for “Hinge Exons”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

159 records · Page 9Linked to original sources

PubMedDate not supplied

Identification of novel mutations and the three most common mutations in the human ATP7B gene of Korean patients with Wilson disease.

PURPOSE: Wilson disease, an autosomal recessive disorder of copper transport, is probably the most common inherited metabolic disorder in Korea. In Wilson disease, synthesis of a defective copper transporting enzyme leads to the accumulation of copper in the liver, brain, and kidney. The product of the Wilson disease gene is a copper transporting P-type ATPase (ATP7B). In this study, efforts were made to identify novel mutations and investigate the frequency of the common mutations in Korean patients with Wilson disease. METHODS: This study includes 37 patients from 33 unrelated Korean families with Wilson disease. Genomic DNA from peripheral leukocytes or skin fibroblasts and cDNA from liver tissue were polymerase chain reaction-amplified exon by exon and subsequently analyzed using heteroduplex or single-strand conformation polymorphism analysis. Specimens showing mobility shift on those studies were directly sequenced. RESULTS: Twelve different mutations in 33 Korean families with Wilson disease were identified: Arg778Leu (R778L), Asn1270Ser (N1270S), Ala874Val (A874V), 2303-2305delC, 2630-2656del, 2460-2462insC, Cys656Stop (C656X), Pro768His (P768H), Leu1083Phe (L1083F), Ala1168Ser (A1168S), Leu1255Ile (L1255I), and Asp1267Ala (D1267A). Among these, six mutations (2630-2656del, 2460-2462insC, C656X, P768H, A1168S, and L1255I) are novel. The R778L mutation is known to be highly prevalent in Asian patients. The allele frequency of R778L in Korean patients with Wilson disease was 37.9%, which was significantly higher than those of Japanese and Taiwanese patients. The N1270S mutation, originally described in an Italian patient, was the next most common mutation in Korean patients, with an allele frequency of 12.1%, which was presumed to disrupt the ATP hinge domain of the ATP7B protein. The A874V mutation was the third most common mutation with an allele frequency of 9.4%, which was presumed to disrupt the Td domain of the ATP7B protein. CONCLUSION: The R778L, N1270S, and A874V mutations are three major mutations representing approximately 60% of mutated alleles, although Korean patients with Wilson disease are genetically heterogeneous.

Adenosine Triphosphatases↗

PubMed1996

The gene responsible for adrenal hypoplasia congenita, DAX-1, encodes a nuclear hormone receptor that defines a new class within the superfamily.

X-linked adrenal hypoplasia congenita (AHC) is an inherited disorder of the development of the adrenal cortex. The gene responsible for this genetic disorder has been identified using positional cloning methods and has been named DAX-1 based on its localization within the dosage-sensitive sex reversal (DSS) locus and the AHC locus on the X chromosome. The DAX-1 gene consists of two exons separated by a 3.4 kb intron. Analysis of DNA from patients with deletions in the AHC critical region in the X chromosome provided strong indication for the involvement of the DAX-1 gene in X-linked AHC. A number of intragenic mutations within the DAX-1 gene have also been identified in patients with isolated AHC. The DAX-1 gene product belongs to the nuclear hormone receptor superfamily based on the presence of an entire ligand binding domain present in the carboxy-terminal region of the receptor. However, DAX-1 has a domain structure which is very unusual with respect to other nuclear hormone receptor superfamily members. The amino-terminal portion of DAX-1 contains a novel domain consisting of 3.5 repeats of a 65-67 amino acid motif that contains two putative zinc finger structures in place of the more usual amino-terminal domain, DNA binding domain, and hinge region of the typical nuclear hormone receptors. It has been proposed that the amino-terminal portion of the DAX-1 protein is the DNA binding domain. The expression pattern of DAX-1 suggests that it may play a role in the regulation of steroidogenesis. Not only is DAX-1 expressed in the adrenal glands, but it is also expressed in the ovaries and testes. Most recently, we demonstrated that DAX-1 is also expressed in the hypothalamus and pituitary gland. The expression of DAX-1 in the neuroendocrine system suggests that interruption of the expression in these tissues may be the cause of the hypogonadotropic hypogonadism (HH) that is frequently associated with AHC. Interestingly, hybridization of a human DAX-1 cDNA probe with genomic DNA from various species indicated that a DAX-1 homologue may exist in yeast. Thus, DAX-1 or a DAX-1-like transcription factor may be the most primitive member of the nuclear hormone receptor superfamily. Although the molecular mechanism of action of DAX-1 is not yet characterized, its importance for the development and physiology of the adrenal gland and gonads is indicated by its involvement in AHC and HH. Analysis of the functions of DAX-1 along with its regulation of expression will not only provide information concerning the actions of this new member of the nuclear hormone receptor superfamily, but will also yield insight into the pathogenesis of AHC and HH and may allow for the development of gene therapy protocols for the treatment of these diseases.

Adrenal Insufficiency↗

PubMed1989

vav, a novel human oncogene derived from a locus ubiquitously expressed in hematopoietic cells.

A novel human oncogene, designated vav, was generated by a genetic rearrangement during gene transfer assays. The vav oncogene directs the synthesis of a 3.0 kb mRNA from which we isolated a 2.8 kb-long complementary DNA copy. Nucleotide sequence analysis of this vav oncogene cDNA clone revealed that its 5' 167 bp were derived from pSV2neo DNA cotransfected as a selectable marker during gene transfer. The remaining 2597 bp were unrelated to genes included in current data banks, indicating that the vav oncogene is likely to be derived from a novel human locus. The vav oncogene cDNA clone encompasses a 2391 bp long open reading frame (ORF) capable of directing the synthesis of a 797 amino acid long polypeptide. The predicted vav oncogene protein sequence exhibits several motifs reminiscent of transcriptional factors. They include a highly acidic amino-terminal region separated from two putative nuclear localization signals by a proline-rich sequence, presumably a hinge region. In addition, we identified two zinc-finger-like domains, one of which conforms to the canonical pattern Cys-X2-Cys-X13-Cys-X2-Cys previously found to confer trans-activating activity to the adenovirus E1A protein. Transcription of its normal allele, the vav proto-oncogene, has been exclusively observed in cells of hematopoietic origin, including those of erythroid, lymphoid and myeloid lineages. These findings raise the possibility that this novel locus might play an important role in hematopoiesis.

Amino Acid Sequence↗

PubMed2002

RAP80, a novel nuclear protein that interacts with the retinoid-related testis-associated receptor.

In this study, we describe the characterization of a novel nuclear protein, referred to as RAP80. The RAP80 cDNA was cloned from a human testis cDNA library and encodes a 719-amino acid protein containing two potential CX(2)CX(11)HX(3)C-type zinc finger motifs at its carboxyl-terminal region. Analysis of its genomic structure revealed that the RAP80 gene covers more than 90 kb and consists of 15 exons and 14 introns. Fluorescence in situ hybridization mapped the RAP80 gene to human chromosome 5q35. RAP80 mRNA is expressed in many human tissues, but its expression is particularly high in testis. In situ hybridization showed that RAP80 is highly expressed in germ cells of mouse testis but is not differentially regulated during spermatogenesis. Confocal microscopy showed that RAP80 is localized to the nucleus, where it is distributed in a speckled pattern. Deletion analysis showed that a bipartite nuclear localization signal at the amino terminus is important in mediating nuclear transport of RAP80. Monohybrid analysis showed that RAP80 might function as an active repressor of transcription. Mammalian two-hybrid analysis demonstrated that RAP80 was able to interact with the retinoid-related testis-associated receptor (RTR), an orphan receptor that has been implicated in the control of embryonic development and spermatogenesis. Pull-down analysis showed that RAP80 and RTR physically interact in vitro. Deletion and point mutation analyses revealed that part of the hinge domain of RTR is required for this interaction. RAP80 is able to inhibit the interaction of RTR with the co-repressor N-CoR likely by competing with N-CoR for RTR binding. Our results suggest that RAP80 may be functioning as a modulator of RTR signaling.

Alternative Splicing↗

PubMed2006

Endothelial nitric oxide synthase G894T (Glu298Asp) polymorphism was predictive of glycemic status in a 5-year prospective study of Chinese subjects with impaired glucose tolerance.

Subjects with impaired glucose tolerance (IGT) have a high risk of developing type 2 diabetes mellitus (DM) and its related complications. However, both environmental and genetic factors may influence the progression or regression of hyperglycemia. Polymorphisms of the endothelial nitric oxide synthase (eNOS) gene have been associated with DM in cross-sectional studies, but their predictive values in glycemic progression are not known. We examined the relationship of the eNOS promoter -T786C (-T786C), intron 4 variable tandem repeat (in4a/b), and exon 7 G894T (G894T) polymorphisms, and their haplotypes, with the long-term glycemic outcome in a Chinese cohort with IGT. Two hundred fifty-six Chinese subjects with IGT at baseline participated in a 5-year follow-up study to assess their glycemic outcome. Each individual was genotyped for the above-mentioned polymorphisms. At 5 years, 40.2% of the subjects had reverted to normal glucose tolerance; 39.9% remained in IGT/impaired fasting glucose and 19.9% had developed DM. A significant gene effect of exon 7 G894T polymorphism on glycemic status at 5 years was demonstrated, with carriers of T(894) being more likely to have persistent hyperglycemia compared with GG subjects (P = .003). On stepwise logistic regression analysis, the presence of the T allele remained a significant risk factor for persistent hyperglycemia (odds ratio, 2.72; 95% confidence interval, 1.36-5.99; T+ vs GG; P = .013), together with male sex, high body mass index, and high 2-hour glucose at baseline. No significant effect of -T786C or in4a/b polymorphism on fifth-year glycemic status was observed. The eNOS G894T polymorphism appears to be predictive of persistent hyperglycemia in Chinese subjects with IGT.

Adult↗

PubMed2002

Generation of multiple farnesoid-X-receptor isoforms through the use of alternative promoters.

Bile acid biosynthesis is regulated by both feed-forward and feedback mechanisms involving a cascade of nuclear hormone receptors. Feed-forward regulation of the rate limiting enzyme in bile acid biosynthesis is provided by oxysterols through liver-X-receptor alpha (NR1H3), while feedback regulation is provided by bile acids through farnesoid-X-receptor (FXR) (NR1H4). The Syrian golden hamster provides a useful model for studying lipid metabolism. The hamster metabolizes and transports dietary cholesterol in a similar manner to humans, with the resulting lipid profile being more similar to the human profile than that of other rodent models. Cloning of Fxr from Syrian golden hamster revealed four hamster Fxr splice variants that altered the N-terminal activation domain or the hinge region between the DNA and ligand binding domains. Human genomic sequence and data from hamster Fxr were used to identify and clone a novel human FXR isoform resulting from the use of an alternative promoter. RNA expression analysis indicates that the two human FXR isoforms are differentially expressed in developmental and tissue-specific patterns and are likely to provide a mechanism for cell-specific FXR-dependent transcriptional activity.

Alternative Splicing↗

PubMed2001

Origin of bovine IgM structural variants.

The structure of IgM determined from two cDNAs isolated from a Holstein (BLV7G1) and an Angus x Hereford cross-bred (B5D8) cow reveals high sequence similarity both at nucleotide (98.7%) and amino acid (97.9%) level and is closest to sheep (89.4%). Three bovine IgM allotypes, designated as IgMa, IgMb and IgMc, are classified based on nucleotide substitutions in all the Cmu exons resulting in amino acid replacements. Further, insertion of three in-frame codons at Cmu1 and Cmu2 junction of B5D8 IgM from the intervening intron, via cleavage of pre-mRNA at an alternate cryptic 5' splice donor site, leads to generation of additional bovine IgM variants. The C1q-binding site, involved in classical complement pathway, is identified in bovine IgM where ten amino acids are conserved across species. Interestingly, bovine IgM has the lowest number of proline residues (5) in the Cmu2 domain in comparison to other species (7-9) and this is likely to impose structural constraints on mobility of Fab arms of the bovine IgM during antigen recognition. The rigidity in the bovine IgM Cmu2 domain may, however, facilitate exposure of C1q-binding site subsequent to antigen binding and enhance its complement fixing ability. The restricted mobility of bovine IgM Fab arms may possibly favor generation of an antigen-combining site requiring an unusually long third complementarity determining region of the heavy chain (CDR3H), apart from antigen selection of variable domains. This is consistent with the fact that an exceptionally long CDR3H has not been observed in bovine IgG which bears a long and more flexible hinge region. Additional hydrophilic threonine and serine residues in the Cmu2 domain of bovine IgM, as compared to other species, however, enhance its ability to extend into the solvent. Finally, restricted fragment length polymorphism analysis of genomic DNA from four cattle breeds reveals the presence of; at least, four allelic variants of bovine Cmu gene.

Amino Acid Sequence↗

PubMed1995

Isolation and characterization of the rat gene for carbamoylphosphate synthetase I.

Carbamoylphosphate synthetase I (CbmPS) is first expressed in rat hepatocytes shortly before birth. After birth, expression of CbmPS gradually becomes confined to the hepatocytes surrounding the portal veins. To obtain insight into the spatiotemporal regulation of its expression, the rat CbmPS gene was isolated and characterized. The gene is 110 kb in length and contains 38 exons. The basal promoter comprises the first 161 nucleotides upstream of the transcription-initiation site. Determination of the state of methylation of the 5' portion of the gene identified a CCGG sequence at -6.3 kb that is selectively demethylated in adult tissues which express CbmPS. This site remains methylated before birth, however, despite recruitment of all hepatocytes for CbmPS synthesis, indicating that its demethylation is a consequence of rather than a condition for expression of CbmPS. Transient expression assays revealed that the region surrounding the CCGG site at 6.3 kb functions as an enhancer. In FTO-2B hepatoma cells and Rat-1 fibroblasts, this enhancer is constitutively active when tested in front of the basal viral thymidine kinase promoter. When tested in front of the basal CbmPS promoter in hepatoma cells, however, the activity of this enhancer is dependent on the presence of glucocorticoids. In Rat-1 fibroblasts, the presence of both glucocorticoids and cyclic AMP is required for full activity, suggesting that the hepatocyte-specific expression of CbmPS is related to tissue-specific differences in the sensitivity to cyclic AMP. Matrix-attachment regions (MAR) are present upstream and downstream of the CbmPS gene. The downstream MAR defines the 3' boundary of the gene. The upstream MAR is located midway between the basal promoter and the enhancer, and may function as a hinge point to facilitate the positioning of the enhancer in the vicinity of the basal promoter.

Animals↗

PubMed2004

Associations between IL12B polymorphisms and tuberculosis in the Hong Kong Chinese population.

BACKGROUND: Interleukin (IL)-12 plays a vital role in regulating cell-mediated immunity against tuberculosis (TB). METHODS: To test whether IL12B genetic polymorphisms might contribute to human TB susceptibility, we examined the genotype frequencies of 5 IL12B polymorphisms (at promoter, intron 2, intron 4, exon 5, and 3' untranslated region [UTR]) in 516 patients with TB and 514 healthy control subjects from the Hong Kong Chinese population. RESULTS: Individuals homozygous for the IL12B intron 2-repeat marker (ATT)8 had a 2.1-fold increased risk of developing TB (P < .001) (odds ratio, 2.14 [95% confidence interval, 1.45-3.19]). Estimation of the frequencies of multiple-locus haplotypes composed of IL12B promoter, intron 2, intron 4, and 3' UTR alleles revealed potential risk haplotypes (designated "A" and "K") and protective haplotypes (designated "B") for TB. Furthermore, combining the genotype data of the 4 informative IL12B loci revealed a strong association between a specific genotype pattern, termed "diplotype I" (heterozygous A and K haplotypes), and TB. In contrast, diplotype II (homozygous BB haplotypes) appeared protective against TB. CONCLUSIONS: These findings support the association between IL12B intron 2 polymorphism and TB and between specific IL12B haplotypes and TB.

Asian People↗

PubMed1994

In vitro genetic analysis of the hinge region between helical elements P5-P4-P6 and P7-P3-P8 in the sunY group I self-splicing intron.

Modeling of the group I intron RNA suggests that its catalytic core is primarily composed of two extended structural elements (stacked helices P5-P4-P6 and P7-P3-P8) whose relative orientation is partially determined by base-triple interactions between paired regions P4 and P6, and single-stranded joining regions J6/7 and J3/4, respectively. In vitro genetic selection was used to isolate functional sequence variants of the proposed triple helical domain of the sunY intron. Comparative sequence analysis of the selected variants provided supporting evidence for the two previously established base-triples between P4 and J6/7 and provided the first experimental evidence for an interaction between P6(1) and J3/4(3). Sequence covariations also indicated that a simple relationship exists between the length of a single-stranded joining region, J3/4, and the identity of a particular base-pair, P4(1). Selected variants based on a core structure with an extra nucleotide inserted in J3/4 revealed two different responses to this structural perturbation: a base-triple interaction and an intrahelical bulged pyrimidine. Chemical modification analysis supported the existence of these alternative structures. The function of this region of the ribozyme can therefore be fulfilled by at least three different structures.

Animals↗

PubMed1992

Mapping the human liver/islet glucose transporter (GLUT2) gene within a genetic linkage map of chromosome 3q using a (CA)n dinucleotide repeat polymorphism and characterization of the polymorphism in three racial groups.

The human liver/islet glucose transporter (GLUT2), a candidate gene for diabetes, has been incorporated into a genetic linkage map for chromosome 3q using a (CA)n dinucleotide repeat polymorphism adjacent to the 3'-end of exon 4a. We have found a total of nine alleles ranging in length from 153 to 169 nucleotides in three racial groups and have determined the precise structure of the variable region for four of the alleles by DNA sequencing. Five alleles were found to be common to the American Black, Caucasian, and Pima Indian racial groups studied. One allele (169 bp) was unique to American Blacks, and another rare allele (153 bp) was found only in the Caucasian population studied. Observed heterozygosity of the polymorphism in the Caucasian (CEPH) reference pedigree collection is 60%, for American Blacks 71%, and for Pima Indians 53%. An independent study recently identified the same dinucleotide repeat and found six alleles in a Caucasian population (Froguel et al., 1991), a result that we confirm; however, our sequencing data indicate a different molecular structure for the polymorphism for some of the alleles. We have constructed a new genetic linkage map of chromosome 3q uniquely placing the GLUT2 gene between flanking markers D3S26 and D3S43. The genetic map consists of 23 loci (25 RFLPs and 2 (CA)n dinucleotide repeat markers) with 14 markers uniquely localized with odds of at least 1000:1. Three genes (FTHL4, TF, GLUT2) are integrated into the map, which spans a sex-average distance of 147.3 cM, 103.8 cM in males and 227.0 cM in females.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗

PubMed2005

Promoter hyper-methylation of calcium binding proteins S100A6 and S100A2 in human prostate cancer.

BACKGROUND: S100A6 and S100A2 are members of the S100 family of calcium binding proteins, which are down regulated in prostate cancer, however the molecular mechanism(s) underlying their loss of expression is unknown. METHODS: The promoter and exon 1 region of the S100A6 and S100A2 genes was sequenced in bisulfite modified DNA from non-malignant, benign prostatic hyperplasia (BPH), malignant and metastatic prostate tissues and in cell lines. Immunohistochemistry was performed to correlate S100A2 expression with methylation status. RESULTS: S100A6 methylation was absent or occurred at isolated sites in 14/14 cases of non-malignant epithelium and 5/5 cases of BPH tissues, whereas methylation was seen in 14/27 (52%) cases of prostatic cancer (P<0.0001), 2/2 cases of metastatic cancer and in the CWR22 prostatic cancer xenograft. Critical CpG sites within the S100A2 promoter were methylated in LNCaP, LNCaP-LN3, and CWR22 cells but not in Du145, PC3 or BPH45 cells. In tissues, S100A2 methylation was seen in 32/34 (94%) cases of adenocarcinoma and 5/5 cases of metastatic cancer. However, S100A2 methylation was also seen in 9/12 (75%) cases of non-malignant tissues and in 5/5 cases of BPH. Immunostaining, showed absent S100A2 expression all 41 cases of prostatic cancer, whereas staining was seen in the basal cells of non-malignant epithelium. CONCLUSIONS: Loss of S100A6 and S100A2 proteins is frequent in human prostatic cancer. A major mechanism underlying the loss of S100A6 expression appears to involve promoter hyper-methylation. However, mechanisms other than methylation of the known promoter are involved in silencing S100A2 in the prostate.

Adenocarcinoma↗

PubMed2002

Mutant luteinizing hormone receptors in a compound heterozygous patient with complete Leydig cell hypoplasia: abnormal processing causes signaling deficiency.

Over the past 5 yr several inactivating mutations in the LH receptor gene have been demonstrated to cause Leydig cell hypoplasia, a rare autosomal recessive form of male pseudohermaphroditism. Here, we report the identification of two new LH receptor mutations in a compound heterozygous case of complete Leydig hypoplasia and determine the cause of the signaling deficiency at a molecular level. On the paternal allele of the patient we identified in codon 343 a T to A transversion that changes a conserved cysteine in the hinge region of the receptor to serine (C343S); on the maternal allele a T to C transition causes another conserved cysteine at codon 543 in trans-membrane segment 5 to be altered to arginine (C543R). Both of these mutant receptors are completely devoid of hormone-induced cAMP reporter gene activation. Using Western blotting of expressed LH receptor protein with a hemagglutinin tag, we further show that despite complete absence of total and cell surface hormone binding, protein levels of both mutant LH receptors are only moderately affected. The expression and study of enhanced green fluorescent protein-tagged receptors confirmed this view and further indicated that initial translocation to the endoplasmic reticulum of these mutant receptors is normal. After that, however, translocation is halted or misrouted, and as a result, neither mutant ever reaches the cell surface, and they cannot bind hormone. This lack of processing is also indicated by reduced presence of an 80-kDa protein, the only N-linked glycosylated protein in the LH receptor protein profile. Thus, complete lack of signaling by the identified mutant LH receptors is caused by insufficient processing from the endoplasmic reticulum to the cell surface and results in complete Leydig cell hypoplasia in this patient.

Amino Acid Sequence↗

PubMed2007

Association of a TNAP haplotype with ankylosing spondylitis.

OBJECTIVE: To use a candidate gene approach to the identification of genetic markers that are significantly associated with ankylosing spondylitis (AS). METHODS: We genotyped 201 multiplex AS families with 1 exonic and 5 intronic single-nucleotide polymorphisms (SNPs) in TNAP, the gene that encodes tissue-nonspecific alkaline phosphatase, and performed family-based association analyses. RESULTS: In our cohort of 201 multiplex AS families, the TNAP haplotype rs3767155 (G)/rs3738099 (G)/rs1780329 (T) was significantly associated with AS (P = 0.032 by additive model). Haplotype-Based Association Testing (HBAT) analyses of AS families in which both men and women were affected showed that the same TNAP haplotype was significantly associated with AS (P = 0.002 by additive model). Using setafftrait code 1 0 0 in the HBAT program, testing specifically for affected men in AS families containing affected individuals of both sexes, this TNAP haplotype was also significantly associated with AS (P = 0.001 by additive model). The HBAT -p option (haplotype permutation test) was used to compute the "exact" P value via a Monte Carlo method for each haplotype (haplotype permutation test) and for the minimum observed P value among the haplotypes (whole marker permutation using the minimal P test), and both P values were statistically significant (2-sided P value for haplotype rs3767155 [G]/rs3738099 [G]/rs1780329 [T] = 0.00059, the smallest observed P value among all the individual haplotype scores = 0.003). Interestingly, this haplotype was not associated with AS in affected women from the same families. CONCLUSION: Our results indicate that the TNAP haplotype rs3767155 (G)/rs3738099 (G)/rs1780329 (T) is a novel genetic marker in men that is significantly associated with AS in multiplex families containing affected individuals of both sexes.

Adolescent↗

PubMed2005

ANKH variants associated with ankylosing spondylitis: gender differences.

The ank (progressive ankylosis) mutant mouse, which has a nonsense mutation in exon 12 of the inorganic pyrophosphate regulator gene (ank), exhibits aberrant joint ankylosis similar to human ankylosing spondylitis (AS). We previously performed family-based association analyses of 124 Caucasian AS families and showed that novel genetic markers in the 5' flanking region of ANKH (the human homolog of the murine ank gene) are modestly associated with AS. The objective of the present study was to conduct a more extensive evaluation of ANKH variants that are significantly associated with AS and to determine whether the association is gender specific. We genotyped 201 multiplex AS families with nine ANKH intragenetic and two flanking microsatellite markers, and performed family-based association analyses. We showed that ANKH variants located in two different regions of the ANKH gene were associated with AS. Results of haplotype analyses indicated that, after Bonferroni correction, the haplotype combination of rs26307 [C] and rs27356 [C] is significantly associated with AS in men (recessive/dominant model; P = 0.004), and the haplotype combination of rs28006 [C] and rs25957 [C] is significantly associated with AS in women (recessive/dominant model; P = 0.004). A test of interaction identified rs26307 (i.e. the region that was associated in men with AS) as showing a difference in the strength of the association by gender. The region associated with AS in women only showed significance in the test of interaction among the subset of families with affected individuals of both genders. These findings support the concept that ANKH plays a role in genetic susceptibility to AS and reveals a gender-genotype specificity in this interaction.

Adolescent↗