Differences in Minority Stress Experiences, Mental Health, and Relationship Quality Outcomes Among Bisexual, Pansexual, and Queer Women.

The majority of sexual minority women in the United States today identify as bi+. Recent research suggests that "non-traditional" bi+ labels such as pansexual and queer are being adopted more frequently than ever before, making it increasingly important to evaluate whether these women have unique needs. In the current study, we explored differences in minority stress experiences, mental health, and relationship quality outcomes by sexual identity label among women who identify with the most common bi+ labels: bisexual, pansexual, and queer. Participants were 285 bi+ cisgender women in romantic relationships. They completed online measures of minority stress (antibisexual experiences, identity concealment, disconnection from the sexual and gender minority (SGM) community, and internalized stigma), mental health (depression and anxiety), and relationship quality (satisfaction and commitment). Overall, participants reported similar experiences of minority stress and few differences in their mental health outcomes. However, there were differences in antibisexual experiences by sexual identity label, such that pansexual women reported more frequent antibisexual experiences than bisexual and queer women. There were also differences in relationship quality by sexual identity label, such that bisexual women reported higher satisfaction than pansexual women and higher commitment than both pansexual and queer women. Findings suggest that pansexual and queer women may be facing their own unique challenges, even compared to bisexual women. Clinical prevention and intervention efforts can be tailored for these women to include strategies to cope with more frequent exposure to antibisexual experiences, as well as relationship education and skill-building to promote healthy romantic relationships.

Sexual Agreements Among Young Sexual and Gender Minorities Assigned Male at Birth: Associations with Relationship Quality and Break-Up.

Previous studies have shown that sexual non-monogamy is not associated with lower relationship satisfaction among adult male same-sex couples and may therefore be a viable alternative to monogamy. However, sexual minority men with non-monogamous agreements have reported lower commitment and trust in their relationships than those with monogamous agreements-potentially raising their risk of break-up. In this study, we investigated whether sexual agreements (monogamous, non-monogamous, or no sexual agreement) were associated with relationship quality and rates of break-up over 1 year in a sample of 338 young sexual and gender minorities assigned male at birth (SGM-AMAB). Participants reported their sexual agreement and indices of relationship quality (satisfaction, trust, and commitment) at baseline, as well as their relationship status (intact or broken up) at 6- and 12-month follow-up. Results showed no significant differences by sexual agreement in concurrent trust, but participants with monogamous agreements reported higher satisfaction and commitment than those with non-monogamous agreements or no sexual agreement. Despite these significant differences in relationship quality, there were no significant differences in rates of break-up at 6- or 12-month follow-up across the sexual agreement types. However, having a monogamous agreement was indirectly associated with lower rates of break-up through relationship commitment. Although results were mixed, findings provide some preliminary support that young SGM-AMAB in relationships with monogamous agreements may have higher satisfaction and commitment at early relationship stages, and that monogamous agreements may be a protective factor against break-up over 1 year through the mechanism of relationship commitment.

Partner Assisted Smoking Cessation Treatment: A Randomized Clinical Trial.

Background: Partner Assisted Smoking Cessation Treatment (PACT) was designed to improve smoking abstinence rates by integrating evidence-based relationship education strategies to build effective couple support into standard cognitive behavioral smoking cessation treatment (CBT). Methods: This small randomized clinical trial examined the feasibility, acceptability, and efficacy of PACT versus CBT in improving couple support processes and smoking outcomes, focusing on effect sizes. Thirty-eight smokers and their nonsmoking partners were randomized to and completed either PACT or CBT. Both treatments included 8 weekly group sessions and nicotine replacement therapy. Results: Treatment credibility and satisfaction were high and comparable between conditions, though perceived helpfulness and treatment engagement were higher in PACT (ds = .48-.68). Compared to CBT, PACT showed no difference in effects on perceived partner support, small effects on observed social support behaviors (ds = .23 to .46), a medium effect on dyadic efficacy (d = .63), and a large effect on active listening (d = .85). Biochemically-verified smoking abstinence rates did not differ between conditions at 12-week follow-up (CBT: 27.3%, PACT: 37.5%). Conclusions: PACT may have stronger effects than standard CBT on treatment engagement and some couple support processes, but not abstinence. Program refinement and testing in larger samples are needed.

Romantic Involvement and Mental Health in Sexual and Gender Minority Emerging Adults Assigned Female at Birth.

We examined whether romantic relationship involvement, a well-established protective factor against mental health problems among heterosexual adults, is also protective for sexual and gender minority emerging adults assigned female at birth (SGM-AFAB), a group at high risk for mental health issues. Using cross-sectional data from a community sample of 222 SGM-AFAB ages 18-20 years, we assessed associations between current relationship involvement and five mental health variables: depressive symptoms, anxiety symptoms, alcohol use problems, cannabis use problems, and illicit drug use. There were no differences by romantic involvement in problematic cannabis use or other illicit drug use. Overall, participants in a relationship reported fewer depressive symptoms, fewer anxiety symptoms, and less problematic alcohol use than participants who were single. Some associations differed, however, by participant gender identity, sexual orientation identity, and partner gender. Specifically, relationship involvement was associated with fewer depressive and anxiety symptoms for cisgender female participants (n=154) but not for gender minority participants (n=68), and for lesbian participants (n=38) but not for bisexual/pansexual participants (n=134) or those with other sexual orientation identities (n=50). Participants romantically involved with a cisgender female partner (n=43) had fewer depressive and anxiety symptoms than single participants (n=100), those with a cisgender male partner (n=56), and those with a gender minority partner (n=23). Together, these findings suggest that romantic involvement may promote mental health for many, but not all, SGM young adults, highlighting the importance of attending to differences among SGM subgroups in research and efforts to reduce mental health and substance use disparities.

Weight change predicts college adjustment and depressive symptoms among first-year college students.

ObjectiveWeight change is common during the first year of college and may be related to different outcomes for men and women. This study examined the moderating effects of gender on the association between weight change and college adjustment and depressive symptoms. Participants: One-hundred and eighty-one 18-19-year-old college freshmen (56.9% female; 84.5% Caucasian). Methods: Students completed a one-time survey about demographics, weight, college adjustment, and depressive symptoms during their second semester of college. Results: Increased weight change was associated with fewer depressive symptoms for both men and women (p < .04). For men, increased weight change was associated with better overall college adjustment, more positivity about college, less negativity about college, and less homesickness (all p < .02). Conclusions: Universities could target men and women differently in regard to weight, college adjustment, and mental health to promote a positive college experience and optimal mental health.

Relationship, marriage, and parenthood aspirations among sexual and gender minority youth assigned female at birth.

This study examined aspirations for future long-term committed relationships, marriage, and parenthood in a sample of 392 racially diverse sexual and gender minority (SGM) youth assigned female at birth (AFAB) aged 16-20. Differences by gender identity, sexual identity, and race/ethnicity were assessed, as were associations with contextual variables including minority stressors, SGM community involvement, perceived partner availability, and relationship experiences. Results showed that the majority of SGM-AFAB youth viewed long-term committed relationships as important and likely, whereas only about half of participants had high aspirations to get married and have children someday. Those who did view marriage and parenthood as important perceived that it is feasible for them to achieve these outcomes someday. These constructs did not differ by race/ethnicity. There were differences by gender identity and sexual identity, such that cisgender women reported higher aspirations for marriage and parenthood than did gender minorities, and those with binary sexual identities reported higher aspirations for marriage than did those with nonbinary sexual identities. Examination of the contextual variables revealed that relationship experience variables were the most consistently associated with aspirations for committed relationships, marriage, and parenthood. In contrast, victimization and perceived partner availability were not associated with any of the family formation aspirations. As SGM individuals are increasingly granted legal rights affecting their ability to marry and form families, research is needed to help inform efforts to promote their relationship health while considering that they may have unique aspirations for relationships, marriage, and parenthood compared to the general public. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Mental health outcomes among individuals with 46,XY disorders of sex development: A systematic review.

This review summarizes research on the mental health outcomes of genetic males with a disorder of sex development (46,XY DSD). Databases were systematically searched, yielding 19 studies included in this review. Results varied widely, with mental health outcomes ranging from very poor to similar to comparison groups. A small number of studies demonstrated that patients with hypospadias or complete androgen insensitivity syndrome reported better mental health than patients with other 46,XY (DSD) diagnoses. Future studies should include larger samples of patients within a similar developmental stage, display results separately by DSD diagnosis and gender identity, and consider the potential impact of medical/surgical events on their mental health.

Within-person associations between romantic involvement and mental health among sexual and gender minorities assigned female-at-birth.

Sexual and gender minorities assigned female at birth (SGM-AFAB) experience significant mental health disparities, making it important to identify protective factors against psychological and substance use problems in this population. We examined whether romantic relationship involvement, a well-established protective factor for mental health in heterosexual adults, is protective for SGM-AFAB young people. Using five waves of data from 488 racially diverse SGM-AFAB (ages 16-31 years at baseline), we assessed within-person associations between relationship involvement and depressive symptoms, anxiety symptoms, and problematic alcohol and cannabis use. We tested for differences in these associations by age; sexual, gender, and racial identity; relationship status; and partner gender, and whether romantic involvement buffers the negative effects of anti-SGM victimization. Multilevel models indicated that participants reported fewer depressive symptoms, alcohol use problems, and cannabis use problems when romantically involved than when single. Romantic involvement was associated with fewer anxiety symptoms for Latinx participants only. Associations did not differ by age and were generally consistent (with some exceptions) across sexual, gender, and racial identity. Effects on substance use were stronger for long-term commitments than dating relationships. Participants reported less depression and anxiety, but more alcohol or cannabis use, when romantically involved with cisgender women than with cisgender men or gender minority partners. Together, findings suggest that relationship involvement is broadly protective of mental health among SGM-AFAB, though it may not buffer the negative effects of SGM victimization. Efforts to reduce SGM-AFAB mental health disparities should consider including strategies to support healthy relationship involvement. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Development of a LC-MS/MS method for the quantification of toxic payload DM1 cleaved from BT1718 in a Phase I study.

Background: BT1718 is a novel bicyclic peptide anticancer drug targeting membrane type I matrix metalloproteinase to release its toxic payload DM1. A LC-MS/MS method was validated to quantify DM1 generated from BT1718 in a Phase I/IIa clinical trial. Materials & methods: Plasma samples underwent a reduction reaction to artificially cleave BT1718 into DM1 and its bicycle components. An alkylation step was carried out to stabilize the reaction products, and plasma proteins extracted using acetonitrile. LC-MS/MS analysis utilized a C18 column and Agilent 6460 triple quadrupole mass spectrometer (Agilent, Cheshire, UK). Results: The method was fully validated over a linear range of 200-50,000 ng/ml BT1718, with overall precision ≤10% and accuracy 89-102%. Conclusion: A novel method for quantifying DM1 yielded from BT1718 has been validated and is now being utilized clinically.

Plasma rich in growth factor gel as an autologous filler for facial volume restoration.

BACKGROUND: Skin aging is characterized by moderate to severe wrinkles, laxity, roughness, and volume loss as a result of cutaneous atrophy and connective tissue degradation. Plasma rich in growth factor gel (PRGF-gel) is a novel formulation obtained from the patient's own blood that has demonstrated optimal biomechanical and bioactive properties for soft tissue restoration. OBJECTIVES: Following a retrospective design, the clinical safety and efficacy of PRGF-gel for facial volume restoration and skin rejuvenation were evaluated. METHODS: Twenty women clinically diagnosed for aged skin symptoms were treated with PRGF-gel. Participants received an individualized regimen depending on their therapeutic needs. At the end of the follow-up periods, clinical performance analysis was evaluated by standardized macrophotographs along with clinical and patient surveys based on Likert's scales. RESULTS: Based on their initial expectations, patients referred to be highly satisfied after PRGF-gel treatment in terms of fine line amelioration, wrinkle reduction, and sagging improvement (overall satisfaction of 8/10). Pre/post-photograph clinical evaluation showed an improvement of 2.5/3 and patients presented a noticeable face rejuvenation due to the soft tissue augmentation effect which was translated into surface texture softening and tone recovery. CONCLUSIONS: Although additional randomized clinical trials should be carried out, this study provides preliminary data supporting the use of PRGF-gel for facial volume restoration.

Pharmacokinetics, safety, and tolerability of olaparib and temozolomide for recurrent glioblastoma: results of the phase I OPARATIC trial.

BACKGROUND: The poly(ADP-ribose) polymerase (PARP) inhibitor olaparib potentiated radiation and temozolomide (TMZ) chemotherapy in preclinical glioblastoma models but brain penetration was poor. Clinically, PARP inhibitors exacerbate the hematological side effects of TMZ. The OPARATIC trial was conducted to measure penetration of recurrent glioblastoma by olaparib and assess the safety and tolerability of its combination with TMZ. METHODS: Preclinical pharmacokinetic studies evaluated olaparib tissue distribution in rats and tumor-bearing mice. Adult patients with recurrent glioblastoma received various doses and schedules of olaparib and low-dose TMZ in a 3 + 3 design. Suitable patients received olaparib prior to neurosurgical resection; olaparib concentrations in plasma, tumor core and tumor margin specimens were measured by mass spectrometry. A dose expansion cohort tested tolerability and efficacy of the recommended phase II dose (RP2D). Radiosensitizing effects of olaparib were measured by clonogenic survival in glioblastoma cell lines. RESULTS: Olaparib was a substrate for multidrug resistance protein 1 and showed no brain penetration in rats but was detected in orthotopic glioblastoma xenografts. Clinically, olaparib was detected in 71/71 tumor core specimens (27 patients; median, 496 nM) and 21/21 tumor margin specimens (9 patients; median, 512.3 nM). Olaparib exacerbated TMZ-related hematological toxicity, necessitating intermittent dosing. RP2D was olaparib 150 mg (3 days/week) with TMZ 75 mg/m2 daily for 42 days. Fourteen (36%) of 39 evaluable patients were progression free at 6 months. Olaparib radiosensitized 6 glioblastoma cell lines at clinically relevant concentrations of 100 and 500 nM. CONCLUSION: Olaparib reliably penetrates recurrent glioblastoma at radiosensitizing concentrations, supporting further clinical development and highlighting the need for better preclinical models.

Unusual Enthalpy Driven Self Assembly at Room Temperature with Chitosan Amphiphiles.

BACKGROUND: GCPQ (N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl- 6-O-glycolchitosan) is a self-assembling polymer being investigated as a pharmaceutical nano-carrier. GCPQ nanoparticles shuttle drugs across biological barriers, improving drug performance. The exact chemistry of GCPQ is varied by the relative proportion of hydrophobic (N-palmitoyl) and hydrophilic (quaternary ammonium) groups and molecular weight. OBJECTIVE: We hypothesised that the thermodynamics of self-assembly is controlled by the polymer molecular weight and hydrophobicity. METHOD: The thermodynamics of self-assembly was investigated using isothermal calorimetry. RESULTS: GCPQs (Mw = 8-15 kDa) formed micellar aggregates at critical micellar concentrations of 1-2.4 µM at 25°C and micellisation was unusually enthalpy driven. There was a positive correlation between ΔHmic and mole% quaternary groups (Q): ΔHmic = 3.8 Q- 159 (r2 = 0.93) and a negative correlation between ΔHmic and molecular weight (Mw): ΔHmic = -13.5 Mw-26.3 (r2 = 0.99). CONCLUSION: These findings provide insights into the positive drivers of stable selfassemblies, namely hydrophobicity and molecular weight, as both hydrophobicity and molecular weight are associated with an increased enthalpy contribution to micellisation.

Nanoparticulate peptide delivery exclusively to the brain produces tolerance free analgesia.

The delivery of peptide drugs to the brain is challenging, principally due to the blood brain barrier and the low metabolic stability of peptides. Exclusive delivery to the brain with no peripheral exposure has hitherto not been demonstrated with brain quantification data. Here we show that polymer nanoparticles encapsulating leucine5-enkephalin hydrochloride (LENK) are able to transport LENK exclusively to the brain via the intranasal route, with no peripheral exposure and nanoparticle localisation is observed within the brain parenchyma. Animals dosed with LENK nanoparticles (NM0127) showed a strong anti-nociceptive response in multiple assays of evoked and on going pain whereas animals dosed intranasally with LENK alone were unresponsive. Animals did not develop tolerance to the anti-hyperalgesic activity of NM0127 and NM0127 was active in morphine tolerant animals. A microparticulate formulation of clustered nanoparticles was prepared to satisfy regulatory requirements for nasal dosage forms and the polymer nanoparticles alone were found to be biocompatible, via the nasal route, on chronic dosing.

The candidate genes TAF5L, TCF7, PDCD1, IL6 and ICAM1 cannot be excluded from having effects in type 1 diabetes.

BACKGROUND: As genes associated with immune-mediated diseases have an increased prior probability of being associated with other immune-mediated diseases, we tested three such genes, IL23R, IRF5 and CD40, for an association with type 1 diabetes. In addition, we tested seven genes, TAF5L, PDCD1, TCF7, IL12B, IL6, ICAM1 and TBX21, with published marginal or inconsistent evidence of an association with type 1 diabetes. METHODS: We genotyped reported polymorphisms of the ten genes, nonsynonymous SNPs (nsSNPs) and, for the IL12B and IL6 regions, tag SNPs in up to 7,888 case, 8,858 control and 3,142 parent-child trio samples. In addition, we analysed data from the Wellcome Trust Case Control Consortium genome-wide association study to determine whether there was any further evidence of an association in each gene region. RESULTS: We found some evidence of associations between type 1 diabetes and TAF5L, PDCD1, TCF7 and IL6 (ORs = 1.05 - 1.13; P = 0.0291 - 4.16 x 10-4). No evidence of an association was obtained for IL12B, IRF5, IL23R, ICAM1, TBX21 and CD40, although there was some evidence of an association (OR = 1.10; P = 0.0257) from the genome-wide association study for the ICAM1 region. CONCLUSION: We failed to exclude the possibility of some effect in type 1 diabetes for TAF5L, PDCD1, TCF7, IL6 and ICAM1. Additional studies, of these and other candidate genes, employing much larger sample sizes and analysis of additional polymorphisms in each gene and its flanking region will be required to ascertain their contributions to type 1 diabetes susceptibility.

Sequencing and association analysis of the type 1 diabetes-linked region on chromosome 10p12-q11.

BACKGROUND: In an effort to locate susceptibility genes for type 1 diabetes (T1D) several genome-wide linkage scans have been undertaken. A chromosomal region designated IDDM10 retained genome-wide significance in a combined analysis of the main linkage scans. Here, we studied sequence polymorphisms in 23 Mb on chromosome 10p12-q11, including the putative IDDM10 region, to identify genes associated with T1D. RESULTS: Initially, we resequenced the functional candidate genes, CREM and SDF1, located in this region, genotyped 13 tag single nucleotide polymorphisms (SNPs) and found no association with T1D. We then undertook analysis of the whole 23 Mb region. We constructed and sequenced a contig tile path from two bacterial artificial clone libraries. By comparison with a clone library from an unrelated person used in the Human Genome Project, we identified 12,058 SNPs. We genotyped 303 SNPs and 25 polymorphic microsatellite markers in 765 multiplex T1D families and followed up 22 associated polymorphisms in up to 2,857 families. We found nominal evidence of association in six loci (P = 0.05 - 0.0026), located near the PAPD1 gene. Therefore, we resequenced 38.8 kb in this region, found 147 SNPs and genotyped 84 of them in the T1D families. We also tested 13 polymorphisms in the PAPD1 gene and in five other loci in 1,612 T1D patients and 1,828 controls from the UK. Overall, only the D10S193 microsatellite marker located 28 kb downstream of PAPD1 showed nominal evidence of association in both T1D families and in the case-control sample (P = 0.037 and 0.03, respectively). CONCLUSION: We conclude that polymorphisms in the CREM and SDF1 genes have no major effect on T1D. The weak T1D association that we detected in the association scan near the PAPD1 gene may be either false or due to a small genuine effect, and cannot explain linkage at the IDDM10 region.

Paracetamol inhibits nitric oxide synthesis in murine spinal cord slices.

Paracetamol is an effective analgesic but its mechanism of action is unclear. We investigated the effect of paracetamol and the analgesic adjuvant caffeine on the activity of NO synthase in mouse spinal cord and cerebellar slices in vitro, by measuring the conversion of [(3)H]arginine to [(3)H]citrulline. Paracetamol (100 microM) had no effect on NO synthase activity in cerebellum, but in the spinal cord both paracetamol (100 microM) and caffeine (30 microM) attenuated glutamate (5 mM)-induced [(3)H]citrulline production and in combination they abolished it. In conclusion paracetamol inhibits spinal cord NO synthesis and this may be related to its analgesic effects.

Polymorphism discovery and association analyses of the interferon genes in type 1 diabetes.

BACKGROUND: The aetiology of the autoimmune disease type 1 diabetes (T1D) involves many genetic and environmental factors. Evidence suggests that innate immune responses, including the action of interferons, may also play a role in the initiation and/or pathogenic process of autoimmunity. In the present report, we have adopted a linkage disequilibrium (LD) mapping approach to test for an association between T1D and three regions encompassing 13 interferon alpha (IFNA) genes, interferon omega-1 (IFNW1), interferon beta-1 (IFNB1), interferon gamma (IFNG) and the interferon consensus-sequence binding protein 1 (ICSBP1). RESULTS: We identified 238 variants, most, single nucleotide polymorphisms (SNPs), by sequencing IFNA, IFNB1, IFNW1 and ICSBP1, 98 of which where novel when compared to dbSNP build 124. We used polymorphisms identified in the SeattleSNP database for INFG. A set of tag SNPs was selected for each of the interferon and interferon-related genes to test for an association between T1D and this complex gene family. A total of 45 tag SNPs were selected and genotyped in a collection of 472 multiplex families. CONCLUSION: We have developed informative sets of SNPs for the interferon and interferon related genes. No statistical evidence of a major association between T1D and any of the interferon and interferon related genes tested was found.

Modulation of paracetamol antinociception by caffeine and by selective adenosine A2 receptor antagonists in mice.

This study investigated the involvement of adenosine receptors in the interaction between paracetamol and caffeine in mice, using the adenosine A2A receptor antagonist 5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine (SCH58261) and the adenosine A2B receptor antagonist 1-propyl-8-p-sulfophenylxanthine (PSB1115), in the tail immersion and hot-plate tests. Paracetamol (10-200 mg/kg) was antinociceptive in both tests, but, in contrast to previous studies, caffeine (10 mg/kg) was pronociceptive in the tail immersion test, and reduced the effects of paracetamol in both tests. SCH58261 (3 mg/kg) was antinociceptive in both tests and in its presence paracetamol (50 mg/kg) had no further effect. PSB1115 (10 mg/kg) had little effect alone but potentiated the effect of paracetamol (50 mg/kg) in the hot-plate test and abolished it in the tail immersion test. These results suggest that adenosine A2B receptors may be involved in the action of paracetamol in a pathway-dependent manner, and also support the existence of pronociceptive adenosine A2A receptors.

Direct in vivo evidence on the mechanism by which nanoparticles facilitate the absorption of a water insoluble, P-gp substrate.

Here we examine the mechanisms by which nanoparticles enable the oral absorption of water-insoluble, P-glycoprotein efflux pump (P-gp) substrates, without recourse to P-gp inhibitors. Both 200nm paclitaxel N-(2-phenoxyacetyl)-6-O-glycolchitosan (GCPh) nanoparticles (GCPh-PTX) and a simulated Taxol formulation, facilitate drug dissolution in biorelevant media, unlike paclitaxel nanocrystals. Verapamil (40mgkg-1) increased the oral absorption from low dose Taxol (6 or 10mgkg-1) by 100%, whereas the oral absorption from high dose Taxol (20mgkg-1) or low dose GCPh-PTX (6 or 10mgkg-1) was largely unchanged by verapamil. There was virtually no absorption from control paclitaxel nanocrystals (20mgkg-1). Imaging of ex-vivo rat ileum samples showed that fluorescently labelled GCPh nanoparticles are mucoadhesive and are taken up by ileum epithelial cells. GCPh nanoparticles were also found to open Caco-2 cell tight junctions. In conclusion, mucoadhesive, drug solubilising GCPh nanoparticles enable the oral absorption of paclitaxel via the saturation of the P-gp pump (by high local drug concentrations) and by particle uptake and tight junction opening mechanisms.

Analysis of the vitamin D receptor gene sequence variants in type 1 diabetes.

Vitamin D is known to modulate the immune system, and its administration has been associated with reduced risk of type 1 diabetes. Vitamin D acts via its receptor (VDR). Four single nucleotide polymorphisms (SNPs) of the VDR gene have been commonly studied, and evidence of association with type 1 diabetes has been reported previously. We sequenced the VDR gene region and developed its SNP map. Here we analyzed association of the 98 VDR SNPs in up to 3,763 type 1 diabetic families. First, we genotyped all 98 SNPs in a minimum of 458 U.K. families with two affected offspring. We further tested eight SNPs, including four SNPs associated with P < 0.05 in the first set and the four commonly studied SNPs, in up to 3,305 additional families from the U.K., Finland, Norway, Romania, and U.S. We only found weak evidence of association (P = 0.02-0.05) of the rs4303288, rs12721366, and rs2544043 SNPs. We then tested these three SNPs in an independent set of 1,587 patients and 1,827 control subjects from the U.K. and found no evidence of association. Overall, our results indicate that common sequence variation in the VDR gene has no major effect in type 1 diabetes in the populations tested.