Tissue Inhibitor of Metalloproteinase-2 Polymorphisms and Risk for HIV-Associated Neurocognitive Disorder

The imbalance between MMPs and TIMPs is associated with the HIV dissemination tissue damage pathology neurodegenerative disorders, including HAND. Genetic variations in the TIMP gene may modulate the neurocognitive disorder in HIV patients. Hence, we evaluated the genetic variants of TIMP-2 (-418G/C, 303G/A) gene with the risk of HAND. Genotyping of TIMP-2 polymorphism was performed in 50 patients with HAND, 100 no HAND, and 154 healthy controls by PCR-RFLP. TIMP-2 -418GC and 303AA genotypes represented a predominant risk for HAND severity (OR=1.55, P=0.30; OR=4.58, P=0.24). The variant -418CC genotype, -418A allele, had exhibited a significant risk for the acquisition of HAND (OR=12.55, P=0.026; OR=2.66, P=0.004). TIMP-2 303GA, 303AA genotype, and 303A allele evinced a higher risk for HAND severity (OR=1.82, P=0.14; OR=1.70, P=0.63; and OR=1.68, P=0.12). In HIV patients, TIMP-2 -418CC genotype and -418C allele significantly occurred in comparison to healthy controls (OR=10.10, P=0.006; OR=2.02, P=0.009). In the intermediate and early HIV disease stage, TIMP-2 -418CC genotype was significantly increased compared with healthy controls (11.1% vs. 1.3%, OR=14.63, P=0.01; 16.9% vs. 1.3%, OR=14.51, P=0.002). In patients with HAND among tobacco and alcohol users, TIMP-2 -418CC genotype displayed a risk for HAND severity (OR=3.96, P=0.26; OR=4.83, P=0.19). On multivariate logistic regression, TIMP-2 303AA genotype, advanced stage, and gender had a risk for HAND severity (OR=28.98, P=0.02; OR=2.35, P=0.070; and OR=2.36, P=0.04). In conclusion, TIMP-2 -418G/C polymorphism independently, along with alcohol and tobacco, may have an impact on the acquisition of HAND and its severity. TIMP-2 303G/A polymorphism bare a risk for HAND severity.

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Polymorphisms in miRNAs Gene (146a, 149, 196a) and Susceptibility to ARV-associated Hepatotoxicity

Current Genomics ◽

10.2174/1389202920666190325161439 ◽

2019 ◽

Vol 20 (2) ◽

pp. 134-150

Author(s):

Hari Om Singh ◽

Sushma Jadhav ◽

Dharmesh Samani ◽

Tapan N. Dhole

Keyword(s):

Disease Stage ◽

Healthy Controls ◽

Hiv Disease ◽

Hiv Patients ◽

Mirna Genes ◽

Combined Use ◽

Micro Rnas ◽

Functional Consequences ◽

Combined Genotypes ◽

Advanced Hiv Disease

Background: Micro RNAs act as a regulatory layer for pharmacogenomics-related gene expression. It could play a role in the efficacy and toxicity of the drug. The SNPs in miRNA genes are linked with different functional consequences. Methods: Hence, we examined the miR (146a G/C, 149C/T, and 196aC/T) polymorphisms in 34 patients with hepatotoxicity, 123 patients without hepatotoxicity, and 155 healthy controls using a PCRRFLP method. Results: In patients with hepatotoxicity, miR196aCT genotype and combined genotype GCT showed a risk for hepatotoxicity severity with borderline significance (OR=2.08, P=0.07; OR=2.88, P=0.06). While comparing between patients with hepatotoxicity and healthy controls, the combined genotypes CCC and GCT have shown a susceptibility to hepatotoxicity severity (OR=2.89, P=0.05; OR=2.60, P=0.09). The miR196TT genotype was associated with the individuals of advanced HIV disease stage (OR=3.68, P=0.04). In HIV patients who consumed alcohol and did not have hepatotoxicity, the miR 196aCT genotype showed susceptibility to acquisition of hepatotoxicity with borderline significance (OR=2.36, P=0.06). Discussion: The miR149TT and 196aTT genotypes showed a risk of acquisition of hepatotoxicity to nevirapine usage among HIV patients without hepatotoxicity (OR=4.19, P=0.07; OR=1.97, P=0.84). In HIV patients with and without hepatotoxicity, the miR 196aCT genotype showed a risk of acquisition of hepatotoxicity and its severity to the combined use of alcohol and nevirapine, respectively (OR=14.18, P=0.08; OR=2.29, P=0.08). In multivariate logistic regression, taking nevirapine, 196aCT genotype had an independent risk factor for hepatotoxicity severity (OR=5.98, P=0.005; OR=2.38, P=0.05). Conclusion: In conclusion, miR196aC/T polymorphism and combined genotypes GCT and CCC may facilitate the risk for acquisition of hepatotoxicity and its severity.

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Occurrence of Interleukin-2 (330 G/T) Promoter Polymorphism in ARV associated hepatotoxicity

Current Molecular Medicine ◽

10.2174/1566524019666190411093451 ◽

2019 ◽

Vol 19 (3) ◽

pp. 206-215

Author(s):

HariOm Singh ◽

Nayana Nambiar ◽

Dharmesh Samani ◽

Raman R. Gangakhedkar

Keyword(s):

Hepatic Injury ◽

Interleukin 2 ◽

Promoter Polymorphism ◽

Healthy Controls ◽

Hiv Replication ◽

Hiv Patients ◽

Pcr Rflp

Background: IL-2 cytokine is involved in HIV replication and is also known to cause hepatic injury. Polymorphisms in the IL-2 gene are associated with altered interleukin-2 production. Methods: Hence, we assessed the prevalence of IL-2-303G/T polymorphism in 165 HIV patients (34 with and 131without hepatotoxicity) and 155 healthy controls using the PCR-RFLP method. Results: In patients with hepatotoxicity, IL-2-303GT, -303GT+TT genotypes were less prevalent as compared to without hepatotoxicity and healthy controls (29.4% vs. 42.7%, 58.8% vs. 69.5%; 29.4% vs. 40.6%, 58.8% vs. 66.5%, respectively). In patients with hepatotoxicity using tobacco and alcohol, IL-2-303GT,-303TT genotypes were distributed higher as compared to non-users (42.9% vs. 25.9%, OR=8.52, 42.9% vs. 25.9%, OR=9.09, and 28.6% vs. 29.6%, OR=1.63, 42.9% vs. 25.9%, OR=2.93), while IL-2-303TT genotype occurred more often in HIV patients consuming alcohol (34.1% vs. 23.0%). Nevirapine users with hepatotoxicity overrepresented the IL-2-303GT,-303TT genotypes as compared to efavirenz (34.8% vs. 18.2%, OR=4.64, 34.8% vs. 18.2%, OR=3.88). Among nevirapine users, IL-2-303GT genotype was associated with susceptibility to the acquisition of hepatotoxicity with borderline significance (OR=4.24, P=0.06). HIV patients using nevirapine majorly represented the IL-2-303TT genotype (26.9% vs. 25.0%, OR=2.35) while HIV patients with nevirapine + alcohol usage presented the IL-2 -330TT genotype at a higher frequency (34.2% vs. 23.5%, OR=1.51). In patients with hepatotoxicity using nevirapine + alcohol, the genotype IL-2 - 330TT was predominant (60.0% vs. 27.8%, OR=3.16). Conclusion: Thus, IL-2-303G/T polymorphism did not confer the susceptibility to ARV associated hepatotoxicity. However, IL-2-303G/T polymorphism with nevirapine usage may facilitate the risk for acquisition of ARV associated hepatotoxicity.

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TLR7 Polymorphism (rs179008 and rs179009) in HIV-Infected Individual Naïve to ART

Mediators of Inflammation ◽

10.1155/2020/6702169 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

HariOm Singh ◽

Dharmesh Samani ◽

Sumit Aggarwal

Keyword(s):

Infected Individual ◽

Univariate Analysis ◽

Disease Stage ◽

Rapid Decline ◽

Healthy Controls ◽

Single Nucleotide ◽

Codominant Model ◽

Pcr Rflp ◽

Hiv 1 ◽

Cd4t Cell

Toll-like receptors (TLRs) play an important role in the innate immune response to HIV infection. Single nucleotide polymorphism (SNP) in TLR7 (Gln11Leu) gene has been associated with a rapid decline of CD4T cell count. Hence, we assessed the TLR7 (rs179008, Gln11Leu (A/T) and rs179009, IVS2-151 (A/G)) polymorphism in 150 HIV-infected individuals naïve to ART and 158 healthy controls. The genotyping of TLR7 Gln11Leu (A/T) and IVS2-151 (A/G) polymorphisms was done using the PCR-RFLP method. In univariate analysis, none of the genotype and haplotype of TLR7 Gln11Leu (A/T) and IVS2-151 (A/G) polymorphism differed significantly between HIV-infected individuals and healthy controls. The occurrence of TLR7 rs179009AG genotype in the codominant model and rs179009 AG-GG genotype in the dominant model was significantly reduced in HIV-infected individuals as compared to healthy controls (18.0% vs. 29.1%, OR=0.42, P=0.016; 26.7% vs. 36.7%, OR=0.52, P=0.016). TLR7 rs179009AG genotype was significantly underrepresented in the intermediate HIV disease stage compared with healthy controls (OR=0.03, P=0.04). TLR7 rs179009AG genotype expressed higher in tobacco-consuming HIV-infected individuals compared with nonusers (OR=1.71, P=0.47). In conclusion, rs179009 AG-GG and AG genotypes were found reduced in HIV-infected individuals as compared to healthy controls; their higher prevalence in health individuals clearly support that they are associated with reduced risk of acquisition of HIV-1 infection.

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IL-1RN and IL-1βPolymorphism and ARV-Associated Hepatotoxicity

Mediators of Inflammation ◽

10.1155/2018/4398150 ◽

2018 ◽

Vol 2018 ◽

pp. 1-13 ◽

Cited By ~ 3

Author(s):

HariOm Singh ◽

Dharmesh Samani ◽

Vijay Nema ◽

Manisha V. Ghate ◽

R. R. Gangakhedkar

Keyword(s):

Hepatic Injury ◽

Healthy Controls ◽

Severe Hepatotoxicity ◽

Pcr Rflp ◽

Alcohol Users

The severity of hepatic injury depends upon cytokines. Previous studies associatedIL-1RNallele 2 withIL-1βproduction. Hence, we examined the association ofIL-1 RNandIL-1βpolymorphisms with ARV-associated hepatotoxicity. Genotyping ofIL-1RN(VNTR),IL-1β(-511C/T) polymorphisms was done in 162 HIV-infected patients, 34 with ARV hepatotoxicity, 128 without hepatotoxicity, and 152 healthy controls using PCR and PCR-RFLP method. The haplotypes 1T and 2C enhanced the risk for severe hepatotoxicity (OR=1.41,P=0.25;OR=1.67,P=0.31).IL-1β-511TT genotype significantly represented among tobacco using HIV-infected individuals compared to nonusers (OR=3.74,P=0.05).IL-1β-511TT genotype among alcohol users increased the risk for hepatotoxicity (OR=1.80,P=0.90).IL-1β-511CT and-511TT genotypes overrepresented in alcohol using HIV-infected individuals (OR=2.29,P=0.27;OR=2.64,P=0.19).IL-RN2/2 and 1/3 genotypes represented higher in nevirapine using hepatotoxicity patients (OR=1.42,P=0.64,OR=8.79,P=0.09).IL-1β-511CT and-511 TT genotypes among nevirapine users enhanced the risk for severe hepatotoxicity (OR=4.29,P=0.20;OR=1.95,P=0.56).IL-1β-511CT and-511TT genotypes were overrepresented in combined nevirapine and alcohol using HIV-infected individuals as compared to nevirapine users and alcohol nonusers (OR=2.56,P=0.26;OR=2.84,P=0.24).IL-1β-511TT genotype with tobacco, alcohol, and nevirapine usage revealed a trend of risk for the development of ARV-associated hepatotoxicity and its severity.

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No Direct Association of Serotonin Transporter (STin2 VNTR) and Receptor (HT 102T>C) Gene Variants in Genetic Susceptibility to Migraine

Disease Markers ◽

10.1155/2010/280987 ◽

2010 ◽

Vol 29 (5) ◽

pp. 223-229 ◽

Cited By ~ 4

Author(s):

Gunjan Joshi ◽

Sunil Pradhan ◽

Balraj Mittal

Keyword(s):

Genetic Susceptibility ◽

Serotonin Transporter ◽

Serotonin Receptor ◽

Fragment Length Polymorphism ◽

Significant Risk ◽

P Value ◽

Healthy Controls ◽

Pcr Rflp ◽

Direct Association ◽

Polymerase Chain

We aimed to find out if the serotonin receptor (HT102T>C) and serotonin transporter (STin 2) polymorphisms play any role in genetic susceptibility of migraine. For the study, 217 migraine patients and 217 healthy controls (HC) were recruited and genotyping was carried out using the Polymerase Chain Reaction and Restriction Fragment Length polymorphism (PCR-RFLP) method. All results were Bonferroni corrected. We could not find any significant differences in the genotype or allele frequencies in case of HT 102 T>C polymorphism between migraine patients and healthy controls (P value=0.224). No significant association was seen at allele and carrier levels. Sub-grouping the patients on the basis of gender or on basis of migraine type i.e. with or without aura also did not show any association. Similarly, no difference in genotype (P value=0.236), allele (P value=0.550) or carrier frequency (P value=0.771) in STin 2 VNTR polymorphism was observed between migraine patients. However, HT 102 TC genotype was observed to interact significantly with the STin 2.10/10 genotype in enhancing risk of migraine, both with and without aura. In conclusion, the HT102 T>C receptor and the STin 2 VNTR transporter polymorphisms, did not individually confer any significant risk of migraine or its clinical subtypes but the two polymorphisms appear to synergistically influence susceptibility to migraine. Serotonin transporter (STin2 VNTR) and receptor (HT 102T>C) polymorphisms; Migraine with aura (MA); Migraine without aura (MO); Genetic susceptibility

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Preoperative Serum Interleukin-6 Is a Potential Prognostic Factor for Colorectal Cancer, including Stage II Patients

Gastroenterology Research and Practice ◽

10.1155/2016/9701574 ◽

2016 ◽

Vol 2016 ◽

pp. 1-8 ◽

Cited By ~ 6

Author(s):

Kazuyoshi Shiga ◽

Masayasu Hara ◽

Takaya Nagasaki ◽

Takafumi Sato ◽

Hiroki Takahashi ◽

...

Keyword(s):

Colorectal Cancer ◽

Interleukin 6 ◽

Prognostic Significance ◽

Significant Risk ◽

Disease Free Survival ◽

Stage Ii ◽

Disease Stage ◽

Healthy Controls ◽

Preoperative Serum ◽

The Mean

Aims. To evaluate the prognostic significance of serum interleukin-6 (IL-6) in colorectal cancer (CRC).Patients and Methods. Preoperative serum IL-6 was measured in 233 CRC patients and 13 healthy controls. Relationships between IL-6 and various clinicopathological factors were evaluated, and the overall survival (OS) and disease-free survival (DFS) rates according to IL-6 status were calculated for all patients and according to disease stage.Results. The mean IL-6 level was 6.6 pg/mL in CRC patients and 2.6 pg/mL in healthy controls. Using a cutoff of 6.3 pg/mL, obtained using receiver operating characteristic curve analysis, 57 patients had a high IL-6 level. The mean value was higher for stage II disease than for stage III disease. IL-6 status correlated with C-reactive protein (CRP) and carcinoembryonic antigen levels, obstruction, and pT4 disease. The OS differed according to the IL-6 status for all patients, whereas the DFS differed for all patients and for those with stage II disease. The Cox proportional hazards model showed that pT4 disease was an independent risk factor for recurrence in all CRC patients; IL-6, CRP, and pT4 were significant risk factors in stage II patients.Conclusions. The preoperative IL-6 level influences the risk of CRC recurrence.

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Automated Acoustic Analysis of Oral Diadochokinesis to Assess Bulbar Motor Involvement in Amyotrophic Lateral Sclerosis

Journal of Speech Language and Hearing Research ◽

10.1044/2019_jslhr-19-00178 ◽

2020 ◽

Vol 63 (1) ◽

pp. 59-73 ◽

Cited By ~ 3

Author(s):

Panying Rong

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Acoustic Analysis ◽

Speaking Rate ◽

Disease Stage ◽

Healthy Controls ◽

Tongue Movement ◽

Major Barrier ◽

Syllable Repetition ◽

Oral Diadochokinesis ◽

Lateral Sclerosis

Purpose The purpose of this article was to validate a novel acoustic analysis of oral diadochokinesis (DDK) in assessing bulbar motor involvement in amyotrophic lateral sclerosis (ALS). Method An automated acoustic DDK analysis was developed, which filtered out the voice features and extracted the envelope of the acoustic waveform reflecting the temporal pattern of syllable repetitions during an oral DDK task (i.e., repetitions of /tɑ/ at the maximum rate on 1 breath). Cycle-to-cycle temporal variability (cTV) of envelope fluctuations and syllable repetition rate (sylRate) were derived from the envelope and validated against 2 kinematic measures, which are tongue movement jitter (movJitter) and alternating tongue movement rate (AMR) during the DDK task, in 16 individuals with bulbar ALS and 18 healthy controls. After the validation, cTV, sylRate, movJitter, and AMR, along with an established clinical speech measure, that is, speaking rate (SR), were compared in their ability to (a) differentiate individuals with ALS from healthy controls and (b) detect early-stage bulbar declines in ALS. Results cTV and sylRate were significantly correlated with movJitter and AMR, respectively, across individuals with ALS and healthy controls, confirming the validity of the acoustic DDK analysis in extracting the temporal DDK pattern. Among all the acoustic and kinematic DDK measures, cTV showed the highest diagnostic accuracy (i.e., 0.87) with 80% sensitivity and 94% specificity in differentiating individuals with ALS from healthy controls, which outperformed the SR measure. Moreover, cTV showed a large increase during the early disease stage, which preceded the decline of SR. Conclusions This study provided preliminary validation of a novel automated acoustic DDK analysis in extracting a useful measure, namely, cTV, for early detection of bulbar ALS. This analysis overcame a major barrier in the existing acoustic DDK analysis, which is continuous voicing between syllables that interferes with syllable structures. This approach has potential clinical applications as a novel bulbar assessment.

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Comparison of Clinical Outcomes of Persons Living With HIV by Enrollment Status in Washington, DC: Evaluation of a Large Longitudinal HIV Cohort Study (Preprint)

10.2196/preprints.16061 ◽

2019 ◽

Author(s):

Jenevieve Opoku ◽

Rupali K Doshi ◽

Amanda D Castel ◽

Ian Sorensen ◽

Michael Horberg ◽

...

Keyword(s):

Cohort Study ◽

Health Outcomes ◽

Odds Ratio ◽

Adjusted Odds Ratio ◽

Hiv Care ◽

Disease Stage ◽

People Living With Hiv ◽

Hiv Disease ◽

Persons Living With Hiv ◽

Living With Hiv

BACKGROUND HIV cohort studies have been used to assess health outcomes and inform the care and treatment of people living with HIV disease. However, there may be similarities and differences between cohort participants and the general population from which they are drawn. OBJECTIVE The objective of this analysis was to compare people living with HIV who have and have not been enrolled in the DC Cohort study and assess whether participants are a representative citywide sample of people living with HIV in the District of Columbia (DC). METHODS Data from the DC Health (DCDOH) HIV surveillance system and the DC Cohort study were matched to identify people living with HIV who were DC residents and had consented for the study by the end of 2016. Analysis was performed to identify differences between DC Cohort and noncohort participants by demographics and comorbid conditions. HIV disease stage, receipt of care, and viral suppression were evaluated. Adjusted logistic regression assessed correlates of health outcomes between the two groups. RESULTS There were 12,964 known people living with HIV in DC at the end of 2016, of which 40.1% were DC Cohort participants. Compared with nonparticipants, participants were less likely to be male (68.0% vs 74.9%, P<.001) but more likely to be black (82.3% vs 69.5%, P<.001) and have a heterosexual contact HIV transmission risk (30.3% vs 25.9%, P<.001). DC Cohort participants were also more likely to have ever been diagnosed with stage 3 HIV disease (59.6% vs 47.0%, P<.001), have a CD4 <200 cells/µL in 2017 (6.2% vs 4.6%, P<.001), be retained in any HIV care in 2017 (72.9% vs 59.4%, P<.001), and be virally suppressed in 2017. After adjusting for demographics, DC Cohort participants were significantly more likely to have received care in 2017 (adjusted odds ratio 1.8, 95% CI 1.70-2.00) and to have ever been virally suppressed (adjusted odds ratio 1.3, 95% CI 1.20-1.40). CONCLUSIONS These data have important implications when assessing the representativeness of patients enrolled in clinic-based cohorts compared with the DC-area general HIV population. As participants continue to enroll in the DC Cohort study, ongoing assessment of representativeness will be required.

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Physical Activity and Quality of Life in Hemodialysis Patients and Healthy Controls: A Cross-Sectional Study

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18041978 ◽

2021 ◽

Vol 18 (4) ◽

pp. 1978

Author(s):

Tjaša Filipčič ◽

Špela Bogataj ◽

Jernej Pajek ◽

Maja Pajek

Keyword(s):

Quality Of Life ◽

Physical Activity ◽

Everyday Life ◽

Habitual Physical Activity ◽

Healthy Controls ◽

Age And Gender ◽

Comorbidity Score ◽

Sf 36 ◽

And Gender

Hemodialysis (HD) patients have lower functional abilities compared to healthy people, and this is associated with lower physical activity in everyday life. This may affect their quality of life, but research on this topic is limited. Therefore, the present study aimed to determine the relationship between habitual physical activity and quality of life in HD patients and healthy controls. Ninety-three HD patients and 140 controls participated in the study. Quality of life was assessed using a 36-item medical outcomes study short-form health survey (SF-36). Human Activity Profile (HAP) was used to assess habitual physical activity. The adjusted activity score (AAS) from HAP, age, gender, fat tissue index (FTI), lean tissue index (LTI), and Davies comorbidity score were analyzed as possible predictors of the Physical Component Summary (PCS) of the SF-36. Three sequential linear models were used to model PCS. In Model 1, PCS was regressed by gender and age; in Model 2 the LTI, FTI, and Davies comorbidity scores were added. Model 3 also included AAS. After controlling for age and gender (ModelHD 1: p = 0.056), LTI, FTI, and Davies comorbidity score effects (ModelHD 2: p = 0.181), the AAS accounted for 32% of the variation in PCS of HD patients (ModelHD 3: p < 0.001). Consequently, the PCS of HD patients would increase by 0.431 points if the AAS increased by one point. However, in healthy controls, AAS had a lower impact than in the HD sample (B = 0.359 vs. 0.431), while the corresponding effects of age and gender (ModelH 1: p < 0.001), LTI, FTI, and Davies comorbidity score (ModelH 2: p < 0.001) were adjusted for. The proportion of variation in PCS attributed to AAS was 14.9% (ModelH 3: p < 0.001). The current study results showed that physical activity in everyday life as measured by the HAP questionnaire is associated to a higher degree with the quality of life of HD patients than in healthy subjects. Routine physical activity programs are therefore highly justified, and the nephrology community should play a leading role in this effort.

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MICA*019 Allele and Soluble MICA as Biomarkers for Ankylosing Spondylitis in Taiwanese

Journal of Personalized Medicine ◽

10.3390/jpm11060564 ◽

2021 ◽

Vol 11 (6) ◽

pp. 564

Author(s):

Chin-Man Wang ◽

Keng-Poo Tan ◽

Yeong-Jian Jan Wu ◽

Jing-Chi Lin ◽

Jian-Wen Zheng ◽

...

Keyword(s):

Immune Responses ◽

Significant Risk ◽

Significant Risk Factor ◽

Healthy Controls ◽

Hla B27 ◽

Host Immune Responses ◽

Histocompatibility Complex ◽

High Level ◽

Coding Snp

MICA (major histocompatibility complex class I chain-related gene A) interacts with NKG2D on immune cells to regulate host immune responses. We aimed to determine whether MICA alleles are associated with AS susceptibility in Taiwanese. MICA alleles were determined through haplotype analyses of major MICA coding SNP (cSNP) data from 895 AS patients and 896 normal healthy controls in Taiwan. The distributions of MICA alleles were compared between AS patients and normal healthy controls and among AS patients, stratified by clinical characteristics. ELISA was used to determine soluble MICA (sMICA) levels in serum of AS patients and healthy controls. Stable cell lines expressing four major MICA alleles (MICA*002, MICA*008, MICA*010 and MICA*019) in Taiwanese were used for biological analyses. We found that MICA*019 is the only major MICA allele significantly associated with AS susceptibility (PFDR = 2.25 × 10−115; OR, 14.90; 95% CI, 11.83–18.77) in Taiwanese. In addition, the MICA*019 allele is associated with syndesmophyte formation (PFDR = 0.0017; OR, 1.69; 95% CI, 1.29–2.22) and HLA-B27 positivity (PFDR = 1.45 × 10−33; OR, 28.79; 95% CI, 16.83–49.26) in AS patients. Serum sMICA levels were significantly increased in AS patients as compared to healthy controls. Additionally, MICA*019 homozygous subjects produced the highest levels of sMICA, compared to donors with other genotypes. Furthermore, in vitro experiments revealed that cells expressing MICA*019 produced the highest level of sMICA, as compared to other major MICA alleles. In summary, the MICA*019 allele, producing the highest levels of sMICA, is a significant risk factor for AS and syndesmophyte formation in Taiwanese. Our data indicate that a high level of sMICA is a biomarker for AS.

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