Qizhi Luo

Association of MICA gene polymorphisms with Chlamydia trachomatis infection and related tubal pathology in infertile women

BACKGROUND The course and morbidity of Chlamydia trachomatis infections are determined by host genetic factors, virulence of the micro-organism and environmental factors. Major histocompatibility complex class I chain-related A (MICA) gene is highly polymorphic as a potential host genetic candidate. The aim of this study was to investigate the association of polymorphic extracellular domains of MICA with C. trachomatis infection and related tubal factor infertility. METHODS Effect of MICA on the susceptibility to C. trachomatis infection and its association with tubal pathology were investigated in 214 infertile women recruited during the period from 2004 to 2007. Subjects were tested for C. trachomatis antibodies, and were further divided into two groups: those with (n = 42) and without (n = 59) tubal pathology based on laparoscopy results. The relationship between prevalence of C. trachomatis, tubal pathology and MICA allele polymorphisms was analysed. RESULTS Women with tubal infertility more often had antibodies to C. trachomatis [66.7 versus 39.1%; odds ratio (OR): 3.12, 95% CI: 1.68-5.78, P = 0.004] than infertile women without tubal pathology. Moreover, allele 008 had a highly negative correlation with C. trachomatis infection (P(c) = 0.0036, OR: 2.14), while other allele polymorphisms showed no significant association with the disease. No statistically significant differences were found in the MICA allele frequencies of C. trachomatis-positive women with or without tubal pathology. CONCLUSIONS The association of a specific MICA allele with C. trachomatis IgG antibodies among women with infertility suggests that the MICA locus might modify host susceptibility to C. trachomatis infection.

MIC gene polymorphism and haplotype diversity in Zhuang nationality of Southern China

Zhuang ethnic minority is the largest minority group in China. Here, we report for the first time the polymorphisms of MICA and MICB in a healthy Zhuang population of 209 unrelated individuals. Using polymerase chain reaction-sequence specific priming (PCR-SSP) and sequencing-based typing (PCR-SBT), 13 MICA-sequence alleles and 5 MICA-STR alleles, as well as 11 MICB alleles were detected, among which MICA(∗)010, MICA(∗)A5 and MICB(∗)005:02 were the most frequent alleles. Linkage disequilibria was investigated and the most common two-locus haplotypes were MICB(∗)005:02-MICA(∗)010 and MICB(∗)014-MICA(∗)045. These results suggest informative genetic markers for investigating origins and evolution of MHC class I region haplotypes in Zhuang population.

Association of MICA gene polymorphisms with liver fibrosis in schistosomiasis patients in the Dongting Lake region

Major histocompatibility complex class I chain-related A (MICA) is a highly polymorphic gene located within the MHC class I region of the human genome. Expressed as a cell surface glycoprotein, MICA modulates immune surveillance by binding to its cognate receptor on natural killer cells, NKG2D, and its genetic polymorphisms have been recently associated with susceptibility to some infectious diseases. We determined whether MICA polymorphisms were associated with the high rate of Schistosoma parasitic worm infection or severity of disease outcome in the Dongting Lake region of Hunan Province, China. Polymerase chain reaction-sequence specific priming (PCR-SSP) and sequencing-based typing (SBT) were applied for high-resolution allele typing of schistosomiasis cases (N = 103, age range = 36.2-80.5 years, 64 males and 39 females) and healthy controls (N = 141, age range = 28.6-73.3 years, 73 males and 68 females). Fourteen MICA alleles and five short-tandem repeat (STR) alleles were identified among the two populations. Three (MICA*012:01/02, MICA*017 and MICA*027) showed a higher frequency in healthy controls than in schistosomiasis patients, but the difference was not significantly correlated with susceptibility to S. japonicum infection (Pc > 0.05). In contrast, higher MICA*A5 allele frequency was significantly correlated with advanced liver fibrosis (Pc < 0.05). Furthermore, the distribution profile of MICA alleles in this Hunan Han population was significantly different from those published for Korean, Thai, American-Caucasian, and Afro-American populations (P < 0.01), but similar to other Han populations within China (P > 0.05). This study provides the initial evidence that MICA genetic polymorphisms may underlie the severity of liver fibrosis occurring in schistosomiasis patients from the Dongting Lake region.

MIC gene polymorphism and haplotype diversity in Li nationality of Southern China.

Here, we report for the first time the polymorphisms of MICA and MICB in a healthy Li population of 344 unrelated individuals. By using polymerase chain reaction-sequence specific priming (PCR-SSP) and sequence-based typing (PCR-SBT), 17 MICA-sequence alleles and 5 MICA-STR (short tandem repeats, STR) alleles, as well as 17 MICB alleles were detected, among which MICA*010, MICA*A4 and MICB*005:02 were the most frequent alleles. In addition, linkage disequilibrium was investigated and the most common two-locus haplotypes were MICB*005:02-MICA*010 and MICB*008-MICA*002:01. These results present informative genetic markers for the investigation of possible origins and the evolution of MHC class I haplotypes in the Li population.

Positive association of major histocompatibility complex class I chain‐related gene A polymorphism with leukemia susceptibility in the people of Han nationality of Southern China

To assess the potential contribution of major histocompatibility complex class I chain-related gene A (MICA) polymorphisms toward the pathogenesis of leukemia, 107 leukemia patients and 162 ethnically matched controls from Hunan province, Southern China, were genotyped for the MICA polymorphism using polymerase chain reaction-sequence-specific priming (PCR-SSP) and sequence-based typing (PCR-SBT). The relevance between these genotypes and risk of leukemia was assessed by means of odds ratio (OR) with 95% confidence intervals (95% CIs). Allele frequencies of MICA-sequence and MICA-STR were different in leukemia patients in comparison with normal controls (both P < 0.05). MICA A5 was directly associated with leukemia (OR = 2.3257, Pc < 0.0005), whereas MICA A5.1 and MICA*008 were inversely associated with leukemia (OR = 0.5874, Pc = 0.0235 and OR = 0.5874, Pc = 0.0329, respectively). In addition, we found that homozygotes for MICA A5 (OR = 14.0659, 95% CI: 3.1627-62.5574, Pc < 0.0001) and MICA*010 (OR = 10.1053, 95% CI: 2.2139-46.1260, Pc < 0.0004) were at an increased risk for leukemia, whereas heterozygotes for MICA*008 and MICA A5.1 were linked to a decreased risk for leukemia (OR = 0.4609, 95% CI: 0.2799-0.7590, Pc = 0.0027). MICA allelic variation is associated with leukemia in Hunan Han population; the data also suggest that MICA gene polymorphism affects susceptibility to different clinical subtypes of leukemia.

Association Between Major Histocompatibility Complex Class I Chain-Related Gene Polymorphisms and Susceptibility of Systemic Lupus Erythematosus

Background: Major histocompatibility complex class I chain‐related gene (MIC) polymorphisms have been associated with many autoimmune diseases. To explore the correlation between MIC polymorphisms and systemic lupus erythematosus (SLE), we compared the sequence of the MIC gene in Han Chinese patients with SLE from Hainan Island, China, with healthy individuals. Methods: In this study, the MIC polymorphisms in 296 subjects (159 patients with SLE and 137 healthy volunteers) of Han ethnicity from Hainan Island were characterized. A chi‐square test was performed to evaluate the differences in the allelic frequency of the MIC genes between patients with SLE and the control subjects. Results: The genotyping results indicated that the frequencies of the MICA*010, MICB*014, and MICB*002 alleles were significantly higher in the control subjects than the patients with SLE. Additionally, the results also indicated that the frequency of the MICB*009N in the SLE group was significantly increased compared to that in the matched control subjects. Conclusions: The results of this study suggested that the MICB*009N allele might be a risk factor for SLE, whereas the MICB*014, MICA*010 and MICB*002 alleles were associated with reduced incidence of SLE in the study population.