Hosik Seok

Association between interleukin 18 polymorphisms and alopecia areata in Koreans.

Interleukin 18 (interferon gamma-inducing factor) (IL18) is an important proinflammatory cytokine that belongs to the IL1 family. This study investigated whether IL18 single-nucleotide polymorphisms (SNPs) are associated with the susceptibility to alopecia areata (AA) in a Korean population. Two hundred thirty-three AA patients and 243 healthy control subjects were recruited. One promoter SNP (rs187238, -137G/C) and exonic SNP (rs549908, Ser35Ser) in IL18 were genotyped using direct sequencing. SNPStats, SPSS 18.0, and Haploview version 4.2 programs were used to evaluate genetic data. Multiple logistic regression models were used to determine odds ratios, 95% confidence intervals, and P values. Tested 2 SNPs (rs187238 and rs549908) were associated with the development of AA (rs187238, P=0.002 in a codominant model 1, P=0.0048 in a dominant model, P=0.02 in a log-additive model, P=0.023 in allele distribution; rs549908, P=0.003 in a codominant model 1, P=0.0052 in a dominant model, P=0.016 in a log-additive model, P=0.015 in allele distribution). Our data suggest that the IL18 may be a risk factor for AA susceptibility.

Association between TLR1 polymorphisms and alopecia areata

Abstract Toll-like receptors (TLRs) may contribute to the process of autoimmune attacks on hair follicles. To investigate whether the TLR1 gene polymorphisms are associated with the development and clinical features of alopecia areata (AA), a case-control comparison of two single nucleotide polymorphisms (SNPs) (rs4833095, Asn248Ser and rs5743557, −414C > T) of TLR1 were studied in 239 AA patients and 248 controls. Using multiple logistic regression model, odds ratios, 95% confidence intervals and corresponding p values were estimated. Clinical features were analyzed based on the age of onset, family history, type of AA, nail involvement and body hair involvement. The missense SNP rs4833095 was significantly associated with the development of AA (codominant2, p = 0.002; recessive, p = 0.001; log-additive, p = 0.0071; and allele frequency, p = 0.0066). The promoter SNP rs5743557 was weakly associated with the development of AA (codominant2, p = 0.019; recessive, p = 0.032; log-additive, p = 0.020; and allele frequency, p = 0.03). In the clinical features, rs4833095 was only weakly associated with age of onset between 15 and 50 years (codominant2, p = 0.043 and recessive, p = 0.022). The results suggest that rs4833095 of TLR1 may be associated with the susceptibility for AA in the Korean population.

Association studies of cytochrome P450, family 2, subfamily E, polypeptide 1 (CYP2E1) gene polymorphisms with acute rejection in kidney transplantation recipients.

Recent studies have shown that single‐nucleotide polymorphisms (SNPs) are associated with allograft rejection in kidney transplantation recipients. We evaluated the possible association between SNPs of the cytochrome P450, family 2, subfamily E, polypeptide 1 (CYP2E1) gene, and acute rejection (AR) among renal transplant patients in a Korean population. We conducted a case–control association study in 63 AR and 284 non‐AR kidney transplant recipients. The SNPs of CYP2E1 were genotyped by direct sequencing. Recipient sex (p = 0.023) and the use of tacrolimus (p = 0.017) were significantly different between the two groups. The use of mycophenolate mofetil (MMF) and antibody induction therapy was significantly lower in the AR group. Multiple logistic regression models (codominant, dominant, recessive, and log‐additive models) adjusted by sex and type of immunosuppressive regimens were applied to determine the odds ratios (ORs), 95% confidence intervals (CIs), and p‐values. The rs2515641 of CYP2E1 showed significant differences between the AR patient group and non‐AR group (p = 0.003, OR = 2.55, 95% CI = 1.37–4.75 in the codominant 1 model; p = 0.002, OR = 2.61, 95% CI = 1.43–4.77 in the dominant model; p = 0.0035, OR = 2.13, 95% CI = 1.29–3.50 in the log‐additive model). The allele of the rs2515641 SNP also showed a significant association (p = 0.004, OR = 1.99, 95% CI = 1.24–3.21). This study suggests that the CYP2E1 polymorphism may be related to the development of AR in Korean kidney transplantation recipients.

Association of BID SNPs (rs8190315 and rs2072392) and clinical features of benign prostate hyperplasia in Korean population.

Exercise has beneficial effect on cancer apoptosis and benign prostatic hyperplasia (BPH). The BH3 interacting domain death agonist (BID) gene expression is associated with apoptosis or cell proliferation. In this study, we investigated the association between BID single nucleotide polymorphisms (SNPs) and the development, prostate volume, and international prostate symptom score (IPSS) of BPH. In 222 BPH males and 214 controls, two SNPs in BID [rs8190315 (Ser56Gly), and rs2072392 (Asp106Asp)] were genotyped and analyzed using multiple logistic regression models. In the result, the genotype and allele frequencies of rs8190315 and rs2072392 were not associated with BPH development or IPSS, however, the allele frequencies [odd ratio (OR)= 1.90, 95% confidence interval (CI)= 1.07–3.41, P= 0.03] and genotype frequencies (in dominant model, OR= 1.94, 95% CI= 1.01–3.74, P= 0.42) of rs8190315, and the genotype frequencies of rs2072392 (in dominant model, OR= 1.94, 95% CI= 1.01–3.74, P= 0.42) were associated with increased prostate volume. We propose that rs8190315 and rs2072392 of BID may contribute to the disease severity of BPH.

Association of a Missense ALDH2 Single Nucleotide Polymorphism (Glu504Lys) With Benign Prostate Hyperplasia in a Korean Population

Purpose Aldehyde dehydrogenase 2 (ALDH2) is a well-known gene involved in alcohol and aldehyde metabolism. Moreover, recent studies have reported associations between ALDH2 and age-related disorders. Benign prostate hyperplasia (BPH) is an age-related disorder and genetic factors may contribute to its onset. In this study, we investigated the association of a well-studied ALDH2 single nucleotide polymorphism (SNP), rs671, with the onset and clinical features of BPH. Methods A total of 222 BPH patients and 214 control subjects were genotyped. The clinical features of the BPH patients (prostate volume, prostate-specific antigen level, and International Prostatic Symptom Score) were analyzed. Results The results show that rs671 was only associated with the volume of BPH in genotype and allele frequencies (P<0.05). Conclusion We propose that rs671 is an Asian-specific SNP in ALDH2 that may affect the disease progression of BPH in the Korean population.

Association Between Secretoglobin Family 3A Member 2 (SCGB3A2) Gene Polymorphisms and Asthma in a Korean Population

Background Secretoglobin family 3A member 2 (SCGB3A2) plays an important role in secreting lung surfactant protein, which is a downstream target of thyroid transcription factor. Material/Methods We investigated whether single-nucleotide polymorphisms (SNPs) of SCGB3A2 gene contribute to susceptibility to asthma. To explore this possible association, 2 promoter SNPs (rs6882292, 659 G/A and rs1368408, −112 G/A) and missense SNP (rs151333009, stop codon) were tested in SCGB3A2 gene in 101 asthma patients and 377 healthy control subjects. SNPStats was used to obtain odds ratio (OR), 95% confidence intervals (CI), and P value adjusted for age and sex as covariables. Logistic regression method in each model (dominant, recessive, and log-additive) was applied to analyze genetic data. Results rs151333009 SNP showed a monomorphic genotype. Two promoter SNPs (rs6882292, −659 G/A and rs1368408, −112 G/A) showed significant association with asthma (rs6882292, OR=2.66, 95% CI=1.42–5.01, p=0.0033 in dominant model, OR=2.45, 95% CI=1.33–4.54, p=0.0055 in log-additive model; rs1368408, OR=1.59, 95% CI=1.02–2.49, p=0.041 in dominant model, OR=3.02, 95% CI=1.15–7.90, p=0.03 in recessive model, OR=1.63, 95% CI=1.63, 95% CI=1.12–2.37, p=0.012 in log-additive model). Conclusions These results suggest that the promoter SNPs (rs6882292 and rs1368408) of SCGB3A2 gene may contribute to susceptibility to asthma in a Korean population.

Association of HSPA1B SNP rs6457452 with Alopecia Areata in the Korean Population

The heat shock 70 kDa protein 1B (HSPA1B), which has been well-studied among the famous heat shock proteins HSPA1A/B/L, is related to autoimmune diseases, including Alopecia Areata (AA). In this study, the association of a 5’-untranslated region (5’UTR) SNP rs6457452 and a promoter SNP rs2763979 (‐1140C > T) of HSPA1B with AA was investigated in 236 controls and 228 AA patients. Statistical analyses using the multiple logistic models were done, according to the onset and the clinical features of AA, including the age of onset, family history, type of AA lesion, nail involvement and body hair involvement. The results showed that rs6457452 was associated with the onset of AA (p < 0.002). In the analysis of clinical features of AA, rs6457452 was weakly related to the age of onset (p ≤ 0.04) and that rs2763979 was only weakly related to the type of AA lesion (p = 0.041). In conclusion, we suggest that the 5’UTR SNP rs6457452 of HSPA1B may be associated with the onset of AA and the T allele of rs6457452 may confer the reduced susceptibility to AA in the Korean population.