Danai Tiwawech

Human mtDNA and Y-chromosome variation is correlated with matrilocal versus patrilocal residence

Genetic differences among human populations are usually larger for the Y chromosome than for mtDNA. One possible explanation is the higher rate of female versus male migration due to the widespread phenomenon of patrilocality, in which the woman moves to her mates residence after marriage. To test this hypothesis, we compare mtDNA and Y-chromosome variation in three matrilocal (in which the man moves to his mates residence after marriage) and three patrilocal groups among the hill tribes of northern Thailand. Genetic diversity in these groups shows a striking correlation with residence pattern, supporting the role of sex-specific migration in influencing human genetic variation.

Recent Origin and Cultural Reversion of a Hunter–Gatherer Group

Contemporary hunter–gatherer groups are often thought to serve as models of an ancient lifestyle that was typical of human populations prior to the development of agriculture. Patterns of genetic variation in hunter–gatherer groups such as the !Kung and African Pygmies are consistent with this view, as they exhibit low genetic diversity coupled with high frequencies of divergent mtDNA types not found in surrounding agricultural groups, suggesting long-term isolation and small population sizes. We report here genetic evidence concerning the origins of the Mlabri, an enigmatic hunter–gatherer group from northern Thailand. The Mlabri have no mtDNA diversity, and the genetic diversity at Y-chromosome and autosomal loci are also extraordinarily reduced in the Mlabri. Genetic, linguistic, and cultural data all suggest that the Mlabri were recently founded, 500–800 y ago, from a very small number of individuals. Moreover, the Mlabri appear to have originated from an agricultural group and then adopted a hunting–gathering subsistence mode. This example of cultural reversion from agriculture to a hunting–gathering lifestyle indicates that contemporary hunter–gatherer groups do not necessarily reflect a pre-agricultural lifestyle.

Prevalence of hepatitis B and C virus infection in rural ethnic populations of Northern Thailand.

BACKGROUND In Thailand, the population is composed of multiethnic stocks. However, many epidemiological studies on HBV and HCV have focused on blood donors with Thai and/or Chinese ethnic background. Available information on HBV and HCV infections among ethnic minorities in Thailand is limited. OBJECTIVE So as to contribute to the local public health planning, we have conducted an ethno-epidemiological survey for the HBV and HCV infections among several minorities in a multiethnic center, Northern Thailand. STUDY DESIGN A total of 658 individuals from seven ethnic groups, Lahu, Lisu, Shan, Red Karen, White Karen, Hmong and Akha, living in northern Thailand were studied for the prevalence of HBV and HCV infections by the use of particle agglutination tests. RESULTS An overall prevalence of HBs-Ag, anti-HBs and anti-HCV in the seven groups was 10.3, 33.0 and 3.8%, respectively. The positivity rate of HBV and HCV infection in each tribe ranged 4.7% (Akha)-22.6% (Lahu) and 2.0% (Hmong and Akha)-8.1% (Shan), respectively. Sexual difference in the prevalence of HBV was not observed, whereas the prevalence of HCV was significantly higher in the males (P<0.05). The prevalence of HBV was significantly different (P<0.005) by the groups but that of HCV was not. CONCLUSIONS The prevalence of HBV and HCV infection in Thai ethnic minorities was investigated. We demonstrated that HBV was a more common infectious agent found in this populations than HCV. The prevalence of HBV infection was different by tribe but not by sex. In contrast, the prevalence of HCV infection was not different by tribe but by sex (males were infected more than females). The present study showed that HBV and HCV infection are widely spread in rural ethnic populations of northern Thailand. Thus, a nation wide but community-base epidemiological survey is required for the public health planning to control their related serious diseases.

Hypermethylation of suppressor of cytokine signaling 1 in hepatocellular carcinoma patients.

Hepatocellular carcinoma (HCC), the most common primary hepatic tumor, is highly prevalent in the Asia-Pacific region, including Thailand. Many genetic and epigenetic alterations in HCC have been elucidated. The aim of this study was to determine whether aberrant methylation of the suppressor of cytokine signaling 1 gene (SOCS1) occurs in HCCs. Methylation specific-PCR assays were performed to identify the methylation status of SOCS1 in 29 tumors and their corresponding normal liver tissues. An abnormal methylation status was detected in 17 (59%), with a higher prevalence of aberrant SOCS1 methylation significantly correlating with HCC treated without chemotherapy (OR=0.04, 95%CI=0.01-0.31; P=0.001). This study suggests that epigenetic aberrant SOCS1 methylation may be a predictive marker for HCC patients.

Alu Methylation in Serum from Patients with Nasopharyngeal Carcinoma

BACKGROUND Nasopharyngeal carcinoma (NPC) is a common cancer in Southern China and Southeast Asia. Alu elements are among the most prevalent repetitive sequences and constitute 11% of the human genome. Although Alu methylation has been evaluated in many types of cancer, few studies have examined the levels of this modification in serum from NPC patients. OBJECTIVE To compare the Alu methylation levels and patterns between serum from NPC patients and normal controls. MATERIALS AND METHODS Sera from 50 NPC patients and 140 controls were examined. Quantitative combined bisulfite restriction analysis-Alu (qCOBRA-Alu) was applied to measure Alu methylation levels and characterize Alu methylation patterns. Amplified products were classified into four patterns according to the methylation status of 2 CpG sites: hypermethylated (methylation at both loci), partially methylated (methylation of either of the two loci), and hypomethylated (unmethylated at both loci). RESULTS A comparison of normal control sera with NPC sera revealed that the latter presented a significantly lower methylation level (p=0.0002) and a significantly higher percentage of hypomethylated loci (p=0.0002). The sensitivity of the higher percentage of Alu hypomethyted loci for distinguishing NPC patients from normal controls was 96%. CONCLUSIONS Alu elements in the circulating DNA of NPC patients are hypomethylated. Moreover, Alu hypomethylated loci may represent a potential biomarker for NPC screening.

Anthropological implication of the SDF1 -3′A allele distribution in Southeast Asia and Melanesia

AbstractThe distribution of the SDF1-3′A allele among 1848 individuals in Southeast Asia and Melanesia was studied with the polymerase chain reaction-restriction fragment length polymorphism assay. The SDF1-3′A allele frequency in the populations of mainland Southeast Asia ranged from 0.0 to 0.355, whereas in the populations of insular Southeast Asia and Melanesia, it ranged from 0.233 to 0.733, with an increasing cline from west to east. Correlation between SDF1-3′A frequency and longitude values was highly significant for the populations in the Pacific region (r = 0.867, P < 0.001). The geographic distribution of the SDF1-3′A frequencies in the Pacific region was interpreted by an admixture of Austronesians with the aboriginal people in situ. In addition, this study found high proportions of SDF1-3′A/3′A homozygous individuals in several populations, which will enable us to evaluate roles of the SDF1 genotypes in SDF-1 expression.

Association between ERCC1 Polymorphism and the Risk and Clinicopathological Features of Breast Cancer in Thai Women in the Lower Northeastern Region

Background: Breast cancer is a major public health problem around the world, including Thailand and it has the highest ranking among female cancer. Currently, the diversity or polymorphism of ERCC1 gene (excision repair cross-complementary group 1 gene or ERCC1) was reported to associate with an increased risk of breast cancer. This study aims to investigate the relationship between ERCC1 polymorphism and the breast cancer risk in the lower northeastern region women of Thailand. Materials and Methods: One hundred fifty one samples from breast cancer patients and 120 samples from healthy control group were analysed. Genomic DNA was extracted from white blood cell of all samples. The real-time polymerase chain reaction (qPCR) was used to demonstrate genetic polymorphism of ERCC1. Results: The results showed that the ERCC1 rs11615 polymorphism variant AG was associated with an increased risk of breast cancer. This study demonstrated that the frequency of ERCC1 rs11615 in patients with breast cancer was higher than healthy control group. The ERCC1 polymorphism variant AG carrier presented 3.53-folds high risk of breast cancer [odds ratio (OR) = 3.53, 95% CI = 1.61-7.74, P = 0.001]. In addition, when age, menopause period, number of child, smoking and alcohol drinking were adjusted, the ERCC1 rs11615 variant AG carrier was associated with increased breast cancer risk to 3.97 folds, with OR = 3.79, 95% CI = 1.62-8.84, P = 0.002. Conclusions: This study showed that ERCC1 rs11615 genotype AG was associated with breast cancer risk in the lower northeastern region women of Thailand.

Clinicopathological Significance of BRCA1 Promoter Hypermethylation in Thai Breast Cancer Patients

Breast cancer susceptibility gene 1 (BRCA1), mapped on chromosome 17q21, is implicated in the mechanisms of cellular DNA repair. Inactivation of this gene is involved in the development of many human cancers, including breast cancer. This study aimed to investigate the prognostic value of BRCA1 promoter hypermethylation and expression in breast cancer cases. Sixty-one breast cancers were examined for BRCA1 hypermethylation by methylation-specific polymerase chain reaction (PCR), and 45 paired normal breast tissues were analyzed for altered BRCA1 mRNA levels by quantitative real-time reverse transcription-polymerase chain reaction (qRT- PCR). Aberrant methylation status in BRCA1 was detected in 15 of 61 cases (24.6%), while reduced expression was found in 7 of 45 (15.6%). BRCA1 hypermethylation was statistically associated with tumor grade III (p=0.04), a high frequency of stage IIB (p=0.02), and triple-negative phenotype (OR= 3.64, 95%CI =1.1-12.3, p=0.03). Our findings indicated that BRCA1 promoter hypermethylation is a useful prognostic marker for breast cancer.