ABSTRACT
Hair morphology is one of the most differentiated traits among human populations. A previous study has shown that a nonsynonymous single nucleotide polymorphism (SNP) in the EDAR gene, EDAR 1540T/C, is strongly associated with hair thickness in Asian populations. However, the contributions of other genes remain to be elucidated. In this study, 12 SNPs on 10 hair formation-related genes with high differentiation between Asian and other populations were examined to further identify genes associated with hair morphology. A multiple regression analysis adjusted for age, sex, population and the effect of EDAR 1540T/C revealed an SNP in intron 9 of FGFR2, rs4752566, to be significantly associated with hair thickness (cross-sectional area; P-value=0.0052, small diameter; P-value=0.029 and large diameter; P-value=0.0015). In the genomic region containing the FGFR2 gene, rs4752566 was not in strong linkage disequilibrium (LD) with the surrounding SNPs, indicating that the significant association of rs4752566 with the hair thickness is not due to LD with polymorphisms of the other genes. The rs4752566-T allele of FGFR2, associated with thicker hair, was also shown to be associated with higher mRNA level of FGFR2 (P-value=0.0270). These results suggest that the FGFR2 polymorphism affects the variation in hair thickness in Asia through alteration in the expression level of FGFR2.
Subject(s)
Asian People/genetics , Hair/anatomy & histology , Polymorphism, Single Nucleotide/genetics , Receptor, Fibroblast Growth Factor, Type 2/genetics , Genotype , Humans , Linkage Disequilibrium , Lod Score , Polymerase Chain Reaction , RNA, Messenger/genetics , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
Hair morphology is one of the most differentiated traits among human populations. However, genetic backgrounds of hair morphological differences among populations have not been clarified yet. In addition, little is known about the evolutionary forces that have acted on hair morphology. To identify hair morphology-determining genes, the levels of local genetic differentiation in 170 genes that are related to hair morphogenesis were evaluated by using data from the International HapMap project. Among highly differentiated genes, ectodysplasin A receptor (EDAR) harboring an Asian-specific non-synonymous single nucleotide polymorphism (1540T/C, 370Val/Ala) was identified as a strong candidate. Association studies between genotypes and hair morphology revealed that the Asian-specific 1540C allele is associated with increase in hair thickness. Reporter gene assays suggested that 1540T/C affects the activity of the downstream transcription factor NF-kappaB. It was inferred from geographic distribution of 1540T/C and the long-range haplotype test that 1540C arose after the divergence of Asians from Europeans and its frequency has rapidly increased in East Asian populations. These findings lead us to conclude that EDAR is a major genetic determinant of Asian hair thickness and the 1540C allele spread through Asian populations due to recent positive selection.
Subject(s)
Asian People , Edar Receptor/genetics , Hair , Morphogenesis/genetics , Alleles , Evolution, Molecular , Gene Frequency , Humans , Polymorphism, GeneticABSTRACT
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy in humans. The prevalence of G6PD deficiency and its molecular basis were studied in Phuket islanders, Southern Thailand. A total of 345 volunteers (123 males and 222 females) were recruited in this study. Infection with Plasmodium falciparum or Plasmodium vivax was not detected in any of these subjects by polymerase chain reaction (PCR)-based diagnosis. G6PD-deficient individuals were identified with the WST-8/1-methoxy PMS method. The molecular basis of G6PD deficiency was investigated by PCR-direct sequencing procedures or PCR-restriction enzyme fragment length polymorphism assays. The numbers of individuals showing severe and mild G6PD deficiency were 14 and 21, respectively. A high prevalence of G6PD deficiency was observed in subjects with Moken (15.4%) or Thai (15.5%) ethnic background. G6PD Mahidol (487G>A) (n=14), G6PD Viangchan (871G>A) (n=11), G6PD Gaohe (95A>G) (n=2), G6PD Kaiping (1388G>A) (n=1), and G6PD Kerala-Kalyan (949G>A) (n=1) were identified. The results suggest that several groups of people of the Asian Continent, such as Burmese, Laotian or Cambodian, Thai and Chinese, participated in the establishment of the ethnic identity of the current ethnic groups of Phuket Island.
