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Wei Chen

Publications and source records attributed to Wei Chen.

At least 415 records · Page 23Linked to original sources
PubMed2003

Photoluminescent metal-organic polymer constructed from trimetallic clusters and mixed carboxylates.

The solvothermal reaction of zinc acetate dihydrate with a mixture of benzene-1,4-dicarboxylic acid (H(2)BDC) and benzene-1,3,5-tricarboxylic acid (H(3)BTC) in a solution containing N,N'-dimethylformamide (DMF), absolute ethanol, and chlorobenzene gave rise to a metal-organic polymer, Zn(3).BDC.2BTC.2NH(CH(3))(2).2NH(2)(CH(3))(2). The structure of this polymer possesses a unique three-dimensional framework with tri-zinc clusters, and BDC and BTC units colinking the clusters. Moreover, this metal-organic polymer exhibits strong photoluminescence at room temperature, and the main emission band is at about 430 nm (lambda(ex) = 325 nm). Crystal data for this compound (C(17)H(20)N(2)O(8)Zn(1.5)): monoclinic, space group P2(1)/n, cell dimensions a = 11.6171(3) A, b = 14.2456(4) A, c = 12.6426(3) A, beta = 107.030(2) degrees, V = 2000.51(9) A(3), and Z = 4.

Journal Article↗
PubMed2003

Arene-ruthenium complexes of an acyclic thiolate-thioether and tridentate thioether derivatives resulting from ring-closure reactions.

The reaction of [(eta(6)-arene)RuCl(2)](2) (arene = C(6)Me(6), 1,4-MeC(6)H(4)CHMe(2)) with a large excess of the dianion of bis(2-mercaptoethyl) sulfide, (HSCH(2)CH(2))(2)S, obtained from deprotonation of the dithiol with freshly prepared NaOMe, gives the deep red, monomeric complexes [(eta(6)-arene)Ru(eta(3)-C(4)H(8)S(3))] (arene = C(6)Me(6) (5), 1,4-MeC(6)H(4)CHMe(2) (6)) in which the dianion is bound to the metal atom through one thioether and two thiolate sulfur atoms. Complex 5 reacts with [(eta(6)-C(6)Me(6))RuCl(2)](2) (4) in a 2:1 mole ratio to give a quantitative yield of the chloride salt of a binuclear cation [((eta(6)-C(6)Me(6))Ru)(2)Cl(mu(2)-eta(2):eta(3)-C(4)H(8)S(3))](+) (7) in which the thiolate sulfur atoms of the [(eta(6)-C(6)Me(6))Ru(eta(3)-C(4)H(8)S(3))] group bridge to a (eta(6)-C(6)Me(6))RuCl unit. This compound is also obtained directly from the reaction of 4 with the dithiolate, if the Ru dimer is used in large excess. The binuclear complex [((eta(6)-C(6)Me(6))Ru)(2)(MeCN)(mu(2)-eta(2):eta(3)-C(4)H(8)S(3))](PF(6))(2).MeCN, (9)(PF(6))(2).MeCN, is obtained by treatment of (7)Cl with NH(4)PF(6) in acetonitrile. Protonation of 5 with HCl gave the mono- and diprotonated derivatives viz. [(eta(6)-C(6)Me(6))Ru(eta(3)-C(4)H(9)S(3))]Cl, (8)Cl, and [(eta(6)-C(6)Me(6))Ru(eta(3)-C(4)H(10)S(3))]Cl(2), (10)Cl(2), respectively. The reaction of 5 with methyl iodide gives both the mono- and di-S-methylated derivatives. Treatment of 5 with dibromoalkanes, Br(CH(2))(n)Br (n = 1-5), effects ring closure to give the (eta(6)-C(6)Me(6))Ru dications containing the trithia mesocyclic zS3 (z = 8-12) ligands, isolated as their PF(6) salts. The X-ray crystal structures of 5, 6, the solvates of (7)Cl and (9)(PF(6))(2), and the trithia mesocyclic Ru complexes (eta(6)-C(6)Me(6))Ru(zS3)(PF(6))(2) (z = 8-11) are reported.

Journal Article↗
PubMed2003

Creation of the Chinese visible human data set.

The United States Visible Human Project (VHP) created a digital image data set of complete human male (data acquisition finished in November 1994) and female (data acquisition finished in December 1995) cadavers in magnetic resonance imaging (MRI), computed tomography (CT), and anatomical (anatomic serial section) modes. VHP aroused worldwide enthusiasm for Visible Human Research (VHR), and the data set is being used in a variety of research and educational domains. The Visible Korean Human (VKH) male was produced in March 2001. To accelerate worldwide VHR and to promote virtual anatomy as a revolutionary break with conventional anatomy, more visible human data sets representative of different populations of the world are in demand. The Chinese Visible Human (CVH) male (created in October 2002) and female (created in February 2003) project achieved greater integrity of images, easier blood vessel identification, and were free of organic lesion (unlike the other visible human projects). We performed data acquisition, three-dimensional (3D) reconstruction, and visualization with improved technology to create CVH male and female. CVH is the first volumetric data representing a complete normal adult human male and female of an Asian population. This article presents the history of Chinese Visible Human cadavers and the methods and technology used to produce the data set.

Anatomy, Cross-Sectional↗
PubMed2003

In vivo 31P magnetic resonance spectroscopy of human brain at 7 T: an initial experience.

In vivo (31)P spectra were acquired from the human primary visual cortex at 7 T. The relaxation times of the cerebral metabolites, intracellular pH, rate constant (k(f)) of the creatine kinase (CK) reaction, and nuclear Overhauser enhancement (NOE) on the detected phosphorus moieties from irradiation of the water spins were measured from normal subjects. With a 5-cm-diameter surface coil, 3D (31)P chemical shift imaging was performed with a spatial resolution of 7.5 ml and an acquisition resolution of 8 min, resulting in a signal-to-noise ratio (SNR) for phosphocreatine (PCr) resonance of 32. The apparent T(1) and T(2) of PCr measured at 7 T were 3.37 +/- 0.29 s and 132.0 +/- 12.8 ms, respectively, which were considerably longer than those of adenosine triphosphate (ATP) (T(1): 1.02-1.27 s; T(2): 25-26 ms). The NOE measured in this study was 24.3% +/- 1.6% for PCr, and 10% for ATP. The k(f) measured in the human primary visual cortex was 0.24 +/- 0.03 s(-1). The results from this study suggest that ultra-high-field strength is advantageous for performing in vivo (31)P magnetic resonance spectroscopy (MRS) in the human brain.

Adenosine Triphosphate↗
PubMed2003

Changes in the proton T2 relaxation times of cerebral water and metabolites during forebrain ischemia in rat at 9.4 T.

Proton T(2) relaxation times of cerebral water and metabolites were measured before, during, and after transient forebrain ischemia in rat at 9.4 T using localized proton magnetic resonance spectroscopy ((1)H-MRS) with Hahn echoes formed at different echo times (TEs). It was found that the T(2) values of water and N-acetyl aspartate (NAA) methyl, but not total creatine (tCr) methyl, decrease significantly (approximately 10%) during ischemia, and this T(2) reduction is reversed by reperfusion. The T(2) reduction observed for NAA was most likely caused by the extravascular component of the blood oxygenation level-dependent (BOLD) effect induced by a drastically increased deoxyhemoglobin content during ischemia. The absence of T(2) changes for tCr can probably be explained by the fact that the BOLD-related T(2) decrease was counterbalanced by the conversion of phosphocreatine (PCr) to creatine (Cr), which has a longer T(2) than PCr, during ischemia. The changes in T(2) should be taken into account for the quantification of metabolite concentrations during ischemia.

Animals↗
PubMed2003

Effects of progesterone on growth factor expression in human uterine leiomyoma.

It is now evident that the use of levonorgestrel-releasing intrauterine system (LNg-IUS) is effective for long-term management of menorrhagic women with uterine myomas because of a striking reduction in menorrhagia. This prompted us to characterize the effects of progesterone (P4) on the growth and apoptosis of uterine leiomyoma cells. On the other hand, we have recently noted that epidermal growth factor (EGF) and IGF-I play a crucial role in prompting uterine leiomyoma growth through stimulating the proliferative potential and inhibiting apoptosis of cultured human leiomyoma cells. In the present review, attention was paid to evaluate the effects of P4 on the expression of growth factors (EGF, IGF-I) and apoptosis-related factors (TNFalpha, Bcl-2 protein) in cultured uterine leiomyoma cells. Treatment with P4 augmented EGF and Bcl-2 protein expression, but inhibited IGF-I and TNFalpha expression in cultured leiomyoma cells. It is known that TNFalpha induces apoptosis in a variety of cell types and Bcl-2 protein is an apoptosis-inhibiting gene product. Thus, the results obtained suggest that P4 has dual actions on uterine leiomyoma growth: one is to stimulate leiomyoma cell growth and survival through up-regulating EGF and Bcl-2 protein expression as well as down-regulating TNFalpha expression in those cells, and the other is to inhibit leiomyoma cell growth through down-regulating IGF-I expression in those cells. This may explain why the size of uterine myomas during use of LNg-IUS increases in some but decreases in other instances. This may also explain why the size of uterine myomas during pregnancy does not increase despite the overwhelming increase in circulating concentrations of sex steroid hormones.

Apoptosis↗
PubMed2003

Hepatic lipase promoter C-514T polymorphism influences serial changes in HDL cholesterol levels since childhood: the Bogalusa Heart Study.

Hepatic lipase (HL) is an important determinant of high-density lipoprotein (HDL) concentrations. A common C-to-T substitution at position -514 of the promoter region of the HL gene has been shown to be associated with HL activity and HDL cholesterol (HDL-C) levels. The current study examines the influence of this polymorphism on both levels and serial changes of HDL-C from childhood to adulthood in a community-based sample of 707 white and 291 black unrelated individuals aged 4-38 years using a repeated measures analysis. The frequency of the -514T allele was lower in whites than in blacks (0.228 vs. 0.545, P<0.001). After adjusting for age and BMI, the genotype effect on longitudinal profiles of HDL-C levels was significant (P=0.003) in white males with values in the order of T/T>T/C>C/C. Although a similar trend was seen, the genotype effect was not significant in white females and blacks. Further, the slopes of the age trajectories of HDL-C were similar in three genotype groups in blacks and whites. A sex-genotype interaction effect (P=0.043) on longitudinal profiles of HDL-C levels was found in whites, but not in blacks. White males showed a stronger genotype effect (3.6 mg/dl, P=0.003) than white females (0.5 mg/dl, P=0.601). Thus, the -514T variant of the HL gene is consistently associated with higher levels of HDL-C longitudinally since childhood, but not with rate of change over time. These results suggest that the HL gene may play an important role in the regulation of HDL-C levels from childhood to adulthood, especially in white males.

Adolescent↗
PubMed2003

Analysis of differentially expressed genes in keloids and normal skin with cDNA microarray.

BACKGROUND: Microarray analysis is a popular tool to investigate the function of genes that are responsible for the phenotype of diseases. Keloid is an intricate lesion that is probably modulated by interplay of many genes. We ventured to study the differences of gene expressions between keloids and normal skin with the aid of a cDNA microarray to explore the molecular mechanism underlying keloid formation. MATERIALS AND METHODS: The polymerase chain reaction products of 8400 human genes were spotted on a chip in array. The DNAs were then fixed on the glass plate by a series of treatments. Total RNAs were isolated from freshly excised human keloids and normal skins and then were purified to mRNAs by Oligotex. Both the mRNAs from keloids and normal skins were reversely transcribed to cDNAs with the incorporation of fluorescent dUTP for preparing the hybridization probes. The mixed probes were then hybridized to the cDNA microarray. After highly stringent washing, the cDNA microarray was scanned for the fluorescent signals to display the differences between two kinds of tissues. RESULTS: Among 8400 human genes, there were 402 genes (4.79%) with different expression levels between the keloids and normal skins in all cases, 250 genes, including TGF-beta1 and NGF, were upregulated (2.98%) and 152 downregulated (1.81%). Analyses of collagen, fibronectin, proteoglycan, growth factors, and apoptosis-related molecule gene expression confirmed that our molecular data obtained by cDNA microarray were consistent with the published biochemical and clinical observations of keloids. Higher expression of TGF-beta(1) and NGF in keloids versus normal skins was also testified with reverse transcription polymerase chain reaction method. CONCLUSIONS: DNA microarray technology is an effective technique in screening for differences in gene expression between keloid and normal skin. Many genes are involved in the formation of keloids. Further analysis of the obtained genes will help to understand the molecular mechanism of keloid formation.

Adult↗
PubMed2003

R219K polymorphism of the ABCA1 gene and its modulation of the variations in serum high-density lipoprotein cholesterol and triglycerides related to age and adiposity in white versus black young adults. The Bogalusa heart study.

Mutations in adenosine triphosphate (ATP)-binding cassette transporter 1 (ABCA1) gene have been established as the molecular defect in Tangier disease and familial hypoalphalipoproteinemia, uncommon genetic disorders characterized by deficient or depressed high-density lipoprotein (HDL) cholesterol and increased triglycerides. However, information regarding the frequency of common variants, including Arg219Lys (R219K) within the coding region of the ABCA1 gene and their effect on these phenotypes in the general population is limited. This study examined the frequency and phenotypic effect of R219K variant in a community-based sample of 887 white and 390 black young adults aged 20 to 38 years. The frequency of the variant allele (K219) was higher in blacks than in whites (0.595 v 0.262, P<.001), with carriers (KK+RK) representing 83.8% of blacks versus 44.2% of whites. After adjusting for age, body mass index (BMI), and sex, the genotype effect on HDL cholesterol and natural logarithm of triglycerides was not apparent in whites or blacks. However, significant interaction effects of genotype and age on HDL cholesterol (P<.001) and genotype and BMI on triglycerides (P=.029) were found in whites. Carriers (KK+RK), unlike noncarriers (RR) showed a positive relationship between age and HDL cholesterol (regression coefficient beta=0.28, P=.029 for carriers v beta=-0.18, P=.112 for noncarriers). In addition, the variant allele attenuated the adverse positive relationship between BMI and triglycerides (beta=0.032, P<.001 for carriers v beta=0.046, P<.001 for noncarriers). These results indicate that the K219 allele frequency differs markedly between blacks and whites, and that the variant-allele modulates the association between age and HDL cholesterol, as well as body fatness and triglycerides in a beneficial manner only in whites.

ATP Binding Cassette Transporter 1↗
PubMed2003

Interaction effect of Serine447Stop variant of the lipoprotein lipase gene and C-514T variant of the hepatic lipase gene on serum triglyceride levels in young adults: the Bogalusa Heart Study.

The opposing effects of lipoprotein lipase (LPL) Serin447Stop (S447X) polymorphism and hepatic lipase (HL) C-514T polymorphism on serum triglyceride (TG) levels have been known. However, little is known about the interaction effect of these 2 functional gene variants on serum triglyceride levels. This aspect was examined in a community-based sample of 902 whites and 389 blacks aged 18 to 41 years, using a repeated measures analysis in a mixed model. The frequency of the LPL X447 allele was higher in whites than blacks (16% v 11%, P <.05); whereas the frequency of HL T-514 allele was higher in blacks than whites (77% v 40%, P <.001). The combined genotype distribution was also different between whites and blacks (P <.001). Although the frequency of carriers of both variants was similar in whites and blacks (7% v 8%), more whites carried the LPL X447 allele only (9% v 3%), and more blacks carried the HL T-514 allele only (70% v 33%). Mean levels of TG adjusted for age, sex, and body mass index (BMI) in carriers versus noncarriers of the LPL X447 allele were lower by 13.5% (P <.0001) in whites, 15.8% (P <.01) in blacks and 16.0% (P <.0001) in the total sample. No such phenotypic effect was noted with respect to HL T-514 allele either in blacks or whites, although the mean level in carriers was marginally (P =.08) higher in the total sample. The interaction effect of LPL and HL variants on TG levels was significant in the total sample (P =.016) and marginal in whites (P =.079). In the total sample, the decrease of TG in carriers versus noncarriers of the LPL X447 was 1.8-fold greater in carriers versus noncarriers of the HL T-514 allele (13.6 mg/dL v 7.4 mg/dL, P =.016). Whites tended to show a similar trend (16.8 mg/dL v 6.1 mg/dL, P =.079). Blacks also showed a similar, but nonsignificant, trend (10.4 mg/dL v 8.6 mg/dL, P =.45). These results by showing modulation of association between S447X variant of the LPL gene and serum TG by C-514T variant of the HL gene underscore the importance of gene-gene interactions in the assessment of genetic effects on complex traits.

Adult↗
PubMed2003

Ontogeny and prenatal expression of trefoil factor 3/ITF in the human intestine.

BACKGROUND: Trefoil factor 3 (TFF3) or intestinal trefoil factor (ITF), a peptide normally expressed and secreted by goblet cells at the mucosal surface of the small intestine and colon, is important for the maintenance and repair of the intestinal mucosal barrier. AIM: To study the ontogeny and developmental expression of TFF3 in human intestine. SUBJECTS: We examined TFF3 expression in formalin-fixed and paraffin-embedded intestinal tissues from 24 fetuses (gestational age [GA] 12-23 weeks) and 5 adults by immunohistochemical staining. To determine whether TFF3 is excreted into the fetal intestinal tract, first-passed meconium samples were collected from 43 newborn infants (gestational age 24-41 weeks). The presence of TFF3 was examined by Western blot analysis and the relative levels of TFF3 in the meconium were quantified with a slot blot assay. RESULTS: TFF3 can be detected by immunohistochemistry in human intestine as early as 12 weeks gestation. TFF3 is present in the meconium of newborn infants; no significant difference exists in TFF3 levels in the meconium of premature infants with birth weight (BW) less than 1500 g compared to those with birth weight equal to or more than 1500 g. CONCLUSION: Premature infant's susceptibility to intestinal mucosal injury is unlikely to be explained by developmental expression of TFF3 in human intestine since secreted TFF3 is not deficient in premature infants.

Adult↗
PubMed2003

Geranylgeranyl switching regulates GDI-Rab GTPase recycling.

Rab GTPases, key regulators of membrane targeting and fusion, require the covalent attachment of geranylgeranyl lipids to their C terminus for function. To elucidate the role of lipid in Rab recycling, we have determined the crystal structure of Rab guanine nucleotide dissociation inhibitor (alphaGDI) in complex with a geranylgeranyl (GG) ligand (H(2)N-Cys-(S-GG)-OMe). The lipid is bound beneath the Rab binding platform in a shallow hydrophobic groove. Mutation of the binding pocket in the brain-specific alphaGDI leads to mental retardation. Strikingly, lipid binding acts through a conserved allosteric switching mechanism to promote release of the GDI-Rab[GDP] complex from the membrane.

Diterpenes↗
PubMed2003

Expression of ICAM-1, TNF-alpha, NF kappa B, and MAP kinase in tubers of the tuberous sclerosis complex.

Individuals affected with tuberous sclerosis complex (TSC) develop cortical tubers characterized by disorganized cytoarchitecture and morphologically abnormal cell types, such as dysplastic neurons (DNs) and giant cells (GCs). As part of ongoing cDNA array analysis to study the molecular pathogenesis of tuber formation, we detected increased expression of intercellular adhesion molecule-1 (ICAM-1) mRNA, a cell adhesion molecule (CAM) that functions in cytokine signaling, in tubers. Western and immunohistochemical analyses revealed that ICAM-1 protein was selectively expressed in tubers, but was only minimally expressed in control cortex, adjacent nontuberal cortex, or in non-TSC focal cortical dysplasia. Increased expression of ICAM-1 was found in mice in which the Tsc1 gene was conditionally inactivated in astrocytes. Expression of molecules involved in ICAM-1 activation and cytokine signaling were increased in tubers, including tumor necrosis factor alpha (TNF-alpha), mitogen activated protein kinase (MAPK), and nuclear factor kappa B (NF-kappaB). Numerous CD68-immunoreactive macrophages were observed clustered around GCs further supporting an inflammatory response in tubers. Expression of caspase 8 and Fas support cytokine activation and detection of TUNEL reactivity suggests ongoing cell death in tubers. Specific alterations in ICAM-1, TNF-alpha, NF-kappaB1, and MAPK expression coupled with the detection of numerous CD68-immunoreactive macrophages suggests activation of proinflammatory cytokine signaling pathways in tubers that may culminate in cell death.

Adult↗
PubMed2003

A microstrip transmission line volume coil for human head MR imaging at 4T.

A high-frequency RF volume coil based on the use of microstrip transmission line (MTL) has been developed for in vivo 1H MR applications on the human head at 4T. This coil is characterized by major advantages: (i) completely distributed coil circuit, (ii) high-quality factor (Q), (iii) simple coil structure, and (iv) better sensitivity and less signal-intensity variation in the MR image of the human head compared with an RF shielded birdcage coil of similar coil size. The proposed MTL volume coil does not require additional RF shielding for preventing Q degradation from radiation losses due to the unique MTL structure; thus, it provides a maximal useable space inside the volume coil when compared with most volume coils available at high fields with the same overall coil size. The intrinsic B(1) distribution of the MTL volume coil effectively compensates for the dielectric resonance effect at 4T and improves the signal homogeneity in human head MR images in the transaxial planes. The results of this study demonstrate that the MTL volume coil design provides an efficient and simple solution to RF volume coil design for human MR studies at high fields.

Artifacts↗
PubMed2003

Prognostic value of regional cerebral metabolism in patients undergoing dementia evaluation: comparison to a quantifying parameter of subsequent cognitive performance and to prognostic assessment without PET.

It is difficult to accurately forecast the clinical course of many patients presenting with mild cognitive problems. The utility in prognostic evaluation of various parameters of brain structure and function that can now be noninvasively measured remains to be clearly defined. The present work examined the value of regional cerebral metabolism, assessed with positron emission tomography (PET) and [(18)F]fluoro-2-deoxyglucose, in this context. PET scans of 167 patients (mean Mini-Mental State Examination (MMSE)=24 of 30 possible points) were classified as being positive or negative for evidence of progressive dementia. Results of scans were compared to patients' subsequent clinical course in general and in particular, to their changes in MMSE scores, for up to 10 years following PET. Data were further stratified according to the predictions of referring physicians based upon clinical assessments that had been performed up until the time of PET. Among those patients for whom a progressive dementing course had been predicted by PET criteria (but not those who were predicted by PET criteria to remain stable) a significant decline in general cognitive performance and MMSE scores occurred in the period following PET. Among those patients predicted by clinical criteria to have a progressive dementing illness, 94% of those with positive PET scans did suffer a progressive decline, while only 25% of those with negative scans progressed (relative risk 3.8). Similarly, among those patients who had been predicted by clinical criteria to remain cognitively stable, 74% of those with positive PET scans nevertheless suffered progressive decline, compared with 4% of those with negative PET scans (relative risk 18.4). These data indicate that evaluation of brain metabolism by PET in appropriately selected patients may improve the accuracy of clinical prognostic assessment.

Aged↗
PubMed2003

Screening of human primary melanocytes of defined melanocortin-1 receptor genotype: pigmentation marker, ultrastructural and UV-survival studies.

Recent population studies have demonstrated an association with the red-hair and fair-skin phenotype with variant alleles of the melanocortin-1 receptor (MC1R) which result in amino acid substitutions within the coding region leading to an altered receptor activity. In particular, Arg151Cys, Arg160Trp and Asp294His were the most commonly associated variants seen in the south-east Queensland population with at least one of these alleles found in 93% of those with red hair. In order to study the individual effects of these variants on melanocyte biology and melanocytic pigmentation, we established a series of human melanocyte strains genotyped for the MC1R receptor which included wild-type consensus, variant heterozygotes, compound heterozygotes and homozygotes for Arg151Cys, Arg160Trp, Val60Leu and Val92Met alleles. These strains ranged from darkly pigmented to amelanotic, with all strains of consensus sequence having dark pigmentation. UV sensitivity was found not to be associated with either MC1R genotype or the level of pigmentation with a range of sensitivities seen across all genotypes. Ultrastructural analysis demonstrated that while consensus strains contained stage IV melanosomes in their terminal dendrites, Arg151Cys and Arg160Trp homozygote strains contained only stage II melanosomes. This was despite being able to show expression of tyrosinase and tyrosinase-related protein-1 markers, although at reduced levels and an ability to convert exogenous 3,4-dihydroxyphenyl-alanine (DOPA) to melanin in these strains.

Alleles↗
PubMed2003

The role of melanocortin-1 receptor polymorphism in skin cancer risk phenotypes.

We have examined melanocortin-1 receptor (MC1R) variant allele frequencies in the general population and in a collection of adolescent dizygotic and monozygotic twins to determine statistical associations of pigmentation phenotypes with increased skin cancer risk. This included hair and skin color, freckling, mole count and sun exposed skin reflectance. Nine variants were studied and designated as either strong R (OR = 63; 95% CI 32-140) or weak r (OR = 5; 95% CI 3-11) red hair alleles. Penetrance of each MC1R variant allele was consistent with an allelic model where effects were multiplicative for red hair but additive for skin reflectance. To assess the interaction of the brown eye color gene BEY2/OCA2 on the phenotypic effects of variant MC1R alleles we imputed OCA2 genotype in the twin collection. A modifying effect of OCA2 on MC1R variant alleles was seen on constitutive skin color, freckling and mole count. In order to study the individual effects of these variants on pigmentation phenotype we have established a series of human primary melanocyte strains genotyped for the MC1R receptor. These include strains which are MC1R wild-type consensus, variant heterozygotes, and homozygotes for strong R alleles Arg151Cys and Arg160Trp. Ultrastructural analysis demonstrated that only consensus strains contained stage III and IV melanosomes in their terminal dendrites whereas Arg151Cys and Arg160Trp homozygous strains contained only immature stage I and II melanosomes. Such genetic association studies combined with the functional analysis of MC1R variant alleles in melanocytic cells should provide a link in understanding the association between pigmentary phototypes and skin cancer risk.

Alleles↗