Oculocutaneous albinism (OCA) is a heterogeneous recessive disorder with hypopigmentation in the skin, hair, and eyes. At least 16 genes have been identified as causative genes for human OCA. No comprehensive analysis has been conducted to study the spectral distribution of OCA in Chinese patients. We screened 127 unrelated and unselected Chinese OCA patients for mutations in the TYR, OCA2, TYRP1, SLC45A2, and HPS1 genes. We found that the spectrum of mutational genes and alleles of OCA is population specific. OCA1 is the most common (70.1% of cases) form of Chinese OCA, whereas OCA2, OCA4, and HPS1 account for 10.2%, 12.6%, and 1.6%, respectively. No apparent pathological mutation of TYRP1 has been found. Thirty-eight previously unreported mutational alleles were identified from these OCA patients and were not found in 100 nonalbinism subjects. Of the TYR mutational alleles, 81.1% were clustered on exons 1 and 2. Ten common alleles account for 74.6% of the mutational TYR alleles in Chinese OCA1 patients. The p.D160H allele accounts for 55.6% of the mutational SLC45A2 alleles in Chinese OCA4 patients. These results provide useful information for the establishment of an optimized strategy of gene diagnosis and genetic counseling of Chinese OCA patients.

RFLP (Restriction Fragment Length Polymorphism) is a commonly used technique that can be used for genotyping for nearly all organisms, including plants, animals, and humans. RFLP is widely used in genetic and genomic research, such as genome mapping and gene identification. The technique involves DNA digestion, gel electrophoresis, capillary transfer of DNA, and southern hybridization. In this chapter, we aim to give a detailed introduction of how to perform RFLPs for identifying genotypes.

Objective:To investigate the association between CYP2C19 and ABCB1 polymorphisms and clopidogrel resistance (CR) in patients with cardiovascular disease in Beijing district.Methods:In total, 325 patients were enrolled in the study, including 101 experimental group patients and 224 control group patients. The experimental group was divided into CR group (n=30) and non-CR group (n=71) according to the adenosine diphosphate (ADP)-induced platelet inhibition rate in thromboelastography (TEG) (ADP-induced platelet inhibition rate of <30% was defined as CR and rate of 30%–100% was defined as non-CR). Genotypes, including CYP2C19*2, CYP2C19*3, CYP2C19*4, CYP2C19*5, CYP2C19*17, and ABCB1, were determined using time-of-flight mass spectrometry (Clin-TOF) and Sanger sequencing in all patients.Results:In the experimental group, carriers of CYP2C19 heterozygous (*1/*2, n=46; *1/*3, n=7), and mutation homozygous (*2/*2, n=7; *2/*3, n=3; *3/*3, n=0) genotypes showed significantly lower ADP-induced platelet inhibition rates than noncarriers (*1/*1, n=38; p=0.035 and 0.001, respectively); the carriage of mutant CYP2C19*2 or *3 allele was significantly associated with an increased risk of CR. In contrast, carriers of ABCB1 heterozygous (TC, n=50) showed significantly lower ADP-induced platelet inhibition rates than noncarriers (CC, n=39, p=0.097), and there was no significant correlation between ABCB1 genotypes and higher CR risk.Conclusion:The carriage of CYP2C19*2 or *3 mutant allele was significantly associated with attenuated platelet response to clopidogrel and increased CR risk. The carriage of ABCB1 mutant allele was not significantly associated with CR risk.

Warfarin is the most common oral anticoagulant. Because of a narrow therapeutic range, interindividual differences in drug responses, and the risk of bleeding, there are many challenges in using warfarin. We need to predict the warfarin maintenance dose. However, ethnic-specific algorithms may be required, and some Chinese algorithms do not perform adequately. Therefore, we aimed to establish a Han Chinese appropriate algorithm.We recruited a study group consisting of 361 Han Chinese patients receiving warfarin treatment who had heart valve replacements. Genotyping of 38 single nucleotide polymorphisms (SNPs) in 13 candidate genes was carried out using the MassARRAY. In the derivation cohort, a multiple linear regression model was constructed to predict the warfarin dosage. We evaluated the accuracy of our algorithm in the validation cohort and compared it with the other 5 algorithms based on Han Chinese and other races.We established a Han Chinese-specific pharmacogenetic-guided warfarin dosing algorithm. Warfarin maintenance dosage (mg/day) = 1.787 − 0.023 × (Age) + 1.151 × (BSA [m2]) + 0.917 × (VKORC1 AG) + 4.619 × (VKORC1 GG) + 0.595 × (CYP4F2 TT) + 0.707 × (CYP2C19 CC). It explained 58.3% of the variance in warfarin doses in Han Chinese patients and was superior to the other 5 algorithms. The ability of the 6 algorithms which estimate the required dose correctly was tested. Our model had a mean absolute error of 0.74 mg/day, the other 5 models have mean absolute error of 0.81 mg/day,1.05 mg/day, 1.24 mg/day, 1.18 mg/day, and 0.85 mg/day, respectively. Our model had a mean percentage error of 26.9%, the other 5 models have the mean percentage error of 27.7%, 27.2%, 52.3%, 45.7%, and 29.3%, respectively.Physicians can not adopt algorithm from other race directly to predict warfarin dose in patients with heart valve replacements, they should establish a new algorithm or adjust another algorithm to fit their patients. The algorithm established in this study has the potential to assist physicians in determining warfarin doses that are close to the appropriate doses.