Genetic diversity of KELnull and KELel: a nationwide Austrian survey.

BACKGROUND: Besides ABO and RH, the KEL blood group system, including the two antithetical antigens KEL1 and KEL2, is the most important owing to the frequent appearance of anti-KEL alloantibodies and their considerable clinical significance. So far, only limited information was available on KEL variant alleles determining the rare silent KELnull and KELel phenotypes with absent or diminished KEL antigen expression detected only by adsorption-elution techniques, respectively. STUDY DESIGN AND METHODS: For a systematic investigation of the KELnull and KELel phenotypes, 401 KEL:1,-2 samples (representing 2.6% of all Austrian KEL:1,-2 samples) and 811 KEL:1,2 samples were genotyped for the KEL*1/KEL*2-specific single-nucleotide polymorphism. All heterozygous KEL*1/KEL*2 and 4 additional KELnull samples were subjected to detailed immunohematologic examination and allele-specific sequencing. RESULTS: In 14 KEL:1,-2 samples, discrepant KEL*1/KEL*2 heterozygosity was observed, indicating the presence of silent or barely expressed KEL*2 alleles, whereas all KEL:1,2 individuals were homozygous for KEL*2. In the course of further molecular analysis, 8 novel KEL*2null and 2 KEL*2el alleles were discovered, representing 67 and 33 percent of previously known KEL*2null- and KEL*2el-encoding alleles, respectively. In addition, two different known KEL*2null and KEL*2el alleles each were confirmed. The immunohematologic properties of KEL variant red blood cells were defined by extended KEL phenotyping and flow cytometric KEL1, KEL2, KEL4, and KEL7 antigen as well as total Kell protein quantification. CONCLUSION: For the first time, exact KELnull and KELel population frequencies could be established in this population.

Is atherosclerosis in diabetes and impaired fasting glucose driven by elevated LDL cholesterol or by decreased HDL cholesterol?

OBJECTIVE: To evaluate the atherogenicity of lipids in coronary patients with normal fasting glucose (NFG), impaired fasting glucose (IFG), and type 2 diabetes. RESEARCH DESIGN AND METHODS: Serum lipid values, the presence of angiographic coronary artery disease (CAD) at baseline, and the incidence of vascular events over 2.3 years were recorded in 750 consecutive patients undergoing coronary angiography. RESULTS: Triglycerides significantly (P < 0.001) increased and HDL cholesterol (P < 0.001) as well as LDL particle diameter (P < 0.001) significantly decreased from subjects with NFG <5.6 mmol/l (n = 272) over patients with IFG > or =5.6 mmol/l (n = 314) to patients with type 2 diabetes (n = 164). Factor analysis revealed two factors in the lipid profiles of our patients: triglycerides, HDL cholesterol, apolipoprotein A1, and LDL particle diameter loaded high on an HDL-related factor, and total cholesterol, LDL cholesterol, and apolipoprotein B loaded high on an LDL-related factor. In patients with type 2 diabetes, the HDL-related factor (odds ratio 0.648 [95% CI 0.464-0.904]; P = 0.011), but not the LDL-related factor (0.921 [0.677-1.251]; P = 0.597), was associated with significant coronary stenoses > or =50%. Consistently, in the prospective study, the HDL-related factor (0.708 [0.506-0.990]; P = 0.044), but not the LDL-related factor (1.362 [0.985-1.883]; P = 0.061), proved significantly predictive for vascular events in patients with type 2 diabetes. CONCLUSIONS: The low HDL cholesterol/high triglyceride pattern is associated with the degree of hyperglycemia. In coronary patients with type 2 diabetes, this pattern correlates with the prevalence of CAD and significantly predicts the incidence of vascular events.