What is the prevalence of C (Rh) negativity in the general population?

Prevalence of Rh C Negativity in the General Population

The prevalence of C (Rh) negativity in the general population is approximately 20%, with significant variations among different ethnic groups.

Blood Group Inheritance and Rh Factor System

The Rh blood group system is complex and includes multiple antigens beyond just the commonly known D antigen (Rh positive/negative). The major Rh antigens include:

• RhD (the primary Rh factor that determines Rh+ or Rh-)
• RhC/c
• RhE/e

These antigens are encoded by two closely related genes:

• RHD gene: encodes the D antigen
• RHCE gene: encodes the C/c and E/e antigens 1

Genetic Basis

• The Rh factor is determined by a single gene with two alleles: Rh positive (D) and Rh negative (d), with Rh positive being dominant 2
• The RHCE gene has multiple alleles (RHce, RHCe, RHcE, and RHCE) that determine the expression of C/c and E/e antigens 1
• These genes are located on chromosome 1p34-p36 and likely derived from duplication of a common ancestral gene 3

Distribution of C Antigen Negativity

The prevalence of C negativity varies significantly by ethnicity:

• In Caucasian populations: approximately 20% are C-negative
• In African and African-American populations: approximately 32-40% are C-negative
• In Asian populations: approximately 30% are C-negative

This distribution pattern is important clinically, particularly in transfusion medicine and maternal-fetal medicine.

Clinical Significance of C Negativity

Transfusion Medicine

C negativity is clinically significant in transfusion medicine, particularly for patients who require multiple transfusions:

• The American Society of Hematology (ASH) recommends prophylactic red cell antigen matching for Rh (C, E or C/c, E/e) and K antigens for patients with sickle cell disease receiving transfusions 4
• This recommendation is based on the fact that antibodies against C, E, and K antigens are among the most common antibodies complicating transfusion 4

Pregnancy and Alloimmunization

C negativity becomes important in pregnancy when there's potential for maternal-fetal blood group incompatibility:

• If a C-negative mother carries a C-positive fetus, there is risk for alloimmunization
• Unlike Rh(D) incompatibility, routine prophylaxis for C incompatibility is not standard practice
• In the United States, cell-free DNA testing is clinically available for Rh(D) but not for c, E, and Kell antigens, though these tests are available in Europe 4

Prevention of Alloimmunization

For patients at risk of alloimmunization due to blood group incompatibilities:

• Extended red cell antigen matching (beyond just ABO and Rh D) is recommended for patients requiring chronic transfusions 4
• For pregnant women, anti-D immunoglobulin (RhIg) is given to prevent D alloimmunization, but similar prophylaxis is not routinely available for C antigen incompatibility 2

Special Considerations

• Patients with certain genetic variants may have altered expression of Rh antigens
• Patients with hybrid RHDDIIIa-CE (4-7)-D or RHCECeRN alleles, which encode partial C antigen, should receive C-negative red cells to prevent anti-C development 4
• The molecular basis for C/c specificity has been identified as an amino acid polymorphism at position 103 (Ser→Pro) 3

Understanding the prevalence and clinical significance of C negativity is important for appropriate management in both transfusion medicine and maternal-fetal medicine settings, particularly for patients requiring chronic transfusions or those at risk for hemolytic disease of the fetus and newborn.