Differential frequency of NKG2C/KLRC2 deletion in distinct African populations and susceptibility to Trachoma: a new method for imputation of KLRC2 genotypes from SNP genotyping data.
NKG2C is an activating receptor that is preferentially expressed on natural killer (NK) cells. The gene encoding NKG2C (killer cell lectin-like receptor C2, KLRC2) is present at different copy numbers in the genomes of different individuals. Deletion at the NKG2C locus was investigated in a case-control study of 1522 individuals indigenous to East- and West-Africa and the association with the ocular Chlamydia trachomatis infection and its sequelae was explored. The frequency of homozygous KLRC2 deletion was 13.7 % in Gambians and 4.7 % in Tanzanians. A significantly higher frequency of the deletion allele was found in West-Africans from the Gambia and Guinea-Bissau (36.2 % p = 2.105 × 10(-8), 26.8 % p = 0.050; respectively) in comparison to East-African Tanzanians where the frequency of the deletion is comparable to other human populations (20.9 %). We found no evidence for an association between the numbers of KLRC2 gene copies and the clinical manifestations of trachoma (follicular trachoma or conjunctival scarring). A new method for imputation of KLRC2 genotypes from single nucleotide polymorphism (SNP) data in 2621 individuals from the Gambia further confirmed these results. Our data suggest that NKG2C does not play a major role in trachomatous disease. We found that the deletion allele is present at different frequencies in different populations but the reason behind these differences is currently not understood. The new method offers the potential to use SNP arrays from genome wide association studies to study the frequency of KLRC2 deletion in other populations and its association with other diseases.
Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
Adriana
A
Goncalves
Disease Control and Elimination Theme, Medical Research Council Unit, Fajara, The Gambia.
Pateh
P
Makalo
Disease Control and Elimination Theme, Medical Research Council Unit, Fajara, The Gambia.
Hassan
H
Joof
Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.|Disease Control and Elimination Theme, Medical Research Council Unit, Fajara, The Gambia.
Sarah
S
Burr
Kilimanjaro Christian Medical Centre, Moshi, Tanzania.
Athumani
A
Ramadhani
Kilimanjaro Christian Medical Centre, Moshi, Tanzania.
Patrick
P
Massae
Kilimanjaro Christian Medical Centre, Moshi, Tanzania.
Aiweda
A
Malisa
Kilimanjaro Christian Medical Centre, Moshi, Tanzania.|International Centre for Eye Health, London School of Hygiene and Tropical Medicine, London, UK.
Tara
T
Mtuy
Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.|Kilimanjaro Christian Medical Centre, Moshi, Tanzania.
Tamsyn
T
Derrick
Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
Anna R
AR
Last
Programa Nacional de Saude de Visao, Ministerio de Saude Publica, Bissau, Guinea-Bissau.
Meno
M
Nabicassa
Programa Nacional de Saude de Visao, Ministerio de Saude Publica, Bissau, Guinea-Bissau.
Eunice
E
Cassama
Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
Joanna
J
Houghton
Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
Christine D
CD
Palmer
Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
Harry
H
Pickering
Kilimanjaro Christian Medical Centre, Moshi, Tanzania.|International Centre for Eye Health, London School of Hygiene and Tropical Medicine, London, UK.
Matthew J
MJ
Burton
Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
David C W
DC
Mabey
Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
Robin L
RL
Bailey
Department of Immunology and Infectious Disease, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
Martin R
MR
Goodier
Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.|Disease Control and Elimination Theme, Medical Research Council Unit, Fajara, The Gambia.
Martin J
MJ
Holland
Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK. Chrissy.Roberts@lshtm.ac.uk.
Chrissy H
0000-0003-1064-5980
CH
Roberts
D000293:Adolescent; D000328:Adult; D000354:Africa, Western; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017384:Sequence Deletion / Q000235:genetics; D014141:Trachoma / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology
C527059:KLRC2 protein, human; D055654:NK Cell Lectin-Like Receptor Subfamily C