TY - JOUR
T1 - Variation of the McKusick-Kaufman gene and studies of relationships with common forms of obesity
AU - Andersen, Kirstine L.
AU - Echwald, Søren M.
AU - Larsen, Lesli H.
AU - Hamid, Yasmin H.
AU - Glümer, Charlotte
AU - Jørgensen, Torben
AU - Borch-Johnsen, Knut
AU - Andersen, Teis
AU - Sørensen, Thorkild I.A.
AU - Hansen, Torben
AU - Pedersen, Oluf
PY - 2005/1/1
Y1 - 2005/1/1
N2 - Obesity is a prominent feature of the Bardet-Biedl syndrome (BBS), one subset of which, BBS6, is due to mutations in the chaperonin-like gene termed the McKusick-Kaufman syndrome (MKKS) gene. We tested whether variation in MKKS contributes to common and probably polygenic forms of obesity by performing mutation analysis of the coding region in 60 Danish white men with juvenile-onset obesity. Five variants were identified, including two synonymous mutations (Pro39Pro and Ile178Ile) and three nonsynonymous variants (Ala242Ser, Arg517Cys, and Gly 532Val). Furthermore, the rare Ala242Ser was identified in two families and showed partial cosegregation with obesity. The Pro 39Pro, Ile178Ile, and Arg517Cys variants are in complete linkage disequilibrium and defined a prevalent haplotype. In a case-control study, the Arg517Cys polymorphism allele prevalence was 11.4% [95% confidence interval (CI), 9.7-13.0] among 744 men with juvenile-onset obesity and 9.3% (CI, 7.9-10.7) among 867 control subjects (P = 0.048). However, among middle-aged men the allelic prevalence was 9.7% (CI, 7.9-11.4) among 523 obese men and 12.2% (CI, 10.8-13.6) among 1051 lean men (P = 0.037). In conclusion, it is unlikely that MKKS variants play a major role in the pathogenesis of nonsyndromic obesity, although in rare cases the A242S allele may contribute to obesity.
AB - Obesity is a prominent feature of the Bardet-Biedl syndrome (BBS), one subset of which, BBS6, is due to mutations in the chaperonin-like gene termed the McKusick-Kaufman syndrome (MKKS) gene. We tested whether variation in MKKS contributes to common and probably polygenic forms of obesity by performing mutation analysis of the coding region in 60 Danish white men with juvenile-onset obesity. Five variants were identified, including two synonymous mutations (Pro39Pro and Ile178Ile) and three nonsynonymous variants (Ala242Ser, Arg517Cys, and Gly 532Val). Furthermore, the rare Ala242Ser was identified in two families and showed partial cosegregation with obesity. The Pro 39Pro, Ile178Ile, and Arg517Cys variants are in complete linkage disequilibrium and defined a prevalent haplotype. In a case-control study, the Arg517Cys polymorphism allele prevalence was 11.4% [95% confidence interval (CI), 9.7-13.0] among 744 men with juvenile-onset obesity and 9.3% (CI, 7.9-10.7) among 867 control subjects (P = 0.048). However, among middle-aged men the allelic prevalence was 9.7% (CI, 7.9-11.4) among 523 obese men and 12.2% (CI, 10.8-13.6) among 1051 lean men (P = 0.037). In conclusion, it is unlikely that MKKS variants play a major role in the pathogenesis of nonsyndromic obesity, although in rare cases the A242S allele may contribute to obesity.
UR - http://www.scopus.com/inward/record.url?scp=19944429511&partnerID=8YFLogxK
U2 - 10.1210/jc.2004-0465
DO - 10.1210/jc.2004-0465
M3 - Article
C2 - 15483080
AN - SCOPUS:19944429511
VL - 90
SP - 225
EP - 230
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 1
ER -