The SLC6A14 gene shows evidence of association with obesity.
In our previous genome-wide scan of Finnish nuclear families, obesity was linked to chromosome Xq24. Here we analyzed this 15-Mb region by genotyping 9 microsatellite markers and 36 single nucleotide polymorphisms (SNPs) for 11 positional and functional candidate genes in an extended sample of 218 obese Finnish sibling pairs (sibpairs) (BMI > 30 kg/m2). Evidence of linkage emerged mainly from the obese male sibpairs, suggesting a gender-specific effect for the underlying gene. By constructing haplotypes among the obese male sibpairs, we restricted the region from 15 Mb to 4 Mb, between markers DXS8088 and DXS8067. Regional functional candidate genes were tested for association in an initial sample of 117 cases and 182 controls. Significant evidence was observed for association for an SNP in the 3'-untranslated region of the solute carrier family 6 member 14 (SLC6A14) gene (P = 0.0002) and for SNP haplotypes of the SLC6A14 gene (P = 0.0007-0.006). Furthermore, an independent replication study sample of 837 cases and 968 controls from Finland and Sweden also showed significant differences in allele frequencies between obese and non-obese individuals (P = 0.003). The SLC6A14 gene is an interesting novel candidate for obesity because it encodes an amino acid transporter, which potentially regulates tryptophan availability for serotonin synthesis and thus possibly affects appetite control.
Suviolahti
Elina
E
Department of Human Genetics, University of California, Los Angeles, USA.
Oksanen
Laura J
LJ
Ohman
Miina
M
Cantor
Rita M
RM
Ridderstrale
Martin
M
Tuomi
Tiinamaija
T
Kaprio
Jaakko
J
Rissanen
Aila
A
Mustajoki
Pertti
P
Jousilahti
Pekka
P
Vartiainen
Erkki
E
Silander
Kaisa
K
Kilpikari
Riika
R
Salomaa
Veikko
V
Groop
Leif
L
Kontula
Kimmo
K
Peltonen
Leena
L
Pajukanta
Päivi
P
D000328:Adult; D000368:Aged; D000483:Alleles; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000502:physiology; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012727:Sex Characteristics
D005819:Genetic Markers; D026901:Membrane Transport Proteins