title: High prevalence of an anti-hypertriglyceridemic variant of the MLXIPL gene in Central Asia.
abstract: MLXIPL is a transcription factor integral to the regulation of glycolysis and lipogenesis in the liver. Common variants of the MLXIPL gene (MLXIPL) are known to influence plasma triglyceride levels in people of European descent. As MLXIPL has a key role in energy storage, genetic variations of the MLXIPL may be relevant to physiological adaptations to nutritional stresses that have occurred during the evolution of modern humans. In the present study, we assessed the phenotypic consequences of the Q241H variant of MLXIPL in populations of Asian and Oceanian origin and also surveyed the prevalence of Q241H variant in populations worldwide. Multiple linear regression models based on 2373 individuals of Asian origin showed that the H allele was significantly associated with decreased concentrations of plasma triglycerides (P=0.0003). Direct genotyping of 1455 individuals from Africa, Asia and Oceania showed that the triglyceride-lowering H allele was found at quite low frequencies (0.00-0.16) in most of the populations examined. The exceptions were some Central Asian populations, including Mongolians, Tibetans and Uyghurs, which exhibited much higher frequencies of the H allele (0.21-0.26). The high prevalence of the H allele in Central Asia implies that the Q241H variant of MLXIPL might have been significant for utilization of carbohydrates and fats in the common ancestors of these populations, who successfully adapted to the environment of Central Asia by relying on nomadic livestock herding.
authors.affiliation: Division of Human Genetics, Center for Molecular Medicine, Jichi Medical University, Yakushiji, Shimotsuke, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nakayama
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Yanagisawa
authors.forename: Ayumi
authors.initials: A
authors.lastname: Ogawa
authors.forename: Yuumi
authors.initials: Y
authors.lastname: Ishizuka
authors.forename: Lkhagvasuren
authors.initials: L
authors.lastname: Munkhtulga
authors.forename: Phitaya
authors.initials: P
authors.lastname: Charupoonphol
authors.forename: Somjit
authors.initials: S
authors.lastname: Supannnatas
authors.forename: Stevenson
authors.initials: S
authors.lastname: Kuartei
authors.forename: Ulziiburen
authors.initials: U
authors.lastname: Chimedregzen
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Koda
authors.forename: Takafumi
authors.initials: T
authors.lastname: Ishida
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Kagawa
authors.forename: Sadahiko
authors.initials: S
authors.lastname: Iwamoto
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001209:Asia, Central / Q000453:epidemiology; D044466:Asian People / Q000235:genetics; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D015228:Hypertriglyceridemia / Q000453:epidemiology / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D014280:Triglycerides / Q000097:blood*; D055815:Young Adult
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C116385:MLXIPL protein, human; D014280:Triglycerides