Cheng-Wu Liu

Pinghua population as an exception of Han Chinese’s coherent genetic structure

AbstractThe Han Chinese is the largest single ethnic group in the world, consisting of ten Chinese branches. With the exception of the Pinghua branch, the genetic structure of this group has been studied extensively, and Y chromosome and mitochondrial (mt)DNA data have demonstrated a coherent genetic structure of all Han Chinese. It is therefore believed that the Pinghua branch, being members of an old branch of the Han Chinese, despite being scattered in and around Guangxi Province where members of the Daic and Hmong-Mien are more prevalent than Han Chinese, is no exception. We have studied 470 individual samples (including 195 males) from Pinghua populations and other ethnic groups (Zhuang, Kam, Mulam, Laka, and Mien) from six areas (Hezhou, Fuchuan, Luocheng, Jinxiu, Sanjiang, and Wuxuan) in the north of the Guangxi Zhuang Autonomous Region of China. Both mtDNA and the Y chromosomes were typed in these samples. High frequencies of the Y chromosome haplogroups O2a* and O*, which always present at a high frequency among the populations of the southern minorities, were found in Pinghua populations. Only Pinghua populations in Luocheng and Jinxiu maintain the Han frequent haplogroup O3a5a. mtDNA lineages B4a, B5a, M*, F1a, M7b1, and N* were found in Pinghua populations, exhibiting a pattern similar to the neighboring indigenous populations, especially the Daic populations. Cluster analyses (dendrograms, principal component analyses, and networks) of Pinghua populations, the other Han branches, and other ethnic groups in East Asia indicated that Pinghua populations are much closer to the southern minorities than to the other Han branches. Admixture analyses confirmed this result. In conclusion, we argue that Pinghua populations did not descend from Han Chinese, but from southern minorities. The ancestral populations of Pinghua people were assimilated by the Han Chinese in terms of language, culture, and self-identification and, consequently, the Pinghua people became an exceptional branch of Han Chineses coherent genetic structure.

Cholesteryl ester transfer protein TaqIB polymorphism and its association with serum lipid levels and longevity in Chinese Bama Zhuang population.

BackgroundTaq IB polymorphism in the cholesteryl ester transfer protein (CETP) gene has been reported to be associated with serum high-density lipoprotein cholesterol (HDL-C) levels and longevity in several populations, but controversial results also arose probably due to racial/ethnic diversity. Bama is a remote and mountainous county located in the northwest of Guangxi, Peoples Republic of China, which has been well known for its longevity for centuries. The current study was to investigate the possible association of CETP Taq IB polymorphism with serum lipid levels and longevity in the Bama Zhuang population.MethodsThe CETP Taq IB genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism in 523 long-lived inhabitants (long-lived group, LG; aged 90-107 years) and 498 healthy controls without longevity family history (non-long-lived group, non-LG; aged 40-69 years) residing in Bama County.ResultsThe levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were higher but TG, HDL-C/LDL-C ratio and the prevalence of dyslipidemia were lower in LG than in non-LG (P < 0.001 for all). There were no differences in the allelic and genotypic frequencies between the two groups (P > 0.05). Serum HDL-C levels and HDL-C/LDL-C ratio in LG were different among the genotypes (P < 0.01 for each), the subjects with B2B2 and B1B2 genotyes had higher HDL-C levels and HDL-C/LDL-C ratio than the subjects with B1B1genotye, whereas the levels of TC and HDL-C in non-LG were different among/between the genotypes (P < 0.01 for each), the B2 allele carriers had lower TC and higher HDL-C levels than the B2 allele noncarriers. Serum TG and HDL-C levels and HDL-C/LDL-C ratio were correlated with genotypes in LG, whereas serum TC and HDL-C levels were associated with genotypes in non-LG (P < 0.05-0.001).ConclusionsThe association of CETP Taq IB polymorphism and serum lipid profiles is different between LG and non-LG in the Chinese Bama Zhuang population. CETP Taq IB polymorphism might be one of the longevity-related genetic factors in this population.

ATP-binding cassette transporter G5 and G8 polymorphisms and several environmental factors with serum lipid levels.

Background The association of ATP-binding cassette (ABC) transporter single nucleotide polymorphisms (SNPs) and serum lipid profiles is inconsistent. The present study was undertaken to detect the association of ABCG5/G8 SNPs and several environmental factors with serum lipid levels. Methodology/Principal Findings Genotyping of the ABCG5 (rs4131229 and rs6720173) and ABCG8 (rs3806471 and rs4148211) SNPs was performed in 719 unrelated subjects of Mulao nationality and 782 participants of Han nationality. There were no differences in the genotypic and allelic frequencies of four SNPs between the two ethnic groups besides the genotypic frequencies of rs4131229 SNP in Han. The levels of triglyceride (TG), apolipoprotein (Apo) A1, and ApoA1/ApoB ratio (rs4131229); low-density lipoprotein cholesterol (LDL-C) and ApoB (rs6720173); high-density lipoprotein cholesterol (HDL-C), ApoA1, ApoB, and ApoA1/ApoB ratio (rs3806471); and HDL-C, ApoA1, and ApoA1/ApoB ratio (rs4148211) in Han were different among their genotypes (P<0.05–0.001). The levels of LDL-C (rs6720173) and ApoA1 (rs3806471) in Mulao were also different among their genotypes (P<0.05 for each). The levels of TC, TG, HDL-C, ApoA1, and ApoA1/ApoB ratio (rs4131229); LDL-C and ApoB (rs6720173); HDL-C, ApoA1, and ApoA1/ApoB ratio (rs3806471); and TG, HDL-C, ApoA1, and ApoA1/ApoB ratio (rs4148211) in Han males; and ApoA1/ApoB ratio (rs4131229); LDL-C, ApoB, and ApoA1/ApoB ratio (rs3806471); HDL-C, ApoA1, and ApoA1/ApoB ratio (rs4148211) in Han females were different between the genotypes (P<0.05–0.001). The levels of LDL-C in Mulao females were also different between GG and GC/CC genotypes of rs6720173 (P<0.05). The correlation between serum lipid parameters and genotypes of four SNPs was observed in Han, especially in Han males. Serum lipid parameters were also correlated with several environmental factors. Conclusions The associations of four ABCG5/G8 SNPs and serum lipid levels are different between the Mulao and Han populations, or between males and females, suggesting that there may be a racial/ethnic- and/or sex-specific association between ABCG5/G8 SNPs and some serum lipid parameters.

Association of the variants in the BUD13‐ZNF259 genes and the risk of hyperlipidaemia

The single nucleotide polymorphisms (SNPs) in the BUD13 homolog (BUD13) and zinc finger protein 259 (ZNF259) genes have been associated with one or more serum lipid traits in the European populations. However, little is known about such association in the Chinese populations. Our objectives were to determine the association of the BUD13/ZNF259 SNPs and their haplotypes with hypercholesterolaemia (HCH)/hypertriglyceridaemia (HTG) and to identify the possible gene–gene interactions among these SNPs. Genotyping of 6 SNPs was performed in 634 hyperlipidaemic and 547 normolipidaemic participants. The ZNF259 rs2075290, ZNF259 rs964184 and BUD13 rs10790162 SNPs were significantly associated with serum lipid levels in both HCH and non‐HCH populations (P < 0.008–0.001). On single locus analysis, only BUD13 rs10790162 was associated with HCH (OR: 2.23, 95% CI: 1.05, 4.75, P = 0.015). The G‐G‐A‐A‐C‐C haplotype, carrying rs964184‐G‐allele, was associated with increased risk of HCH (OR: 1.35, 95% CI: 1.10, 1.66, P = 0.005) and HTG (OR: 1.75, 95% CI: 1.39, 2.21, P = 0.000). The A‐C‐G‐G‐C‐C and A‐C‐A‐G‐T‐C haplotypes, carrying rs964184‐C‐allele, were associated with reduced risk of HCH (OR: 0.77, 95% CI: 0.61, 0.99, P = 0.039 and OR: 0.66, 95% CI: 0.47, 0.94, P = 0.021 respectively). On multifactor dimensionality reduction analyses, the two‐ to three‐locus models showed a significant association with HCH and HTG (P < 0.01–0.001). The BUD13/ZNF259 SNPs, which were significant in the European populations, are also replicable in the Southern Chinese population. Moreover, inter‐locus interactions may exist among these SNPs. However, further functional studies are required to clarify how these SNPs and genes actually affect the serum lipid levels.

Sex-specific association of rs16996148 SNP in the NCAN/CILP2/PBX4 and serum lipid levels in the Mulao and Han populations

BackgroundThe association of rs16996148 single nucleotide polymorphism (SNP) in NCAN/CILP2/PBX4 and serum lipid levels is inconsistent. Furthermore, little is known about the association of rs16996148 SNP and serum lipid levels in the Chinese population. We therefore aimed to detect the association of rs16996148 SNP and several environmental factors with serum lipid levels in the Guangxi Mulao and Han populations.MethodA total of 712 subjects of Mulao nationality and 736 participants of Han nationality were randomly selected from our stratified randomized cluster samples. Genotyping of the rs16996148 SNP was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing.ResultsThe levels of apolipoprotein (Apo) B were higher in Mulao than in Han (P < 0.001). The frequencies of G and T alleles were 87.2% and 12.8% in Mulao, and 89.9% and 10.1% in Han (P < 0.05); respectively. The frequencies of GG, GT and TT genotypes were 76.0%, 22.5% and 1.5% in Mulao, and 81.2%, 17.4% and 1.4% in Han (P < 0.05); respectively. There were no significant differences in the genotypic and allelic frequencies between males and females in both ethnic groups. The levels of HDL-C, ApoAI, and the ratio of ApoAI to ApoB in Mulao were different between the GG and GT/TT genotypes in males but not in females (P < 0.01 for all), the subjects with GT/TT genotypes had higher serum levels of HDL-C, ApoAI, and the ratio of ApoAI to ApoB than the subjects with GG genotype. The levels of TC, TG, LDL-C, ApoAI, and ApoB in Han were different between the GG and GT/TT genotypes in males but not in females (P < 0.05-0.001), the T allele carriers had higher serum levels of TC, TG, LDL-C, ApoAI, and ApoB than the T allele noncarriers. The levels of HDL-C, ApoAI, and the ratio of ApoAI to ApoB in Mulao were correlated with the genotypes in males (P < 0.05-0.01) but not in females. The levels of TC, TG, HDL-C, LDL-C, ApoAI and ApoB in Han were associated with the genotypes in males (P < 0.05-0.001) but not in females. Serum lipid parameters were also correlated with several enviromental factors in both ethnic groups (P < 0.05-0.001).ConclusionsThe genotypic and allelic frequencies of rs16996148 SNP and the associations of the SNP and serum lipid levels are different in the Mulao and Han populations. Sex (male)-specific association of rs16996148 SNP in the NCAN/CILP2/PBX4 and serum lipid levels is also observed in the both ethnic groups.

The SCARB1 rs5888 SNP and Serum Lipid Levels in the Guangxi Mulao and Han Populations

Backgroud: The associations of scavenger receptor class B type 1 (SCARB1) rs5888 single nucleotide polymorphism (SNP) and serum lipid levels are inconsistant among diverse ethnic populations. The present study was undertaken to detect the association of rs5888 SNP and serum lipid levels in the Guangxi Mulao and Han populations. Methods: Genotypes of the SCARB1 rs5888 SNP in 801 subjects of Mulao and 807 subjects of Han Chinese were determined by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. Results: Serum apolipoprotein (Apo) B levels and the T allelic frequency were higher in Mulao than in Han. Serum high-density lipoprotein cholesterol (HDL-C) levels in Mulao were different among the genotypes, the subjects with TT genotype had lower HDL-C levels than the subjects with CC or CT genotype in female (P < 0.05). For the Han population, serum triglyceride (TG), HDL-C, ApoAI, ApoB levels and the ratio of ApoAI to ApoB in males were different among the genotypes, the T allele carriers had lower serum HDL-C, ApoAI levels and ApoAI/ApoB ratio and higher serum ApoB levels than the T allele noncarriers (P < 0.05 for all), the subjects with TT genotype had higher serum TG levels than the subjects with CC or CT genotype. Serum HDL-C levels in Mulao females and serum HDL-C, ApoAI, ApoB levels and the ApoAI/ApoB ratio in Han males were correlated with genotypes by the multiple linear regression analysis. Serum lipid parameters were also influenced by genotype-environmental interactions in Han but not in Mulao populations. Conclusions: These results suggest that the rs5888 SNP is associated with serum HDL-C levels in Mulao females, and TG, HDL-C, ApoAI, ApoB levels and the ApoAI/ApoB ratio in Han males. The differences in serum ApoB levels between the two ethnic groups might partially attribute to different SCARB1 genotype-environmental interactions.

Enrichment of MTHFR 677 T in a Chinese long-lived cohort and its association with lipid modulation

BackgroundVariants in the Methylenetetrahydrofolate reductase (MTHFR) gene may result in a lowered catalytic activity and associate with subsequent elevated serum homocysteine (Hcy) concentration, abnormal DNA synthesis and methylation, cardiovascular risk, and unhealthy aging. Several investigations on the relationship of MTHFR C677T polymorphism with serum lipid profile and longevity have been conducted in some populations, but the findings remain mixed. Herein, we sought to look at the association between MTHFR C677T and lipid profile in a longevous cohort in Bama, a well-known home of longevity in China.MethodsGenotyping of MTHFR C677T was undertaken in 516 long-lived inhabitants (aged 90 and older, long-lived group, LG) and 493 healthy controls (aged 60–75, non-long-lived group, non-LG) recruited from Bama area. Correlation between MTHFR genotypes and lipids was then evaluated.ResultsT allele and TT genotype were significantly more prevalent in LG (P = 0.001 and 0.002, respectively), especially in females, than in non-LG. No difference in the tested lipid measures among MTHFR C677T genotypes was observed in LG, non-LG and total population (P > 0.05 for all). However, female but not male T carriers exhibited higher TC and LDL-C levels than did T noncarriers in the total population and in LG after stratification by sex (P < 0.05 for each). These differences did not however remain through further subdivision by hyperlipidemia and normolipidemia.ConclusionThe higher prevalence of MTHFR 677 T genotypes and its modest unfavorable impact on lipids in Bama long-lived individuals may imply an existence of other protective genotypes which require further determination.

Microsomal triglyceride transfer protein gene -493G/T polymorphism and its association with serum lipid levels in Bama Zhuang long-living families in China

BackgroundThe -493G/T polymorphism in the microsomal triglyceride transfer protein (MTP) gene is associated with lower serum low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels and longevity in several populations, but the results are inconsistent in different racial/ethnic groups. The current study was to investigate the plausible association of MTP -493G/T polymorphism with serum lipid levels and longevity in Zhuang long-lived families residing in Bama area, a famous home of longevity in Guangxi, China.MethodsThe MTP -493G/T was genotyped by PCR-restriction fragment length polymorphism in 391 Bama Zhuang long-lived families (BLF, n = 1467, age 56.60 ± 29.43 years) and four control groups recruited from Bama and out-of-Bama area with or without a familial history of exceptional longevity: Bama non-long-lived families (BNLF, n = 586, age 44.81 ± 26.83 years), Bama non-Zhuang long-lived families (BNZLF, n = 444, age 52.09 ± 31.91 years), Pingguo long-lived families (PLF, n = 658, age 50.83 ± 30.30 years), and Pingguo non-long-lived families (PNLF, n = 539, age 38.74 ± 24.69 years). Correlation analyses between genotypes and serum lipid levels and longevity were then performed.ResultsNo particularly favorable lipoprotein and clinical phenotypes were seen in BLF as compared to general families in the same area. Instead, the levels of total cholesterol (TC), TG, LDL-C, and the prevalence of dyslipidemia were significantly higher in the three Bama families as compared to the two non-Bama families (P < 0.01 for all). There were no differences in the allelic and genotypic frequencies among the tested cohorts (P > 0.05 for all), but the TT genotype tended to enrich in the three long-lived cohorts from both areas. In addition, the individuals harboring TT genotype exhibited lower LDL-C and TC levels in the overall populations and Bama populations with a region- and sex-specific pattern. Multiple linear regression analyses unraveled that LDL-C levels were correlated with genotypes in Bama combined population, BNLF, and the total population (P < 0.05 for each) but not in Pingguo populations; TC and HDL-C levels were correlated with genotypes in Bama combined population and BLF, respectively (P < 0.05 for each).ConclusionsMTP -493G/T polymorphism may play an important role in fashioning the serum lipid profiles of Bama populations, despite no direct association between MTP -493G/T and longevity was detected.

Sex-specific association of the zinc finger protein 259 rs2075290 polymorphism and serum lipid levels.

Background: Little is known about the association of ZNF259 rs2075290 single nucleotide polymorphism (SNP) and serum lipid levels in the Chinese population. This study aimed to detect the association of ZNF259 rs2075290 SNP and environmental factors with serum lipid levels between males and females in the Mulao and Han populations. Methods and Results: Genotyping of ZNF259 rs2075290 SNP was performed in 788 of Mulao and 778 of Han participants using polymerase chain reaction and restriction fragment length polymorphism. The genotype frequencies were significantly different between Mulao and Han populations (AA, 50.1% Vs 58.9%; AG, 42.3% Vs 35.7%; GG, 7.6% Vs 5.4%, P = 0.002) and between Han males and females (AA, 64.5% Vs 55.2%; AG, 28.3% Vs 40.6%; GG, 7.2% Vs 4.2%, P = 0.001). Serum levels of triglyceride (TG) in Mulao males, and total cholesterol (TC), TG and low-density lipoprotein cholesterol (LDL-C) in Mulao females were different between the AA and AG/GG genotypes (P < 0.05-0.001). Serum TC, LDL-C and apolipoprotein (Apo) A1 levels in Han males, and TG and ApoB levels and ApoA1/ApoB ratio in Han females were different between the AA and AG/GG genotypes (P < 0.05-0.001). An interaction between ZNF259 rs2075290 polymorphism and male gender on serum TC, LDL-C, and ApoA1 levels was noted in Han population (P < 0.05-0.01) but not in Mulaos. Conclusions: The subjects with AG/GG genotype in Mulao males and females and Han females have less favorable lipid profiles than those with AA genotype. In contrast, the subjects with AG/GG genotype in Han males have more favorable lipid profiles than those with AA genotype. These findings suggest that the association between ZNF259 rs2075290 SNP and serum lipid levels might have ethnic- and/or sex-specificity.

Gene flow between Zhuang and Han populations in the China-Vietnam borderland

In epidemiological studies, it is easier to glean information from isolated populations with simple genetic backgrounds than from populations with relatively complex genetic backgrounds. Regarded as an isolated population, the Minz (Hei-Yi Zhuang) in Napo County (in the China–Vietnam borderland) has been the subject of numerous recent studies. To assess the genetic isolation of this population, we studied Y chromosome and mitochondrial DNA from Minz and Han in Napo. Both populations exhibited southern Chinese genetic characteristics in both paternal and maternal lineages. Using NETWORK analyses, we found pronounced gene flow between these two populations only in maternal lineages. We also observed gene flow from other populations into the Minz gene pool. We thus concluded that the Minz is not a genetically isolated population and it is increasingly difficult to find isolated populations in mainland East Asia.